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## Protocol Section ### Identification Module **NCT ID:** NCT03998579 **Acronym:** CanMoRe **Brief Title:** Physical Rehabilitation Among Patients Undergoing Radical Cystectomy Due to Urinary Bladder Cancer **Official Title:** The Effect of Physical Rehabilitation Among Patients Undergoing Radical Cystectomy Due to Urinary Bladder Cancer - the CanMoRe Study #### Organization Study ID Info **ID:** 2012/2214-31/4 #### Organization **Class:** OTHER **Full Name:** Karolinska Institutet ### Status Module #### Completion Date **Date:** 2023-06-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-11 **Type:** ACTUAL **Last Update Submit Date:** 2023-10-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-11-15 **Type:** ACTUAL #### Start Date **Date:** 2019-09-01 **Type:** ACTUAL **Status Verified Date:** 2023-10 #### Study First Post Date **Date:** 2019-06-26 **Type:** ACTUAL **Study First Submit Date:** 2019-06-07 **Study First Submit QC Date:** 2019-06-25 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Karolinska University Hospital #### Lead Sponsor **Class:** OTHER **Name:** Karolinska Institutet #### Responsible Party **Investigator Affiliation:** Karolinska Institutet **Investigator Full Name:** Maria Hagströmer **Investigator Title:** Associate professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The main objective of the CanMoRe study is to evaluate the impact of a standardized and individually adapted exercise intervention in Primary Health Care aiming at improving physical function (primary outcome) and habitual physical activity, health related quality of life, fatigue and psychological well-being in patients undergoing radical cystectomy due to urinary bladder cancer. **Detailed Description:** The most common treatment for solid cancer tumours is surgery, often in combination with chemo- and/or radiotherapy. To minimise the postoperative complications is important in today's health care. Early mobilisation at the ward and physical activity at home after discharge, have been shown to be important parts to reduce complications. Common complications after abdominal surgery are postoperative pulmonary complications and venous thrombosis. One of the conditions that suffers the most from different kinds of postoperative complications is radical cystectomy due to urinary bladder cancer. Complications after radical cystectomy could be direct related to the patients' high age and also high degree of comorbidity. There is today strong evidence that physical activity has a positive impact on health, survival and quality of life. Patients who have been treated for urinary bladder cancer are not sufficiently physical active and suffer from readmissions to hospital due to complications. Therefore, there is a need for developing and testing a physical rehabilitation programme to support patients who have a radical cystectomy, in the early postoperative period. The CanMoRe study is a randomized controlled trial with a single-blinded design evaluating an exercise intervention in Primary Health Care as part of the CanMoRe programme. In addition, a qualitative study (interviews) on patient's experience of the programme will be conducted as well as data gathered on factors that might influence the implementation of the programme. Then CanMoRe programme consists of preoperative information, the Activity Board used for enhanced mobilization during hospital stay, a 12-week, (1 h, 2 times/week) standardized and individually adapted exercise intervention in Primary Health Care and behavioral support for daily physical activity. The CanMoRe programme is evaluated in two steps, i.e. the in-hospital intervention using the Activity Board (published) and the exercise intervention in Primary Health Care reported herein. ### Conditions Module **Conditions:** - Urinary Bladder Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The intervention group get a referral to physiotherapist in Primary Health Care in Stockholm County Council, close to where they live. Within the third week after discharge, the patients begin twelve weeks of biweekly exercise. The physical exercise is individually targeted aerobic and strength exercises, based on international recommendations for persons with cancer disease. The program is approved by resposible surgeons. **Intervention Names:** - Other: The CanMoRe programme **Label:** Individualized exercise **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Oral and written information of a home-based exercise programme and information of supportive techniques to improve physical activity **Intervention Names:** - Other: Home exercise **Label:** Active control group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Individualized exercise **Description:** An exercise intervention in Primary Health Care **Name:** The CanMoRe programme **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Active control group **Description:** An active control group **Name:** Home exercise **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The test reproduces activity of daily living at a sub maximal level. Output: meters Score: 0-900. **Measure:** Six-minute walk test **Time Frame:** Change from baseline to after 12 weeks intervention #### Secondary Outcomes **Description:** Habitual physical activity, measured for 7 consecutive days. Output: number of steps per day. **Measure:** ActivPAL accelerometer **Time Frame:** Measurement 1: Baseline, Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge **Description:** Measure of leg strength. Output: Scale 0-30 **Measure:** Chair stand test **Time Frame:** Measurement 1: Baseline, Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge **Description:** Measure of hand grip strength (Jamar hand dynamometer). Output: Kilo 0-60 **Measure:** Hand grip strength **Time Frame:** Measurement 1: Baseline, Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge, **Description:** Health related quality of life. Output: Scale 0-100. A higher score is worse outcome. For more information see https://qol.eortc.org/questionnaires/ **Measure:** European Organisation for Research and Treatment of Cancer (EORTC) Quality of life for cancer patients QLQ-C30 **Time Frame:** Measurement 1: Baseline Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge **Description:** Health related quality of life specific for bladder cancer Output: Scale 0-100, a higher score is worse **Measure:** EORTC QLQ-BLM30 **Time Frame:** Measurement 1: Baseline Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge **Description:** Fatigue. Output: Scale 0-10. A higher score is worse, i.e more fatigue **Measure:** Piper Fatigue Scale **Time Frame:** Measurement 1: Baseline, Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge **Description:** Pain. Output: Scale 0-10, A higher score is worse i.e more pain **Measure:** Numeric rating scale (NRS) **Time Frame:** Measurement 1: Baseline, Measurement 2: After 12 weeks intervention. Measurement 3: 1 year after discharge **Description:** Psychological wellbeing. Output: Scale 0-21. A higher score is worse **Measure:** Hospital Anxiety and Depression Scale (HADS) **Time Frame:** Measurement 1: Baseline, Measurement 2: 12 weeks. Measurement 3: 1 year after discharge **Description:** Readmissions to hospital. Output: Yes/No **Measure:** Readmission **Time Frame:** Collected from journals using standardized time frames at 30 and 90 days **Description:** Complications such as Pneumonia Output: according to Clavien - Dindo classification **Measure:** Complications **Time Frame:** Collected from journals using standardized time frames at 30 and 90 days **Description:** The test reproduces activity of daily living at a sub maximal level. Output: meters Score: 0-900. **Measure:** Six-minute walk test **Time Frame:** Measurement 3: 1 year after discharge ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who are planned for a robotic assisted laparoscopic radical cystectomy due to urinary bladder cancer at the Karolinska University Hospital Solna will be included in the trial. The patients should be able to talk and understand Swedish, live in the Stockholm County Council area and be mobile with or without walking aid. Exclusion Criteria: * Patients who will undergo radical cystectomy on a non-curative basis will not be included. **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Stockholm **Country:** Sweden **Facility:** Karolinska University Hospital **Zip:** 17176 #### Overall Officials **Official 1:** **Affiliation:** Karolinska Institutet **Name:** Maria Hagstromer, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Porserud A, Karlsson P, Rydwik E, Aly M, Henningsohn L, Nygren-Bonnier M, Hagstromer M. The CanMoRe trial - evaluating the effects of an exercise intervention after robotic-assisted radical cystectomy for urinary bladder cancer: the study protocol of a randomised controlled trial. BMC Cancer. 2020 Aug 26;20(1):805. doi: 10.1186/s12885-020-07140-5. **PMID:** 32842975 #### See Also Links **Label:** The link to the larger project to which this RCT belong **URL:** https://ki.se/en/nvs/the-abdmore-project-2016-2020 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014571 - Term: Urologic Neoplasms - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000001745 - Term: Urinary Bladder Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5030 - Name: Urinary Bladder Neoplasms - Relevance: HIGH - As Found: Urinary Bladder Cancer - ID: M17320 - Name: Urologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M5026 - Name: Urinary Bladder Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001749 - Term: Urinary Bladder Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01095679 **Acronym:** PERIODIBAC **Brief Title:** Baclofen and Hypoxia-induced Periodic Ventilation **Official Title:** Assessment of the Effect of the GABA-B Receptor Agonist, Baclofen, on Hypoxia-induced Periodic Ventilation, in Healthy Subjects #### Organization Study ID Info **ID:** P090207 #### Organization **Class:** OTHER **Full Name:** Assistance Publique - Hôpitaux de Paris ### Status Module #### Completion Date **Date:** 2011-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-10-31 **Type:** ESTIMATED **Last Update Submit Date:** 2012-10-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-09 **Type:** ACTUAL #### Start Date **Date:** 2010-03 **Status Verified Date:** 2009-12 #### Study First Post Date **Date:** 2010-03-30 **Type:** ESTIMATED **Study First Submit Date:** 2010-03-29 **Study First Submit QC Date:** 2010-03-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assistance Publique - Hôpitaux de Paris #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Periodic ventilation that includes CHEYNE Stokes ventilation is a pathological pattern characterized by alternating periods of hyperpneas and apnea-hypopneas. It occurs generally during sleep, at high altitude and in hypoxic conditions in healthy subjects, and in some diseases like congestive heart failure. One study conducted on an animal model suggested that baclofen, a drug already used against spasticity in humans, could also be effective against periodic ventilation. The goal of the study is therefore to assess this hypothesis on hypoxia-induced periodic ventilation in healthy subjects during sleep. **Detailed Description:** Rationale of the study: Periodic ventilation, often called CHEYNE Stokes ventilation, results from a dysfunction of the mechanisms of the control of breathing. In this type of ventilation, alternating periods of hyperventilation and apneas and/or hypoventilation replace the normal regular pattern of breathing. Periodic ventilation occurs preferentially during sleep. It is responsible for decreases in arterial saturation in oxygen and for sleep fragmentation. There is currently no consensual treatment but non-invasive nocturnal mechanical ventilation is often used to bring the ventilatory pattern back to normal. Periodic ventilation occurs in various conditions, the most frequent being cardiac failure. It also occurs in healthy subjects exposed to hypoxia or at high altitude. The pathophysiology of periodic breathing remains poorly understood. Our hypothesis regarding the mechanisms of this abnormal ventilatory pattern is based on comparative physiology. Periodic ventilation is indeed the usual ventilatory pattern of many lower vertebrates. Moreover, even isolated in VITRO, the tadpole brainstem still produces a periodic ventilatory rhythm, characterized by clusters of ventilatory discharges. In this model, the agonist of the GABA-B receptor, the baclofen, transforms the periodic pattern into a regular one. Of note, the baclofen is already used in the treatment of some human diseases, especially against spasticity. The hypothesis of the research project assumes that periodic ventilation in humans results from a neural reconfiguration of the networks that command breathing, leading them to produce an ancestral behavior. It also assumes that the baclofen woul reverse this phenomenon as it does in the model of the tadpole isolated brainstem. The goal of the project is therefore to assess the effect of baclofen on hypoxia-induced periodic ventilation in healthy subjects during sleep. This is thus a pathophysiological study that aimed at demonstrating a concept before a possible clinical trial. This study is pathophysiological study, conducted in healthy volunteers only. Methods: The subjects will sleep in hypoxic conditions, with a level of hypoxia similar to the one that is found at an altitude of 4000-4500 meters. A this altitude, the partial pressure of oxygen is approximately 90-100 mmHg. The hypoxic atmosphere will be created in a tent with an hypoxic generator (EVEREST Summit Hypoxic Generator, Hypoxic Systems, New York, NY, USA). The electroencephalographic and electrocardiographic signals and the movements of the chest and of the abdomen will be recorded with a portable polysomnograph. The electromyogram of the chin and the ELECTRO Oculogram will also be recorded. These signals will permit to identify the sleep stages. The subjects will ware a face mask connected to a pneumotachometer for the recording of the ventilatory flow. Gas will also be sampled to measure the end tidal partial pressure of CO2. Protocol: Healthy volunteers will be enrolled after they will have given written informed consent. The subjects will be asked about their medical history and physical examination will be performed. Chest X-ray, electrocardiogram and pulmonary function tests will also be performed. The subject will be asked not to sleep the night before each recording in hypoxic conditions (the hypoxic sessions). The recordings will be performed either during a nap in the afternoon or at night. A first hypoxic session will be performed to identify the subjects who will develop periodic ventilation. Only those who will exhibit periodic ventilation during sleep will continue the study. They will be prescribed either baclofen or placebo (double blind, randomized). The posology will be progressively increased (over approximately 10 days) to reach 20 mg 3 times a day, during 3 to 5 days. A second hypoxic session will be performed under this treatment. Then the posology will be decreased over 3 days and a complete weaning will be performed during 5 to 10 days. The same protocol will be repeated, either with baclofen or placebo (depending of the previous run) and a third hypoxic session will be performed. The posology will then be decreased over 3 days and the study will be considered ended for the subject after 2 more days of complete weaning. The maximum duration of the study for one subject will be 63 days. ### Conditions Module **Conditions:** - CHEYNE Stokes Respiration **Keywords:** - CHEYNE Stokes respiration - Periodic ventilation - baclofen - hypoxia - healthy subject ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 53 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Baclofen **Label:** Baclofen **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Baclofen **Description:** Breaking tablets of 10 mg of baclofen. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day. **Name:** Baclofen **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Breaking tablets of 10 mg of placebo. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day. **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The primary outcome will be the decrease in the coefficient of variation of the period of the ventilatory cycle. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Decrease in the coefficient of variation of the period of the ventilatory cycle **Time Frame:** During the second and the third session in hypoxia #### Secondary Outcomes **Description:** Decrease in the coefficient of variation of the tidal volume. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Decrease in the coefficient of variation of the tidal volume **Time Frame:** During the second and the third session in hypoxia **Description:** Decrease in the coefficient of variation of the end tidal CO2 pressure. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Decrease in the coefficient of variation of the end tidal CO2 pressure **Time Frame:** During the second and the third session in hypoxia **Description:** Decrease in the number of frequency compounds of the ventilatory flow. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Decrease in the number of frequency compounds of the ventilatory flow **Time Frame:** During the second and the third session in hypoxia **Description:** Decrease in the apnea-hypopnea index. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Decrease in the apnea-hypopnea index **Time Frame:** During the second and the third session in hypoxia **Description:** Decrease in the sleep fragmentation index. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Decrease in the sleep fragmentation index **Time Frame:** During the second and the third session in hypoxia **Description:** Change in the non-linea dynamics of the ventilatory flow. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days. **Measure:** Change in the non-linea dynamics of the ventilatory flow **Time Frame:** During the second and the third session in hypoxia ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult * Male * Body mass index between 20 and 30 kg/m2 * Healthy (no known disease) * No regular treatment except first grade antalgic drugs (e. g. ACETAMINOFEN) * Written consent to participate in the study * Health insurance Exclusion Criteria: * Intolerance to baclofen * Tobacco, alcohol or drug consumption * Past history of possible acute mountain sickness * Regular treatment for any disease * Claustrophobia * Coronary disease * Hypertension * Cardiac failure * Cardiac rhythm abnormalities * Pulmonary hypertension * Any pulmonary artery abnormality * Any cardiac disease * Past history of cerebral ischemia * Past history of psychiatric disorder * Any respiratory disease (including asthma) * Leg arteriopathy * Sickle cell anemia * Renal insufficiency * Migraine * Diabetes * Obesity * Thalassemia * Scoliosis * Past history of phlebitis **Healthy Volunteers:** True **Maximum Age:** 35 Years **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Paris **Country:** France **Facility:** Pitié-Salpêtrière Hospital **Zip:** 75013 #### Overall Officials **Official 1:** **Affiliation:** Assistance Publique - Hôpitaux de Paris **Name:** Christian Straus, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012818 - Term: Signs and Symptoms, Respiratory - ID: D000012120 - Term: Respiration Disorders - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M4185 - Name: Hypoxia - Relevance: HIGH - As Found: Hypoxia - ID: M5884 - Name: Cheyne-Stokes Respiration - Relevance: HIGH - As Found: Cheyne-Stokes Respiration - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002639 - Term: Cheyne-Stokes Respiration - ID: D000000860 - Term: Hypoxia ### Intervention Browse Module - Ancestors - ID: D000009125 - Term: Muscle Relaxants, Central - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000009465 - Term: Neuromuscular Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000058786 - Term: GABA-B Receptor Agonists - ID: D000018755 - Term: GABA Agonists - ID: D000018682 - Term: GABA Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: MuRelCen - Name: Muscle Relaxants, Central - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4716 - Name: Baclofen - Relevance: HIGH - As Found: Aspart - ID: M20825 - Name: GABA Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000001418 - Term: Baclofen ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05385679 **Brief Title:** Comparison of Two Flaps in Surgical Removal of Impacted Lower Third Molar **Official Title:** Comparison of Two Flaps in Surgical Removal of Impacted Lower Third Molar;a Randomized Comparative Double Blind Study #### Organization Study ID Info **ID:** IOM2 #### Organization **Class:** OTHER **Full Name:** College of Medical Sciences Teaching Hospital. Nepal ### Status Module #### Completion Date **Date:** 2023-03-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-13 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-09 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2023-03-02 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-01 **Type:** ESTIMATED **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2022-05-23 **Type:** ACTUAL **Study First Submit Date:** 2022-05-12 **Study First Submit QC Date:** 2022-05-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ashutosh Kumar Singh #### Responsible Party **Investigator Affiliation:** College of Medical Sciences Teaching Hospital. Nepal **Investigator Full Name:** Ashutosh Kumar Singh **Investigator Title:** Lecturer of department Oral And Maxillofacial Surgery **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Project summary The surgical removal of mandibular third molar is one of the most common procedures done in oral and maxillofacial surgery. Patients often experience pain, swelling, trismus, dehiscence, alveolar osteitis, infection, nerve injury and periodontal tissue damage after third molar surgery. Flap design is an important step in third molar surgery.The aim of this study is to compare the triangular and envelope flap designs in lower third molar surgery in terms of postoperative sequelae including pain ,trismus,swelling,incidence of dry socket and also operative time taken.The study also aims to find out does the level of impacted mandibular third molar and number of roots has effect on postoperative outcomes in surgical removal of mandibular third molar.The study design used will be a double-blind randomized clinical study. Patients who fit the inclusion criteria will be included as research subjects.Sample will be divided into two groups randomly. In one group the envelope flap will be raised during surgical removal of the lower third molar while in the other triangular flap will be used. Investigators will also divide the third molars into level 1,level 2,level 3 based on the relationship between the tip of mesial cusp of impacted third molar and the distal surface of crown of adjacent second molar based on orthopantomograph findings.Level 1 will be when the tip of mesial cusp of third molar is within the occlusal third of crown of second molar,level 2 will be when the tip of mesial cusp of third molar is within the middle third of crown of second molar, level 3 will be when the tip of mesial cusp of third molar is within and below the cervical third of crown of second molar. Another subgroup will be based on the number of roots of the impacted third molar where investigators will divide the third molar into single rooted and multirooted based on orthopantomograph findings. Investigators will also divide the sample based on gender and age group as below 30 years and above 30 years. The primary outcomes to be measured are pain and operative time while secondary outcomes are swelling ,trismus and incidence of dry socket.Outcome assessment will be done by another clinician than surgeon using scientific tools and techniques as mentioned. Surgical procedures and outcomes measurement will be done by separate clinicians to ensure masking. **Detailed Description:** Andreasen et al (1997) defines impaction as a cessation of the eruption of a tooth caused by a clinically or radiographically detectable physical barrier in the eruption path or by an ectopic position of the tooth. The prevalence of third molar impaction ranges from 16.7% to 68.6%. Common pathologies associated with third molars are pericoronitis, caries of impacted teeth or adjacent tooth, second molar tooth resorption, periodontal bone loss of adjacent tooth and odontogenic cysts. The surgical removal of mandibular third molar is one of the most common procedures done in oral and maxillofacial surgery. Flap design is an important step in third molar surgery.Commonly used flap in surgical removal of third molar are envelope flap and triangular flap with modifications. A number of classifications have been developed for impacted third molars.The most widely used are; 1. Angulation (Winter, 1926) of the impacted tooth ; Vertical, Mesioangular, Horizontal, Distoangular 2. Relationship of the impacted tooth to the anterior border of the ramus (Pell and Gregory, 1942); Class I: Sufficient space available anterior to the anterior border of ramus for the third molar to erupt. Class II: Space available is less than the mesio distal width of the crown of the third molar Class III: All or most of the third molar is located within the ramus. 3. Depth of impaction (Pell and Gregory Classification based on relationship to occlusal plane); Position A: The highest portion of the tooth (occlusal plane) is on a level with or above the occlusal line. Position B: The highest portion of the tooth is below the occlusal line but above the cervical line of the second molar. Position C: The highest portion of the tooth is below the cervical line of the second molar. Rationale and justifications of study The surgical removal of mandibular third molar is one of the most common procedure done in oral and maxillofacial surgery and often associated with pain, swelling, trismus, dehiscence, alveolar osteitis, infection, nerve injury and periodontal tissue damage.Flap design is an important step in this procedure. The present study is aimed at comparing the envelope and triangular flap in lower third molar surgery based on postoperative outcomes.The study also aims to find does the number of roots and also the relation between level of mesial cusp tip of impacted lower third molar and distal surface of adjacent second molar has any effect on postoperative sequelae. Although much research was done so far on this topic,further studies were suggested . Both envelope and triangular flaps are routinely used in lower third molar surgery.So,this study claims no extra medical risks related to the intervention.Patients and investigators bear no extra economic burden in investigations and research. Objectives General: To compare the triangular and envelope flap in surgical removal of vertical and mesioangular impacted lower third molar. Specific: To evaluate whether the relation between level of mesial cusp tip of impacted third molar to the distal surface of adjacent second molar has any effect on the post operative outcomes independent of flap designs. To evaluate the effect of the number of roots of impacted third molar to the postoperative outcomes in third molar surgery independent of flap designs. Research hypothesis Null hypothesis: There is no difference between the envelope and triangular flap in terms of post operative outcomes in surgical removal of vertical and mesioangular impacted mandibular third molar. Alternate hypothesis:There is significant difference between envelope and triangular flap in terms of post operative outcomes in surgical removal of vertical and mesioangular impacted mandibular third molar. Research design and methodology Research method Quantitative Type of study Experimental, double blinded, randomized comparaive study, Study population Patient visiting department of oral and maxillofacial surgery in TUTH Study site and its justification Large number of patients visit oral surgery department in TUTH.Most of them visit for surgical removal of impacted mandibular third molar and surgical extraction is commonly performed here.So oral and maxillofacial surgery OPD of TUTH will be ideal site for study as adequate sample size will be available without economic burden to the patient and investigator. Sampling method Sampling method :Simple random sampling Randomisation will be done by random draw computer method Allocation concealment will be maintained using a sealed opaque envelope. Sample size Sample size will be calculated as; Sample size=2SD2(Z ### Conditions Module **Conditions:** - Impacted Third Molar Tooth ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 70 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** An envelope flap designs involves a sulcular incision from the first to the second molar and a distal relieving incision to the mandibular ramus. **Intervention Names:** - Procedure: Surgical Extraction of lower third molar **Label:** Envelop Flap **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Triangular flap involves incision from the mandibular ramus to the distobuccal crown edge of the second molar, followed by a perpendicular incision obliquely into the mandibular vestibulum, with a length of about 10 mm. **Intervention Names:** - Procedure: Surgical Extraction of lower third molar **Label:** Triangular flap **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Envelop Flap - Triangular flap **Description:** The surgical removal of mandibular third molar is one of the most common procedures done in oral and maxillofacial surgery. Patients often experience pain, swelling, trismus, dehiscence, alveolar osteitis, infection, nerve injury and periodontal tissue damage after third molar surgery. Flap design is an important step in third molar surgery. Envelope flap and modifications of triangular flap are the two most commonly used flaps in surgical removal of lower third molar. **Name:** Surgical Extraction of lower third molar **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The operative time taken will be recorded from the point of incision to the point of last suturing in terms of minutes. **Measure:** operative time taken for the surgical removal of impacted lower third molar **Time Frame:** immediately after surgery **Description:** The postoperative pain will be measured by the visual analogue pain scale grading from 0 to 10 where score of 0 means no pain and 10 means maximum pain that can be felt by patient. **Measure:** postoperative pain Post operative pain which will be measured based on the questionnaires on defined post operative days **Time Frame:** 1st postoperative day **Description:** The postoperative pain will be measured by the visual analogue pain scale grading from 0 to 10 where score of 0 means no pain and 10 means maximum pain that can be felt by patient. **Measure:** postoperative pain Post operative pain which will be measured based on the questionnaires on defined post operative days **Time Frame:** 3rd postoperative day **Description:** The postoperative pain will be measured by the visual analogue pain scale grading from 0 to 10 where score of 0 means no pain and 10 means maximum pain that can be felt by patient. **Measure:** postoperative pain Post operative pain which will be measured based on the questionnaires on defined post operative days **Time Frame:** 7th postoperative day #### Secondary Outcomes **Description:** Measurement of edema will be done by using three facial lines ie. the tragus distance (point A) to the corner of the mouth (point C) , the tragus distance (point A) to pogonion (point D) and the angular distance (point E) to the lateral angle of the eye (point B). The distance between the three lines is measured in length and the average value is measured. Swelling will be measured as the difference between pre and post operative distance between these points in terms of millimeters. **Measure:** postoperative swelling **Time Frame:** 1st postoperative day **Description:** Measurement of edema will be done by using three facial lines ie. the tragus distance (point A) to the corner of the mouth (point C) , the tragus distance (point A) to pogonion (point D) and the angular distance (point E) to the lateral angle of the eye (point B). The distance between the three lines is measured in length and the average value is measured. Swelling will be measured as the difference between pre and post operative distance between these points in terms of millimeters. **Measure:** postoperative swelling **Time Frame:** 3rd postoperative day **Description:** Measurement of edema will be done by using three facial lines ie. the tragus distance (point A) to the corner of the mouth (point C) , the tragus distance (point A) to pogonion (point D) and the angular distance (point E) to the lateral angle of the eye (point B). The distance between the three lines is measured in length and the average value is measured. Swelling will be measured as the difference between pre and post operative distance between these points in terms of millimeters. **Measure:** postoperative swelling **Time Frame:** 7th postoperative day **Description:** Trismus will be measured as the difference in the distance between the incisal edge of the maxillary central incisor to the lower incisor in midline before and after surgery by using vernier caliper in terms of millimeters. **Measure:** post operative trismus **Time Frame:** 1st postoperative day **Description:** Trismus will be measured as the difference in the distance between the incisal edge of the maxillary central incisor to the lower incisor in midline before and after surgery by using vernier caliper in terms of millimeters. **Measure:** post operative trismus **Time Frame:** 3rd postoperative day **Description:** Trismus will be measured as the difference in the distance between the incisal edge of the maxillary central incisor to the lower incisor in midline before and after surgery by using vernier caliper in terms of millimeters. **Measure:** post operative trismus **Time Frame:** 7th postoperative day **Description:** The occurrence of dry socket will be observed by looking at whether there is an open alveolar bone area and the patient complaining of postoperative pain. **Measure:** dry socket **Time Frame:** 3rd postoperative day **Description:** The occurrence of dry socket will be observed by looking at whether there is an open alveolar bone area and the patient complaining of postoperative pain **Measure:** dry socket **Time Frame:** 7th postoperative day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age between 18-50 years * No systemic illness and not taking any regular medications * No signs of local inflammation * Mesioangular and vertically impacted lower third molar * Not under antibiotics for at least 3 days before surgery Exclusion Criteria: * With known systemic illness * Those taking regular medications * Presenting with pain and swelling at the time of surgery * Impactions other than mesioangular and vertical impactions of lower third molar * Under antibiotics within 3 days of surgical procedure * Those having habit of cigarette smoking and females taking oral contraceptives **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014076 - Term: Tooth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M16850 - Name: Tooth, Impacted - Relevance: HIGH - As Found: Impacted - ID: M16831 - Name: Tooth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014095 - Term: Tooth, Impacted ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00362479 **Brief Title:** Open-Label Study to Evaluate the Safety and Efficacy of a Low-Dose 28-Day Oral Contraceptive **Official Title:** A Prospective, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of the 28-Day Oral Contraceptive DR-1021 #### Organization Study ID Info **ID:** DR-DSG-301 #### Organization **Class:** INDUSTRY **Full Name:** Teva Branded Pharmaceutical Products R&D, Inc. ### Status Module #### Completion Date **Date:** 2007-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-08-21 **Type:** ESTIMATED **Last Update Submit Date:** 2013-08-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-07 **Type:** ACTUAL #### Start Date **Date:** 2006-08 **Status Verified Date:** 2013-08 #### Study First Post Date **Date:** 2006-08-10 **Type:** ESTIMATED **Study First Submit Date:** 2006-08-09 **Study First Submit QC Date:** 2006-08-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Duramed Research #### Responsible Party **Old Name Title:** Duramed Protocol Chair **Old Organization:** Duramed Research, Inc. ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an open-label, single treatment study. All subjects will receive 6 months of oral contraceptive therapy with DR-1021. Study participants will receive physical and gynecological exams, including Pap smear. During the study, all participants will be required to complete a diary. **Detailed Description:** The overall study duration for each patient will be approximately 8 months, which includes a screening period of approximately 4 weeks; a treatment period of approximately six months (six,28-day cycles); and a follow-up visit approximately 4 weeks after completion of study drug. ### Conditions Module **Conditions:** - Contraception **Keywords:** - pregnancy prevention - oral contraceptives ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 1347 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: DR-1021 **Label:** 1 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** 1 tablet daily **Name:** DR-1021 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Evaluation of pregnancy rates **Time Frame:** Duration of study #### Secondary Outcomes **Measure:** Adverse events reported by patients and investigators **Time Frame:** Duration of study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Premenopausal * Not pregnant or breastfeeding * Sexually active at risk of pregnancy Exclusion Criteria: * Any contraindication to the use of oral contraceptives * Pregnancy within the last 3 months * Smoking \> 10 cigarettes per day **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Huntsville **Country:** United States **Facility:** Duramed Investigational Site **State:** Alabama **Zip:** 35801 **Location 2:** **City:** Mobile **Country:** United States **Facility:** Duramed Investigational Site **State:** Alabama **Zip:** 36608 **Location 3:** **City:** Phoenix **Country:** United States **Facility:** Duramed Investigational Site **State:** Arizona **Zip:** 85015 **Location 4:** **City:** Phoenix **Country:** United States **Facility:** Duramed Investigational Site **State:** Arizona **Zip:** 85031 **Location 5:** **City:** Carmichael **Country:** United States **Facility:** Duramed Investigational Site **State:** California **Zip:** 95608 **Location 6:** **City:** Irvine **Country:** United States **Facility:** Duramed Investigational Site **State:** California **Zip:** 92618 **Location 7:** **City:** San Diego **Country:** United States **Facility:** Duramed Investigational Site **State:** California **Zip:** 92108 **Location 8:** **City:** San Diego **Country:** United States **Facility:** Duramed Investigational Site **State:** California **Zip:** 92123 **Location 9:** **City:** San Ramon **Country:** United States **Facility:** Duramed Investigational Site **State:** California **Zip:** 94583 **Location 10:** **City:** Colorado Springs **Country:** United States **Facility:** Duramed Investigational Site **State:** Colorado **Zip:** 80909 **Location 11:** **City:** Lakewood **Country:** United States **Facility:** Duramed Investigational Site **State:** Colorado **Zip:** 80228 **Location 12:** **City:** Wilmington **Country:** United States **Facility:** Duramed Investigational Site **State:** Delaware **Zip:** 19805 **Location 13:** **City:** Washington **Country:** United States **Facility:** Duramed Investigational Site **State:** District of Columbia **Zip:** 20006 **Location 14:** **City:** Aventura **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33180 **Location 15:** **City:** Boynton Beach **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33437 **Location 16:** **City:** Brooksville **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33613 **Location 17:** **City:** Clearwater **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33761 **Location 18:** **City:** Coral Gables **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33134 **Location 19:** **City:** Fort Meyers **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33918 **Location 20:** **City:** Leesburg **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 34748 **Location 21:** **City:** Longwood **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 32779 **Location 22:** **City:** Miami **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33173 **Location 23:** **City:** Pinellas Park **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33781 **Location 24:** **City:** Sarasota **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 34239 **Location 25:** **City:** St. Petersburg **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33702 **Location 26:** **City:** St. Petersburg **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33709 **Location 27:** **City:** Tampa **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33613 **Location 28:** **City:** West Palm Beach **Country:** United States **Facility:** Duramed Investigational Site **State:** Florida **Zip:** 33409 **Location 29:** **City:** Atlanta **Country:** United States **Facility:** Duramed Investigational Site **State:** Georgia **Zip:** 30328 **Location 30:** **City:** Atlanta **Country:** United States **Facility:** Duramed Investigational Site **State:** Georgia **Zip:** 30342 **Location 31:** **City:** Decatur **Country:** United States **Facility:** Duramed Investigational Site **State:** Georgia **Zip:** 30034 **Location 32:** **City:** Roswell **Country:** United States **Facility:** Duramed Investigational Site **State:** Georgia **Zip:** 30075 **Location 33:** **City:** Boise **Country:** United States **Facility:** Duramed Investigational Site **State:** Idaho **Zip:** 83704 **Location 34:** **City:** Chicago **Country:** United States **Facility:** Duramed Investigational Site **State:** Illinois **Zip:** 60611 **Location 35:** **City:** Chicago **Country:** United States **Facility:** Duramed Investigational Site **State:** Illinois **Zip:** 60612 **Location 36:** **City:** Peoria **Country:** United States **Facility:** Duramed Investigational Site **State:** Illinois **Zip:** 61602 **Location 37:** **City:** Shawnee Mission **Country:** United States **Facility:** Duramed Investigational Site **State:** Kansas **Zip:** 66216 **Location 38:** **City:** Topeka **Country:** United States **Facility:** Duramed Investigational Site **State:** Kansas **Zip:** 66614 **Location 39:** **City:** Lexington **Country:** United States **Facility:** Duramed Investigational Site **State:** Kentucky **Zip:** 40509 **Location 40:** **City:** Louisville **Country:** United States **Facility:** Duramed Investigational Site **State:** Kentucky **Zip:** 40291 **Location 41:** **City:** Mt Sterling **Country:** United States **Facility:** Duramed Investigational Site **State:** Kentucky **Zip:** 40353 **Location 42:** **City:** Kansas City **Country:** United States **Facility:** Duramed Investigational Site **State:** Missouri **Zip:** 64108 **Location 43:** **City:** Lincoln **Country:** United States **Facility:** Duramed Investigational Site **State:** Nebraska **Zip:** 68510 **Location 44:** **City:** Las Vegas **Country:** United States **Facility:** Duramed Investigational Site **State:** Nevada **Zip:** 89146 **Location 45:** **City:** Moorestown **Country:** United States **Facility:** Duramed Investigational Site **State:** New Jersey **Zip:** 08057 **Location 46:** **City:** New Brunswick **Country:** United States **Facility:** Duramed Investigational Site **State:** New Jersey **Zip:** 08901 **Location 47:** **City:** Albuquerque **Country:** United States **Facility:** Duramed Investigational Site **State:** New Mexico **Zip:** 87102 **Location 48:** **City:** Johnson City **Country:** United States **Facility:** Duramed Investigational Site **State:** New York **Zip:** 13790 **Location 49:** **City:** Rochester **Country:** United States **Facility:** Duramed Investigational Site **State:** New York **Zip:** 14609 **Location 50:** **City:** Charlotte **Country:** United States **Facility:** Duramed Investigational Site **State:** North Carolina **Zip:** 28211 **Location 51:** **City:** Raleigh **Country:** United States **Facility:** Duramed Investigational Site **State:** North Carolina **Zip:** 27612 **Location 52:** **City:** Wilmington **Country:** United States **Facility:** Duramed Investigational Site **State:** North Carolina **Zip:** 28412 **Location 53:** **City:** Winston-Salem **Country:** United States **Facility:** Duramed Investigational Site **State:** North Carolina **Zip:** 27103 **Location 54:** **City:** Columbus **Country:** United States **Facility:** Duramed Investigational Site **State:** Ohio **Zip:** 43210 **Location 55:** **City:** Columbus **Country:** United States **Facility:** Duramed Investigational Site **State:** Ohio **Zip:** 43213 **Location 56:** **City:** Oklahoma City **Country:** United States **Facility:** Duramed Investigational Site **State:** Oklahoma **Zip:** 73112 **Location 57:** **City:** Medford **Country:** United States **Facility:** Duramed Investigational Site **State:** Oregon **Zip:** 97504 **Location 58:** **City:** Philadelphia **Country:** United States **Facility:** Duramed Investigational Site **State:** Pennsylvania **Zip:** 19114 **Location 59:** **City:** Reading **Country:** United States **Facility:** Duramed Investigational Site **State:** Pennsylvania **Zip:** 19606 **Location 60:** **City:** Cranston **Country:** United States **Facility:** Duramed Investigational Site **State:** Rhode Island **Zip:** 02920 **Location 61:** **City:** Greer **Country:** United States **Facility:** Duramed Investigational Site **State:** South Carolina **Zip:** 29651 **Location 62:** **City:** Mt Pleasant **Country:** United States **Facility:** Duramed Investigational Site **State:** South Carolina **Zip:** 29464 **Location 63:** **City:** Bristol **Country:** United States **Facility:** Duramed Investigational Site **State:** Tennessee **Zip:** 37620 **Location 64:** **City:** Chattanooga **Country:** United States **Facility:** Duramed Investigational Site **State:** Tennessee **Zip:** 37404 **Location 65:** **City:** Clarksville **Country:** United States **Facility:** Duramed Investigational Site **State:** Tennessee **Zip:** 37043 **Location 66:** **City:** Germantown **Country:** United States **Facility:** Duramed Investigational Site **State:** Tennessee **Zip:** 38138 **Location 67:** **City:** Knoxville **Country:** United States **Facility:** Duramed Investigational Site **State:** Tennessee **Zip:** 37920 **Location 68:** **City:** Nashville **Country:** United States **Facility:** Duramed Investigational Site **State:** Tennessee **Zip:** 37203 **Location 69:** **City:** Austin **Country:** United States **Facility:** Duramed Investigational Site **State:** Texas **Zip:** 78759 **Location 70:** **City:** Dallas **Country:** United States **Facility:** Duramed Investigational Site **State:** Texas **Zip:** 75234 **Location 71:** **City:** Houston **Country:** United States **Facility:** Duramed Investigational Site **State:** Texas **Zip:** 77030 **Location 72:** **City:** San Antonio **Country:** United States **Facility:** Duramed Investigational Site **State:** Texas **Zip:** 78229 **Location 73:** **City:** Waco **Country:** United States **Facility:** Duramed Investigational Site **State:** Texas **Zip:** 76712 **Location 74:** **City:** Magna **Country:** United States **Facility:** Duramed Investigational Site **State:** Utah **Zip:** 84044 **Location 75:** **City:** Pleasant Grove **Country:** United States **Facility:** Duramed Investigational Site **State:** Utah **Zip:** 84062 **Location 76:** **City:** Salt Lake City **Country:** United States **Facility:** Duramed Investigational Site **State:** Utah **Zip:** 84124 **Location 77:** **City:** Sandy **Country:** United States **Facility:** Duramed Investigational Site **State:** Utah **Zip:** 84070 **Location 78:** **City:** Arlington **Country:** United States **Facility:** Duramed Investigational Site **State:** Virginia **Zip:** 22203 **Location 79:** **City:** Newport News **Country:** United States **Facility:** Duramed Investigational Site **State:** Virginia **Zip:** 23602 **Location 80:** **City:** Norfolk **Country:** United States **Facility:** Duramed Investigational Site **State:** Virginia **Zip:** 23507 **Location 81:** **City:** Richmond **Country:** United States **Facility:** Duramed Investigational Site **State:** Virginia **Zip:** 23233 **Location 82:** **City:** Lakewood **Country:** United States **Facility:** Duramed Investigational Site **State:** Washington **Zip:** 98499 **Location 83:** **City:** Seattle **Country:** United States **Facility:** Duramed Investigational Site **State:** Washington **Zip:** 98105 **Location 84:** **City:** Spokane **Country:** United States **Facility:** Duramed Investigational Site **State:** Washington **Zip:** 99207 **Location 85:** **City:** Tacoma **Country:** United States **Facility:** Duramed Investigational Site **State:** Washington **Zip:** 98405 #### Overall Officials **Official 1:** **Affiliation:** Duramed Research **Name:** Duramed Medical Monitor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03832179 **Acronym:** STAMP **Brief Title:** Steroid vs. Anti-vascular Endothelial Growth Factor for Diabetic Macular Edema Prior to Phacoemulsification **Official Title:** Steroid vs. Anti-vascular Endothelial Growth Factor for Diabetic Macular Edema Prior to Phacoemulsification #### Organization Study ID Info **ID:** STAMP #### Organization **Class:** OTHER **Full Name:** Bay Area Retina Associates ### Status Module #### Completion Date **Date:** 2022-10-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2022-03-02 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-01 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2018-11-15 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2019-02-06 **Type:** ACTUAL **Study First Submit Date:** 2019-02-05 **Study First Submit QC Date:** 2019-02-05 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Allergan #### Lead Sponsor **Class:** OTHER **Name:** Bay Area Retina Associates #### Responsible Party **Investigator Affiliation:** Bay Area Retina Associates **Investigator Full Name:** Caesar Luo, MD, FACS **Investigator Title:** Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary objective of this study is to compare the efficacy of antecedent intravitreal anti-vascular endothelial growth factor therapy vs. Ozurdex in reducing post-cataract surgery related macular edema in patients with pre-existing diabetic macular edema. **Detailed Description:** In patients with pre-existing diabetic macular edema, anti-vascular endothelial growth factor therapy (Bevacizumab, ranibizumab, or aflibercept) will be compared to Ozurdex therapy administered 1 week prior to phacoemulsification cataract extraction. Spectral domain optical coherence tomography and visual acuity will be acquired at 1 week, 1 month, 2 months, and 3 months following cataract surgery. ### Conditions Module **Conditions:** - Diabetic Macular Edema - Cataract ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Two parallel groups, one group receiving anti-vascular endothelial growth factor and the other group receiving Ozurdex. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 32 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intravitreal Bevacizumab, Ranibizumab, or Aflibercept **Intervention Names:** - Drug: Bevacizumab - Drug: Ranibizumab - Drug: Aflibercept **Label:** Anti-vascular endothelial growth factor **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Intravitreal Ozurdex **Intervention Names:** - Drug: Ozurdex **Label:** Ozurdex **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Anti-vascular endothelial growth factor **Description:** Bevacizumab **Name:** Bevacizumab **Other Names:** - Avastin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Anti-vascular endothelial growth factor **Description:** Ranibizumab **Name:** Ranibizumab **Other Names:** - Lucentis **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Anti-vascular endothelial growth factor **Description:** Aflibercept **Name:** Aflibercept **Other Names:** - Eylea **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Ozurdex **Description:** Ozurdex **Name:** Ozurdex **Other Names:** - Dexamethasone implant **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Central foveal thickness will be measured in microns by spectral domain optical coherence tomography (Heidelberg) and compared to baseline at post-operative week 1, postoperative month 1, postoperative month 2, and postoperative month 3 for both anti-vascular endothelial growth factor and Ozurdex groups **Measure:** Comparison of central foveal thickness outcomes of anti-vascular endothelial growth factor vs. Ozurdex therapy **Time Frame:** 3 months after cataract surgery #### Secondary Outcomes **Description:** Snellen visual acuity will be measured and converted into logMAR and compared to baseline at post-operative week 1, postoperative month 1, postoperative month 2, and postoperative month 3 for both anti-vascular endothelial growth factor and Ozurdex groups **Measure:** Visual acuity outcomes of anti-vascular endothelial growth factor vs. Ozurdex therapy **Time Frame:** 3 months after cataract surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \> 18 years of age * Gender- All * Race- All * Diagnosis of Diabetes (Type 1 or 2) with a concomitant diagnosis of diabetic macular edema as demonstrated on spectral domain optical coherence tomography (Heidelberg Spectralis) * \>250 microns central foveal thickness * Able and willing to provide informed consent Exclusion Criteria: * Significant renal disease * A condition that in the opinion of the investigator would preclude participation * Participation in another investigational trial within 30 days of randomization * Application of focal macular laser within 120 days of enrollment * Administration of Iluvien implant within 3 years of enrollment * Administration of intravitreal triamcinolone within 3 months of enrollment * Administration of any anti-vascular endothelial growth factor agent within 30 days of enrollment * Known hypersensitivity to any of the investigational products * Blood pressure \>180/110 * Women who are pregnant, lactating, or intend to become pregnant within 1 year of randomization * Vulnerable populations- including but not limited to wards of the state, cognitively impaired individuals, prisoners, institutionalized individuals * Individual is planning on moving within 6 months of study enrollment * Macular edema secondary to cause other than diabetic macular edema * Ocular condition that, in the opinion of the investigators, may affect course of macular edema during course of study (vein occlusion, uveitis, etc.) * Evidence of ocular infections * Evidence of uncontrolled glaucoma * Known hypersensitivity to any components of bevacizumab, ranibizumab, aflibercept, or Ozurdex **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** cluo@bayarearetina.com **Name:** Caesar Luo, MD **Phone:** 9259436800 **Role:** CONTACT **Contact 2:** **Email:** fahmed@bayarearetina.com **Name:** Farhan Ahmed **Phone:** 9259436800 **Role:** CONTACT #### Locations **Location 1:** **City:** Walnut Creek **Contacts:** ***Contact 1:*** - **Email:** fahmed@bayarearetina.com - **Name:** Farhan Ahmed - **Phone:** 925-943-6800 - **Role:** CONTACT ***Contact 2:*** - **Email:** cluo@bayarearetina.com - **Name:** Caesar Luo, MD - **Phone:** 9259436800 - **Role:** CONTACT ***Contact 3:*** - **Name:** Roger Goldberg, MD, MBA - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Tushar Ranchod, MD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Subhransu Ray, MD, PhD - **Role:** SUB_INVESTIGATOR ***Contact 6:*** - **Name:** Daniel Ting, MD, PhD - **Role:** SUB_INVESTIGATOR ***Contact 7:*** - **Name:** Stewart Daniels, MD - **Role:** SUB_INVESTIGATOR ***Contact 8:*** - **Name:** Craig Leong, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Bay Area Retina Associates **State:** California **Status:** RECRUITING **Zip:** 94598 #### Overall Officials **Official 1:** **Affiliation:** Physician **Name:** Caesar Luo, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Rauen PI, Ribeiro JA, Almeida FP, Scott IU, Messias A, Jorge R. Intravitreal injection of ranibizumab during cataract surgery in patients with diabetic macular edema. Retina. 2012 Oct;32(9):1799-803. doi: 10.1097/IAE.0b013e31824bebb8. **PMID:** 22495327 **Citation:** Furino C, Boscia F, Niro A, Giancipoli E, Grassi MO, D'amico Ricci G, Blasetti F, Reibaldi M, Alessio G. Combined Phacoemulsification and Intravitreal Dexamethasone Implant (Ozurdex(R)) in Diabetic Patients with Coexisting Cataract and Diabetic Macular Edema. J Ophthalmol. 2017;2017:4896036. doi: 10.1155/2017/4896036. Epub 2017 Aug 13. **PMID:** 28884024 **Citation:** Calvo P, Ferreras A, Al Adel F, Dangboon W, Brent MH. EFFECT OF AN INTRAVITREAL DEXAMETHASONE IMPLANT ON DIABETIC MACULAR EDEMA AFTER CATARACT SURGERY. Retina. 2018 Mar;38(3):490-496. doi: 10.1097/IAE.0000000000001552. **PMID:** 28196056 **Citation:** Yumusak E, Ornek K. Comparison of Perioperative Ranibizumab Injections for Diabetic Macular Edema in Patients Undergoing Cataract Surgery. J Ophthalmol. 2016;2016:7945619. doi: 10.1155/2016/7945619. Epub 2016 Jul 14. **PMID:** 27493795 **Citation:** Lim LL, Morrison JL, Constantinou M, Rogers S, Sandhu SS, Wickremasinghe SS, Kawasaki R, Al-Qureshi S. Diabetic Macular Edema at the time of Cataract Surgery trial: a prospective, randomized clinical trial of intravitreous bevacizumab versus triamcinolone in patients with diabetic macular oedema at the time of cataract surgery - preliminary 6 month results. Clin Exp Ophthalmol. 2016 May;44(4):233-42. doi: 10.1111/ceo.12720. Epub 2016 Mar 29. **PMID:** 26871700 **Citation:** Schmier JK, Halpern MT, Covert DW, Matthews GP. Evaluation of costs for cystoid macular edema among patients after cataract surgery. Retina. 2007 Jun;27(5):621-8. doi: 10.1097/01.iae.0000249577.92800.c0. **PMID:** 17558326 **Citation:** Hayashi K, Igarashi C, Hirata A, Hayashi H. Changes in diabetic macular oedema after phacoemulsification surgery. Eye (Lond). 2009 Feb;23(2):389-96. doi: 10.1038/sj.eye.6703022. Epub 2007 Oct 26. **PMID:** 17962820 **Citation:** Hartnett ME, Tinkham N, Paynter L, Geisen P, Rosenberg P, Koch G, Cohen KL. Aqueous vascular endothelial growth factor as a predictor of macular thickening following cataract surgery in patients with diabetes mellitus. Am J Ophthalmol. 2009 Dec;148(6):895-901.e1. doi: 10.1016/j.ajo.2009.07.014. Epub 2009 Oct 17. **PMID:** 19837384 **Citation:** Ferguson VM, Spalton DJ. Continued breakdown of the blood aqueous barrier following cataract surgery. Br J Ophthalmol. 1992 Aug;76(8):453-6. doi: 10.1136/bjo.76.8.453. **PMID:** 1390524 **Citation:** Dong N, Xu B, Wang B, Chu L, Tang X. Aqueous cytokines as predictors of macular edema in patients with diabetes following uncomplicated phacoemulsification cataract surgery. Biomed Res Int. 2015;2015:126984. doi: 10.1155/2015/126984. Epub 2015 Feb 25. **PMID:** 25811020 **Citation:** Patel JI, Hykin PG, Cree IA. Diabetic cataract removal: postoperative progression of maculopathy--growth factor and clinical analysis. Br J Ophthalmol. 2006 Jun;90(6):697-701. doi: 10.1136/bjo.2005.087403. Epub 2006 Mar 15. **PMID:** 16540489 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases - ID: D000008268 - Term: Macular Degeneration - ID: D000012162 - Term: Retinal Degeneration - ID: D000012164 - Term: Retinal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M11261 - Name: Macular Edema - Relevance: HIGH - As Found: Macular Edema - ID: M7657 - Name: Edema - Relevance: HIGH - As Found: Edema - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M11260 - Name: Macular Degeneration - Relevance: LOW - As Found: Unknown - ID: M14997 - Name: Retinal Degeneration - Relevance: LOW - As Found: Unknown - ID: M14999 - Name: Retinal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract - ID: D000008269 - Term: Macular Edema - ID: D000004487 - Term: Edema ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000006131 - Term: Growth Inhibitors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000000932 - Term: Antiemetics - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000018931 - Term: Antineoplastic Agents, Hormonal ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M7102 - Name: Dexamethasone - Relevance: HIGH - As Found: Children - ID: M257727 - Name: Aflibercept - Relevance: HIGH - As Found: Magnetic Resonance Imaging - ID: M246 - Name: Bevacizumab - Relevance: HIGH - As Found: Non- - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M199152 - Name: BB 1101 - Relevance: LOW - As Found: Unknown - ID: M18681 - Name: Endothelial Growth Factors - Relevance: LOW - As Found: Unknown - ID: M11900 - Name: Mitogens - Relevance: LOW - As Found: Unknown - ID: M472 - Name: Ranibizumab - Relevance: HIGH - As Found: Dysfunction - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4251 - Name: Antiemetics - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003907 - Term: Dexamethasone - ID: D000068258 - Term: Bevacizumab - ID: D000069579 - Term: Ranibizumab - ID: C000533178 - Term: Aflibercept ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03004079 **Brief Title:** Clinical Importance of Glucose Regulation in Relapsing MS **Official Title:** Assessment of the Clinical Importance of Insulin Resistance & Steroid-Associated Hyperglycemia in Relapsing Multiple Sclerosis #### Organization Study ID Info **ID:** 19259 #### Organization **Class:** OTHER **Full Name:** University of Virginia ### Status Module #### Completion Date **Date:** 2020-09 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2018-11-07 **Type:** ACTUAL **Last Update Submit Date:** 2018-11-05 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-09 **Type:** ESTIMATED #### Start Date **Date:** 2016-10 **Status Verified Date:** 2018-11 #### Study First Post Date **Date:** 2016-12-28 **Type:** ESTIMATED **Study First Submit Date:** 2016-11-02 **Study First Submit QC Date:** 2016-12-21 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** National Multiple Sclerosis Society #### Lead Sponsor **Class:** OTHER **Name:** University of Virginia #### Responsible Party **Investigator Affiliation:** University of Virginia **Investigator Full Name:** Myla Goldman, MD **Investigator Title:** Associate Professor of the Department of Neurology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to assess the relationship of blood glucose levels in persons with Multiple Sclerosis (MS) who have experienced a relapse and will be receiving intravenous steroids for the relapse, to their recovery from the relapse. Steroid exposure commonly leads to elevated serum blood glucose, however, standardized monitoring of blood glucose levels in the outpatient setting is not common. The clinical impact of any associated elevated blood glucose during steroid administration is unknown. We hypothesize that the blood glucose response to steroid treatment is clinically relevant to the MS-relapse recovery. **Detailed Description:** Multiple Sclerosis (MS) is a neuroinflammatory and degenerative central nervous system disorder. The majority of patients have an early relapsing-remitting course. Standard treatment for an MS-relapse is intravenous methylprednisolone (IVMP), typically 1000 mg daily for 3 days. Despite IVMP treatment, \>40% of MS patients experience residual deficits after an MS-relapse. Potential risk factors for poor relapse recovery remain unclear. Elevated serum blood glucose is a common and well-defined consequence of steroid administration, attributed to steroid-related reductions in insulin sensitivity. Individuals with pre-treatment insulin resistance (e.g. diabetics) will exhibit an amplified hyperglycemic response. Reduced mobility, sedentary lifestyle, and repeated exposure to steroids- all of which are common in MS - are recognized risk factors for insulin resistance. These factors may make MS patients particularly susceptible to steroid-induced hyperglycemia. While, MS patients commonly receive intravenous steroids, the clinical impact of any associated hyperglycemia is unknown. Study Design and Methods Timeline: Study will require 3 visits over a 6 month period. Subjects: MS subjects who are experiencing an acute relapse will be recruited for the study. Prior to any study procedures, the PI or research coordinator will obtain full written informed consent. Baseline Measurements: age, race/ethnicity, sex, weight, height, waist circumference, blood pressure, previous steroid exposure (dates, frequency, steroid type and dose), smoking history, and family history of diabetes. Medication review will include MS disease-modifying therapy, symptomatic medications, and non-MS-related medications. Additional MS-related information will include dates of initial MS-symptom onset, MS diagnosis, and onset of presenting relapse symptoms. Oral glucose tolerance test (OGTT) \& Matsuda Index: Prior to steroid administration, MS subjects will undergo a 2-hour OGTT. OGTT and Matsuda Index will then be repeated at the 3- and 6-month follow-up visits. Blood studies: HgA1c (hemoglobin A1C), a fasting lipid panel (LDL-C, HDL-C, triglycerides, and total cholesterol), insulin growth factor, vitamin D level, adiponectin level, homocysteine level, and leptin level. All laboratory tests completed at baseline, 3- and 6-month visits. Surveys: Subjects will complete surveys related to their perceived disability, relapse severity and recovery, and other MS-related symptoms. Functional testing: EDSS, MS Functional Composite, timed-walk testing, accelerometry, low contrast visual acuity test (LCVA) and the symbol digit modality test (SDMT). Intravenous steroid treatment: Standardized 1000 mg of intravenous methylprednisolone (IVMP) daily for 3 days (reconstituted in 0.9% sodium chloride). IVMP will be billed to patient insurance as part of routine clinical care. Blood glucose monitoring: Bayer Contour Next glucometer will be used to measure capillary BG levels 6 times daily (Subjects will be instructed to check their BG starting on the day of screening and to continue BG checks (as above) until their return appointment 5-7 days after steroid treatment completion for a total of 8-10 days. Subjects will be required to avoid snacks between meals for the 3 days of IVMP treatment. ### Conditions Module **Conditions:** - Relapsing Remitting Multiple Sclerosis - Clinically Isolated Syndrome ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 160 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Determine the relationship between mean postprandial blood glucoses (BG) and relapse recovery (complete vs. incomplete) following a standardized IVMP treatment. **Measure:** Relapse Recovery & Hyperglycemia **Time Frame:** Recovery from relapse at 6-months **Description:** Determine if insulin resistance (IR), measured by the Matsuda Index, is an independent predictor of relapse severity. **Measure:** Insulin Resistance & Relapse Severity **Time Frame:** At Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ability to provide informed consent * Age 18 -59 years (inclusive) * Ability to walk continuously for 6 minutes (per patient report) * Clinically Isolated Syndrome (CIS) or Relapsing Remitting MS (RRMS) confirmed diagnosis by McDonald 2010 criteria * Current MS relapse with objective findings on exam * Relapse symptom onset within 2-weeks of screening * Functional System Scores obtainable from a clinic visit within 6 months of the relapse assessment visit * EDSS \< 6.5 at time of screening visit * Inpatient, outpatient, emergency department, or inpatient observation status Exclusion Criteria: * Prior steroid exposure within 90 days of enrollment * HgA1c ≥ 6.5 at baseline screening * Evidence of concurrent infection * Known contraindications to IV steroid treatment * History of diabetes mellitus ( type 1 or 2) or severe hypertension * Use of any glucose-regulating medications * Pregnancy or current use of hormone replacement therapy **Maximum Age:** 59 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** Adults aged 18-54 (inclusive) with a diagnosis of clinically isolated syndrome or relapsing remitting multiple sclerosis with an acute attack (relapse). ### Contacts Locations Module #### Central Contacts **Contact 1:** **Name:** Myla Goldman, MD **Phone:** 434-243-6069 **Role:** CONTACT **Contact 2:** **Email:** rcoleman@virginia.edu **Name:** Rachael Coleman, MPH **Phone:** 434-297-4102 **Role:** CONTACT #### Locations **Location 1:** **City:** Charlottesville **Contacts:** ***Contact 1:*** - **Email:** rcoleman@virginia.edu - **Name:** Rachael Coleman, MPH - **Phone:** 434-297-4102 - **Role:** CONTACT ***Contact 2:*** - **Name:** Myla Goldman, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** University of Virginia **State:** Virginia **Status:** RECRUITING **Zip:** 22903 #### Overall Officials **Official 1:** **Affiliation:** University of Virginia **Name:** Myla Goldman, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Nickerson M, Marrie RA. 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Pharmacol Ther. 2005 May;106(2):163-77. doi: 10.1016/j.pharmthera.2004.11.007. Epub 2005 Jan 11. **PMID:** 15866318 **Citation:** Schneider A, Long SA, Cerosaletti K, Ni CT, Samuels P, Kita M, Buckner JH. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T(regs) involves IL-6-mediated signaling. Sci Transl Med. 2013 Jan 30;5(170):170ra15. doi: 10.1126/scitranslmed.3004970. **PMID:** 23363979 **Citation:** Warabi Y. Role of IL-1 and potential therapies in multiple sclerosis. Drug Discovery Today: Therapeutic Strategies 2007;4:19-24. **Citation:** Juhler M. Simultaneous determination of regional cerebral blood flow, glucose metabolism, and pH in acute experimental allergic encephalomyelitis. J Cereb Blood Flow Metab. 1987 Oct;7(5):578-84. doi: 10.1038/jcbfm.1987.108. **PMID:** 3654798 **Citation:** Juhler M. Pathophysiological aspects of acute experimental allergic encephalomyelitis. Acta Neurol Scand Suppl. 1988;119:1-21. doi: 10.1111/j.1600-0404.1988.tb08016.x. **PMID:** 3064529 **Citation:** JONES HH, JONES HH Jr, BUNCH LD. Biochemical studies in multiple sclerosis. Ann Intern Med. 1950 Oct;33(4):831-40. doi: 10.7326/0003-4819-33-4-831. No abstract available. **PMID:** 14771754 **Citation:** Sternberg Z, Leung C, Sternberg D, Yu J, Hojnacki D. Disease modifying therapies modulate cardiovascular risk factors in patients with multiple sclerosis. Cardiovasc Ther. 2014 Apr;32(2):33-9. doi: 10.1111/1755-5922.12049. **PMID:** 24119301 **Citation:** Mowry EM, Pesic M, Grimes B, Deen S, Bacchetti P, Waubant E. Demyelinating events in early multiple sclerosis have inherent severity and recovery. Neurology. 2009 Feb 17;72(7):602-8. doi: 10.1212/01.wnl.0000342458.39625.91. **PMID:** 19221292 **Citation:** Penesova A, Vlcek M, Imrich R, Vernerova L, Marko A, Meskova M, Grunnerova L, Turcani P, Jezova D, Kollar B. Hyperinsulinemia in newly diagnosed patients with multiple sclerosis. Metab Brain Dis. 2015 Aug;30(4):895-901. doi: 10.1007/s11011-015-9665-1. Epub 2015 Mar 27. **PMID:** 25809135 **Citation:** SCHUMACHER GA, BEEBE G, KIBLER RF, KURLAND LT, KURTZKE JF, MCDOWELL F, NAGLER B, SIBLEY WA, TOURTELLOTTE WW, WILLMON TL. PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS. Ann N Y Acad Sci. 1965 Mar 31;122:552-68. doi: 10.1111/j.1749-6632.1965.tb20235.x. No abstract available. **PMID:** 14313512 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M10370 - Name: Insulin Resistance - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M22314 - Name: Multiple Sclerosis, Relapsing-Remitting - Relevance: HIGH - As Found: Relapsing Remitting Multiple Sclerosis - ID: M9994 - Name: Hyperglycemia - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000020529 - Term: Multiple Sclerosis, Relapsing-Remitting - ID: D000012598 - Term: Sclerosis ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03719079 **Acronym:** Nanosense **Brief Title:** Nanowear Heart Failure Management Multi-sensor Algorithm **Official Title:** The Nanowear Wearable Heart Failure Management System Multiple Sensor Algorithm Development and Validation Trial #### Organization Study ID Info **ID:** NWCT18-SS-001 #### Organization **Class:** INDUSTRY **Full Name:** Nanowear Inc. ### Status Module #### Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-08 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-07 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2019-08-21 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2018-10-25 **Type:** ACTUAL **Study First Submit Date:** 2018-10-23 **Study First Submit QC Date:** 2018-10-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Milton S. Hershey Medical Center **Class:** OTHER **Name:** Hackensack Meridian Health #### Lead Sponsor **Class:** INDUSTRY **Name:** Nanowear Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is Unapproved Device:** True **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The NanoSense study is a multi-center, prospective, non-randomized, observational, feasibility, non-significant risk study. The NanoSense study will enroll up to 500 subjects in up to 10 centers in order to collect data which includes at least 150 heart failure hospitalizations in participating subjects.The duration of the NanoSense study is expected to be 2 years. The study device is the Wearable Congestive Heart Failure Management System (WCHFS, also known as SimpleSENSE) **Detailed Description:** NanoSense is a data collection study to develop a multi-sensor algorithm to predict worsening Heart Failure (HF). Subjects who meet the eligibility criteria and agree to participate in the study will enter the informed consent process in which the subject will be informed about the research study, the voluntary nature of the research and all attendant risks and benefits. Once the subject has been informed and all question answered, the subject will be asked to sign an informed consent document (approved by the local Institutional Review Board). At enrollment, data about subject demographics, cardiac disease history, and comorbidities will be collected. The subject vital signs, blood labs (as available; if an N-terminal pro b-type natriuretic peptide (NT-proBNP) is not available, one will be ordered to coincide with the next lab samples), HF medications and HF assessment measurements will be made and recorded. Subjects will be given a diary to record daily weights, diuretics changes, and weekly HF status. The subject will be fitted with a Nanowear Wearable Congestive Heart Failure System (WCHFS) and educated on the use of the system with attention to proper fit and changing or charging the battery daily depending on the type of battery used. Subjects who have a pacemaker or Implantable Cardioverter Defibrillator (ICD) will undergo pacemaker/ICD interrogation while wearing the device to assure that there are no electrical signals detected that may interfere with pacemaker or ICD function. The subjects will be asked to wear the device for approximately 12 hours daily including 2 hours prior to sleep and 2 hours after awakening. The follow-up period will be 90 days. At visit 2, the clinical assessment will be repeated and recorded. The device will be retrieved from the subject. In the event that a subject is unable to travel to the investigator's site, the subject will be asked to mail the device back to the sponsor with use of a prepaid mailing package that will be delivered to the subject. Data may be obtained by phone if the subject is unable or unwilling to return for visit 2. A final contact will be made to the subject at 30 days following visit 2 to determine whether there were any adverse effects that were not previously recognized that may be related to their participation in the study. ### Conditions Module **Conditions:** - Heart Failure **Keywords:** - Fluid decompensation - Non-invasive Multi-parameter monitoring - Multi-parameter algorithm - Heart Rate Variability - Thoracic impedance - Heart Sounds - Respiration - Posture - Activity - Tidal Volume - Stroke Volume ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 500 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with primary diagnosis as heart failure **Intervention Names:** - Device: SimpleSENSE **Label:** Heart Failure Patients ### Interventions #### Intervention 1 **Arm Group Labels:** - Heart Failure Patients **Description:** The Nanosense study is observational only. No interventions will be triggered by the SimpleSense device **Name:** SimpleSENSE **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The primary objective of the study is to develop and validate a multi-parameter algorithm for the detection of heart failure prior to a HF event. For the purpose of this study, a heart failure event will be defined as a hospitalization with a primary diagnosis of heart failure. **Measure:** Multi-parameter algorithm **Time Frame:** 90 days per patient and till 100 Heart Failure events are observed overall. #### Secondary Outcomes **Description:** Exploratory information will be used to compare the signals obtained from the device to the severity of heart failure as measured by clinical evaluation (NYHA functional class and physical examination) and NT-proBNP **Measure:** Exploratory comparison of signals from device to NT-proBNP **Time Frame:** 90 days per patient and till 100 Heart Failure events are observed overall. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject has provided informed consent * Male or female over the age of 18 years * The patient is either hospitalized with a primary diagnosis of acute or was discharged with a primary diagnosis of acute heart failure within 2 weeks prior to enrollment * NYHA functional class II-IV at time of enrollment Exclusion Criteria: * Subject unwilling or unable to comply with wearing the Nanowear Congestive Heart Failure Management System 12 hours daily for up to 90 days. * Subjects who are limited by angina. * Severe aortic stenosis. * Subjects who are hemodynamically unstable requiring support with intravenous vasoactive medications or mechanical circulatory support * Symptomatic ventricular arrhythmias within the past 6 months. * Subjects who are pregnant will be excluded from this study. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects of legal age to give informed consent who are currently or recently hospitalized with a primary diagnosis of heart failure ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** jboehmer@pennstatehealth.psu.edu **Name:** John P Boehmer, M.D. **Phone:** 717-531-7453 **Role:** CONTACT **Contact 2:** **Email:** venk@nanowearinc.com **Name:** Venkatesh Varadan **Role:** CONTACT #### Locations **Location 1:** **City:** Hershey **Contacts:** ***Contact 1:*** - **Email:** kloffredo@pennstatehealth.psu.edu - **Name:** Katie Loffredo, RN, BSN, CCRC - **Phone:** (717) 531-6855 - **Role:** CONTACT **Country:** United States **Facility:** Penn State Health Milton S. Hershey Medical Center **State:** Pennsylvania **Status:** RECRUITING **Zip:** 17033 #### Overall Officials **Official 1:** **Affiliation:** Milton S. Hershey Medical Center **Name:** John P Boehmer, M.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M22306 - Name: Stroke - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03271879 **Acronym:** ERA-HF **Brief Title:** Empagliflozin Versus Placebo on the Rate of Arrhythmic Events in Heart Failure Patients **Official Title:** The Effect of Empagliflozin Versus Placebo on the Rate of Arrhythmic Events in Heart Failure Patients #### Organization Study ID Info **ID:** 605-16 #### Organization **Class:** OTHER **Full Name:** Rambam Health Care Campus ### Status Module #### Completion Date **Date:** 2020-06-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2018-01-25 **Type:** ACTUAL **Last Update Submit Date:** 2018-01-24 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2018-02-15 **Type:** ESTIMATED **Status Verified Date:** 2018-01 #### Study First Post Date **Date:** 2017-09-05 **Type:** ACTUAL **Study First Submit Date:** 2017-07-30 **Study First Submit QC Date:** 2017-08-31 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Boehringer Ingelheim #### Lead Sponsor **Class:** OTHER **Name:** Rambam Health Care Campus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Empagliflozin treatment in high cardiovascular risk patients has been shown to have a relatively rapid powerful capability in reducing cardiovascular mortality. Among the suggested mechanisms mediating this effect of empagliflozin, anti-arrhythmic effect (AAE) has the highest potential to translate into a rapid clinical beneficial effect on cardiovascular mortality, while other mechanisms are known to have a lag in their clinical effect based on data from previous studies. Based on this assumption, the study driving hypothesis is that the effect of empagliflozin on the rate of cardiovascular death may be mediated by a direct effect on the risk for arrhythmic events (via a direct or an indirect effect on the myocardium). The current study aims at assessing the effect of empagliflozin on arrhythmias in diabetic patients with HF with reduced ejection fraction and relatively high arrhythmic burden. The objective of the current study is to demonstrate the effect of empagliflozin compared to placebo on the rate of ventricular arrhythmic events in type 2 diabetes patients with heart failure with reduced ejection fraction and high risk arrhythmic profile. **Detailed Description:** Background and rationale: Empagliflozin is an orally available inhibitor of the sodium-glucose co-transporter 2 (SGLT-2), that promotes enhanced glucose excretion in the urine, thereby lowering blood glucose concentrations in patients with type 2 diabetes mellitus (T2DM). The EMPA-REG OUTCOME study demonstrated a significant reduction in both heart failure hospitalization and cardiovascular death in type 2 diabetes patients with high risk for cardiovascular events. A potential mechanism underlying the pleiotropic and explaining the remarkable early reduction in cardiovascular mortality may be related to the effect of empagliflozin on arrhythmic events. Multiple potential mechanisms have been suggested to mediate the positive cardiovascular effect of empagliflozin (altered cardiomyocyte metabolism, anti-arrhythmic effect, improved glycemic control, positive effect on myocardial contractility). Ventricular arrhythmias and the associated sudden cardiac death (SCD) is the leading cause of mortality in patients with heart failure. The risk for the occurrence of SCD in heart failure patients is closely related to the etiology (ischemic versus non-ischemic) and the left ventricular EF. The introduction of defibrillation therapy for primary prevention of SCD in HF patients has revolutionized the field during the last 2 decades. Nevertheless, ventricular arrhythmias remain a major cause of mortality for HF patients given the limited ability for risk stratification, and the dreadful prognosis associated with ventricular arrhythmias treated by defibrillation therapy. The burden of premature ventricular Complexes (PVCs) has been shown as an independent risk factor for ventricular tachyarrhythmia and SCD for healthy, ischemic and heart failure patients (with and without resynchronization and/or defibrillator therapy). Anti-arrhythmic drugs (AAD) are efficient in suppressing the occurrence of PVCs but for certain drugs, the associated with profile of adverse events and cardiotoxicity may paradoxically increase the rate of sudden cardiac death as learned by the remarkable CAST study. Be that as it may, easily suppressed PVC burden (without the associated adverse profile of AADs) has been suggested to correlate with reduction of the likelihood for SCD. Furthermore, the growing field of PVC ablation has been shown to have beneficial effect on cardiac function and the risk for ventricular arrhythmia. In summary, PVC suppression, a once neglected strategy, is now considered a promising strategy for evaluating the effect of therapeutic strategies on the risk for SCD. Empagliflozin treatment in high cardiovascular risk patients has been shown to have a relatively rapid powerful capability in reducing cardiovascular mortality. Among the suggested mechanisms mediating this effect of empagliflozin, anti-arrhythmic effect (AAE) has the highest potential to translate into a rapid clinical beneficial effect on cardiovascular mortality, while other mechanisms are known to have a lag in their clinical effect based on data from previous studies. Based on this assumption, the study driving hypothesis is that the effect of empagliflozin on the rate of cardiovascular death may be mediated by a direct effect on the risk for arrhythmic events (via a direct or an indirect effect on the myocardium). The current study aims at assessing the effect of empagliflozin on arrhythmias in diabetic patients with HF with reduced EF and relatively high arrhythmic burden. Study Objectives The objective of the current study is to demonstrate the effect of empagliflozin compared to placebo on the rate of ventricular arrhythmic events in type 2 diabetes patients with heart failure with reduced ejection fraction and high risk arrhythmic profile. Primary endpoint: The primary endpoint is the burden of premature ventricular complexes, defined as the PVCs percentage of all beats in a pre-specified period captured on implantable cardioverter-defibrillator ( ICD ) or CRTD/P device. Secondary endpoint: 1. The number of non-sustained ventricular tachycardia (NSVT) episodes. 2. A composite cumulative endpoint of ventricular arrhythmia load (number of: sustained ventricular tachycardia, ventricular fibrillation, antitachycardia pacing (ATP) or delivery of shock therapy episodes. 3. The change in blood level of NT-Pro Brain Natriuretic peptide (BNP) from baseline to the end of any of the treatment periods. 4. The change in Left ventricular end diastolic diameter on echocardiography from baseline to the end of any of the treatment periods. 5. The change in left ventricular ejection fraction (EF) on echocardiography from baseline to the end of any of the treatment periods. 6. Safety endpoints (as detailed bellow). Study Design: The present study is a randomized, prospective, controlled, double blind, cross-over, pairwise, add on standard therapy, event driven study, comparing empagliflozin versus placebo on the ventricular arrhythmia burden in a blocked randomization stratified by ischemic versus non-ischemic cardiomyopathy and PVC burden at screening of\< or \> to 4%. Potential study subjects will sign an informed consent prior to undergoing any study related procedure. Number of patients to be enrolled is 128. This study encompass 4 periods for each study subject: screening period of 8 weeks, first treatment period of 8 weeks, washout period of 4 weeks and a second treatment period of 8 weeks. Expected duration of subject participation is 6-7 months. Duration of study: The duration of the treatment period is approximately 6 months. This time span is required for completing the therapy and determining the safety profile of the drug combination and the response rate. Estimated accrual duration: 12 months. Estimated total trial duration: 18 months (for each center). ### Conditions Module **Conditions:** - Heart Failure - Diabetes Mellitus - Arrythmia **Keywords:** - Diabetes - Heart - Arrhythmia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Patients will receive study drug: empagliflozin or placebo for an exposure period of up to 16 weeks - at the two treatment periods in a crossover design. ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 128 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will be treated with 10mg Empagliflozin once daily for 8 weeks. Patient glucose levels will be monitored based on home monitoring during the treatment period. **Intervention Names:** - Drug: Empagliflozin at a dose of 10 mg/day **Label:** Empagliflozin at a dose of 10 mg/day **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients will be treated with Placebo once daily for 8 weeks. Patient glucose levels will be monitored based on home monitoring during the treatment period. **Intervention Names:** - Drug: Empagliflozin at a dose of 10 mg/day **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Empagliflozin at a dose of 10 mg/day - Placebo **Description:** Comparing empagliflozin versus placebo on the ventricular arrhythmia burden. This study encompass 4 periods for each study subject: screening period of 8 weeks, first treatment period of 8 weeks, washout period of 4 weeks and a second treatment period of 8 weeks in a cross-over design **Name:** Empagliflozin at a dose of 10 mg/day **Other Names:** - JARDIANCE at a dose of 10mg/day **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** PVCs burden is defined as the PVCs percentage of all beats in a pre-specified period captured on ICD or CRTD/P device. The change in PVC burden between time on treatment arm versus time on placebo will be calculated and serve as the primary endpoint. **Measure:** The primary endpoint is the burden of premature ventricular complexes, defined as the PVCs percentage of all beats in a pre-specified period captured on ICD or CRTD/P device **Time Frame:** Time frames include the time frame between visit 2 (on day 56) and visit 3 (on day 112) and that between visit 4 (on day 140) to visit 5 (on day 196)- each period between visits 2 and 3 and visit 4 and 5 contain a time frame of 56 days #### Secondary Outcomes **Description:** This is defined as the number of sustained ventricular tachycardia, and/or ventricular fibrillation, and/or tachycardia pacing (ATP) and/or delivery of shock therapy. All the four parameters will be captured on ICD or CRTD/P device interrogation. Sustained VT and NSVT will be captured as a backup information (in case of ICD or CRTD/P malfunction) on Holter ECG. **Measure:** Non-sustained ventricular tachycardia (NSVT) **Time Frame:** Time frames include the time frame between visit 2 (on day 56) and visit 3 (on day 112) and that between visit 4 (on day 140) to visit 5 (on day 196)- each period between visits 2 and 3 and visit 4 and 5 contain a time frame of 56 days **Description:** NT-Pro-BNP Is a plasma level of B-type Natriuretic Peptide used as a blood test for diagnosing and evaluation the presence/severity of heart failure. The change in NT-Pro-BNP will be evaluated as a marker of heart failure severity. **Measure:** NT-Pro-BNP **Time Frame:** Time frames include NT-Pro-BNP measurement on the end of visit 3 (on day 112) versus NT-Pro-BNP level at the end of visit 5 (on day 196). **Description:** End diastolic diameter is defined as the cross-sectional diameter of the left ventricle, including the septum and the posterior thicknesses in diastole. **Measure:** Left ventricular end diastolic diameter **Time Frame:** Time frames include left ventricular diastolic diameter measured on the end of visit 3 (on day 112) versus that measured at the end of visit 5 (on day 196). **Description:** Ejection fraction is defined as the ratio of the stroke volume to the end-diastolic volume in the left ventricle as performed by echocardiography and expressed by percentage. **Measure:** Left ventricular ejection fraction (EF) **Time Frame:** Time frames include EF measured on visit 3 (on day 112) versus that measured at the end of visit 5 (on day 196). ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Heart failure patients with reduced ejection fraction (EF≤40%) as assessed by echocardiographist least 6 months prior to recruitment and NYHA Class≥2 2. Patients implanted with ICD, CRTD/S or CRTP devices that are capable of recording the PVC burden and implanted ≥ 2 months prior to recruitment. 3. High risk for arrhythmic events at baseline identified by either PVC burden ≥0.5% or ≥2 events of non sustained VT or ≥1 event of sustained ventricular tachycardia or need for anti-tachycardia pacing or defibrillation therapy, during a period of 2 months prior to recruitment. 4. Diagnosis of type 2 diabetes mellitus prior to informed consent 5. HbA1c≥7% and ≤12%. 6. Signed and dated written informed consent by date of Visit 1 in accordance with GCP legislation - Exclusion Criteria: 1. Evidence of ICD malfunction. 2. Past exposure to SGLT2 inhibitors. 3. Uncontrolled diabetes with HbA1c\>12% or glucose \>240 mg/dL after an overnight fast. 4. Liver abnormalities defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal. 5. Planned cardiac procedure within 3 months. 6. Prior MI in the last 40 days. 7. Calculated eGFR\< 45ml/min/1.73m2 as determined by the MDRD formula GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) 8. BMI\>50 9. Medical History of active cancer in the last 2 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b). 10. History of recurrent UTIs or genital infections 11. Systolic blood pressure\< 90 mmHg. 12. Alcohol or drug abuse within 3 months of informed consent. 13. Pre-menopausal women (last menstruation \<+ 1 year prior to informed consent) who: * - are nursing or pregnant or * - are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method and vasectomised partner. 14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial involving an investigational drug and/or follow-up - **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** orencaspi@gmail.com **Name:** Oren Caspi, MD **Phone:** 97247772180 **Role:** CONTACT **Contact 2:** **Email:** s_rispler@rambam.health.gov.il **Name:** Shmuel Rispler, MD **Phone:** 97247772180 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Rambam MC **Name:** Oren Caspi, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** IPD will be shared following approval of the submitted research proposal by the researcher applying. **IPD Sharing:** UNDECIDED ## Document Section ### Large Document Module #### Large Docs - Date: 2017-05-14 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 2597307 - Type Abbrev: Prot_SAP - Upload Date: 2017-07-20T07:32 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: HIGH - As Found: Arrhythmia - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure - ID: D000001145 - Term: Arrhythmias, Cardiac ### Intervention Browse Module - Ancestors - ID: D000077203 - Term: Sodium-Glucose Transporter 2 Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M258082 - Name: Empagliflozin - Relevance: HIGH - As Found: At home - ID: M1691 - Name: Sodium-Glucose Transporter 2 Inhibitors - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000570240 - Term: Empagliflozin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00085579 **Brief Title:** Interleukin-2 and Sargramostim After Chemotherapy in Treating Patients With Stage III or Stage IV Melanoma **Official Title:** A Phase II Study of Maintenance Biotherapy With Interleukin-2 and Granulocyte-Macrophage Colony Stimulating Factor in Patients With Metastatic Melanoma With a Partial Response or Stable Disease After Systemic Therapy #### Organization Study ID Info **ID:** 04-027 #### Organization **Class:** OTHER **Full Name:** Memorial Sloan Kettering Cancer Center #### Secondary ID Infos **ID:** MSKCC-04027 ### Status Module #### Completion Date **Date:** 2005-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-12-12 **Type:** ESTIMATED **Last Update Submit Date:** 2012-12-11 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2005-03 **Type:** ACTUAL #### Start Date **Date:** 2004-03 **Status Verified Date:** 2012-12 #### Study First Post Date **Date:** 2004-06-11 **Type:** ESTIMATED **Study First Submit Date:** 2004-06-10 **Study First Submit QC Date:** 2004-06-10 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** Memorial Sloan Kettering Cancer Center ### Description Module **Brief Summary:** RATIONALE: Interleukin-2 and sargramostim may stimulate a person's white blood cells to kill melanoma cells. PURPOSE: This phase II trial is studying how well giving interleukin-2 together with sargramostim works in treating patients with stage III or stage IV melanoma that was previously treated with chemotherapy. **Detailed Description:** OBJECTIVES: Primary * Determine the frequency of complete response in patients with stage III or IV melanoma who have achieved either a partial response or stable disease after prior systemic chemotherapy and are treated with maintenance biotherapy comprising interleukin-2 and sargramostim (GM-CSF). Secondary * Determine the time to progression in patients treated with this regimen. * Determine the effects of this regimen on lymphocyte subsets in these patients. OUTLINE: Patients are stratified according to response to prior systemic chemotherapy (stable disease \[SD\] vs partial response \[PR\]). Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14 and low-dose interleukin-2 (IL-2) SC on days 1-5, 8-12, 15-19, and 22-26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive pulses of high-dose IL-2\* IV continuously over 42 hours on days 1 and 2 of courses 2, 3, 5, 6, 8, 10 and 12. NOTE: \*Low-dose IL-2 and GM-CSF are not administered on days 1 and 2 of high-dose IL-2 administration Patients who continue to have SD or a PR after 12 courses of therapy may continue to receive treatment with GM-CSF and low-dose IL-2 as described above and high-dose IL-2 on days 1 and 2 of every third course. PROJECTED ACCRUAL: A total of 20-58 patients (10-29 per stratum) will be accrued for this study. ### Conditions Module **Conditions:** - Melanoma (Skin) **Keywords:** - stage III melanoma - stage IV melanoma ### Design Module #### Design Info ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** aldesleukin **Type:** BIOLOGICAL #### Intervention 2 **Name:** sargramostim **Type:** BIOLOGICAL #### Intervention 3 **Name:** adjuvant therapy **Type:** PROCEDURE ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: * Histologically confirmed melanoma * Stage III or IV disease * No primary ocular melanoma * Stable disease (SD) or partial response (PR) after prior systemic chemotherapy completed at least 4 weeks ago * Patients whose second post-chemotherapy evaluation (performed at least 4 weeks after the first evaluation that demonstrated SD or PR AND within 2 weeks before study entry) of disease demonstrates continued tumor shrinkage are not eligible * Patients whose second evaluation shows disease progression are eligible unless one of the following is true: * Lactic dehydrogenase (LDH) ≥ 2 times upper limit of normal (ULN) * LDH \> ULN AND is higher than the patient's highest value before systemic chemotherapy * Patient has developed a new tumor measuring \> 1 cm in diameter * Sum of the longest diameters of the existing tumor has increased \> 20% * Evaluable or measurable disease * Not potentially curable by surgery * No active CNS metastases * Solitary brain metastasis allowed if completely resected or completely ablated with radiosurgery more than 1 month before study entry PATIENT CHARACTERISTICS: Age * 16 and over Performance status * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * WBC ≥ 3,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * No active bleeding Hepatic * See Disease Characteristics * Bilirubin ≤ 2.0 mg/dL Renal * Creatinine ≤ 1.2 mg/dL Cardiovascular * Patients ≥ 50 years of age OR those with one or more cardiac risk factors must demonstrate one of the following: * Normal exercise stress test * Normal stress thallium test * Normal comparable cardiac ischemia evaluation * LVEF ≥ 40% Other * No active infection requiring treatment * No concurrent medical or psychiatric condition that would increase the potential toxicity of study treatment * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception PRIOR CONCURRENT THERAPY: Biologic therapy * No other concurrent antineoplastic biologic response modifier therapy * No concurrent antineoplastic vaccine therapy Chemotherapy * See Disease Characteristics * No concurrent antineoplastic chemotherapy Endocrine therapy * No concurrent steroidal antiemetics * No concurrent systemic corticosteroids Radiotherapy * See Disease Characteristics * No concurrent antineoplastic radiotherapy Surgery * See Disease Characteristics * Recovered from prior surgery * Surgery within the past 4 weeks allowed provided there is no evidence of disease progression Other * More than 4 weeks since prior therapy for melanoma * No other concurrent antineoplastic experimental therapy **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New York **Country:** United States **Facility:** Memorial Sloan-Kettering Cancer Center **State:** New York **Zip:** 10021 #### Overall Officials **Official 1:** **Affiliation:** Memorial Sloan Kettering Cancer Center **Name:** Paul B. Chapman, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Memorial Sloan Kettering Cancer Center **Name:** Jedd D. Wolchok, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000018358 - Term: Neuroendocrine Tumors - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009380 - Term: Neoplasms, Nerve Tissue - ID: D000018326 - Term: Nevi and Melanomas - ID: D000012878 - Term: Skin Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11528 - Name: Melanoma - Relevance: HIGH - As Found: Melanoma - ID: M20495 - Name: Neuroendocrine Tumors - Relevance: LOW - As Found: Unknown - ID: M19845 - Name: Neuroectodermal Tumors - Relevance: LOW - As Found: Unknown - ID: M20388 - Name: Neuroectodermal Tumors, Primitive - Relevance: LOW - As Found: Unknown - ID: M12318 - Name: Neoplasms, Germ Cell and Embryonal - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: M12448 - Name: Nevus, Pigmented - Relevance: LOW - As Found: Unknown - ID: M12446 - Name: Nevus - Relevance: LOW - As Found: Unknown - ID: M20470 - Name: Nevi and Melanomas - Relevance: LOW - As Found: Unknown - ID: M15681 - Name: Skin Neoplasms - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: LOW - As Found: Unknown - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008545 - Term: Melanoma ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000970 - Term: Antineoplastic Agents - ID: D000019380 - Term: Anti-HIV Agents - ID: D000044966 - Term: Anti-Retroviral Agents - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M225496 - Name: Aldesleukin - Relevance: HIGH - As Found: Platinum - ID: M257633 - Name: Molgramostim - Relevance: LOW - As Found: Unknown - ID: M219218 - Name: Sargramostim - Relevance: HIGH - As Found: Irradiation - ID: M10411 - Name: Interleukin-2 - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M21350 - Name: Anti-HIV Agents - Relevance: LOW - As Found: Unknown - ID: M25428 - Name: Anti-Retroviral Agents - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000082598 - Term: Aldesleukin - ID: C000081222 - Term: Sargramostim ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02058979 **Brief Title:** Pharmacokinetics of Bolus Versus Continuous Cefazolin Infusion in Patients Undergoing Major Surgery **Official Title:** Pharmacokinetics of Bolus Versus Continuous Cefazolin Infusion in Patients Undergoing Major Surgery #### Organization Study ID Info **ID:** 17266 #### Organization **Class:** OTHER **Full Name:** University of Virginia ### Status Module #### Completion Date **Date:** 2016-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-10-26 **Type:** ESTIMATED **Last Update Submit Date:** 2016-10-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-06 **Type:** ACTUAL #### Start Date **Date:** 2014-11 **Status Verified Date:** 2016-10 #### Study First Post Date **Date:** 2014-02-11 **Type:** ESTIMATED **Study First Submit Date:** 2014-02-06 **Study First Submit QC Date:** 2014-02-10 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** The University of Queensland #### Lead Sponsor **Class:** OTHER **Name:** University of Virginia #### Responsible Party **Investigator Affiliation:** University of Virginia **Investigator Full Name:** Bhiken I. Naik, MD **Investigator Title:** Assistant Professor, Anesthesiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Abstract The administration of an antibiotic preoperatively is an important intervention that helps to reduce the risk of post-operative health-care associated infections (HCAI). These include urinary tract, surgical site and blood stream infection. Based on the current Surgical Infection Prevention Project, (SCIP) recommendations, the choice of the antibiotic is based on the nature and site of the surgery and the presence of a β-lactam allergy (Table 1). Currently, the antibiotic treatment for preventing surgical infections is administered as a single bolus an hour before surgery, and every four hours after the initial dose. This presents a concentration profile that has a high concentration after the bolus, but decays as the kidneys remove the antibiotics. In this present study, investigators would like to compare this traditional method of delivery to a constant infusion model that would sustain a constant level of antibiotics that is defined by the difference between the rate of infusion and rate of clearance. **Detailed Description:** The current incidence of post-operative surgical infections varies between 6% for patients undergoing non-cardiac surgery to greater than 30% in high-risk surgery. 1 The administration of an antibiotic preoperatively is an important intervention that helps to reduce the risk of post-operative health-care associated infections (HCAI). These include urinary tract, surgical site and blood stream infection. Based on the current Surgical Infection Prevention Project, (SCIP) recommendations, the choice of the antibiotic is based on the nature and site of the surgery and the presence of a β-lactam allergy (Table 2). The antibiotic of choice for perioperative prophylaxis remains first and second generation cephalosporin. These drugs have a broad range of antimicrobial activity against common skin pathogens and have an excellent safety profile. Based on current recommendations, the cephalosporin is administered 1 hour prior to incision.1 Timing is critical, as both early and late administration of the antibiotic is associated with an increase risk of HCAI. Additional doses of the cephalosporin are administered at pre-set intervals based on the duration of the surgery in an attempt to maintain antibiotic concentrations at a desired level. Antibiotics can be classified into two broad classes, based on their bacterial killing characteristics. Antibiotics with concentration-dependent killing characteristics require a high ratio between the peak concentration and the minimum inhibitory concentration (MIC) of the pathogen, during the dosing interval. Therefore large infrequent doses of these antibiotics will result in optimal antibacterial activity. In contrast β-lactam antibiotics, like cephalosporins, demonstrate time-dependent pharmacokinetics. This means that effective microbiological activity only occurs if the unbound (or free) plasma concentration of the drug is above the MIC for a specified time period. In infection models, bacteriostatic and bacteriocidical activity occurs when antibiotic concentrations are maintained above the MIC for 35-40% and 60-70% of the dosing interval respectively. However, in surgical prophylaxis, it is preferred that antibiotic concentrations are maintained above the MIC of the likely pathogen/s for the entire duration of the procedure. Therefore more frequent dosing or use of extended or continuous infusion of these drugs will better maintain the pharmacokinetic goals. Recent studies have shown that plasma levels of β-lactam antibiotics fall below the MIC 1-2 hours after the initial bolus dose in both normal and obese patients.2, 3 Even with appropriate re-dosing of the β-lactam antibiotic, there are times when the plasma concentration of the drug is below the MIC. The combination of sub-MIC plasma drug level and high bacteremic load can potentially increase the risk of developing a post-operative HCAI. It follows that to effectively prevent microbiological activity in the perioperative period the β-lactam antibiotic must remain above the MIC during the entire operative period. This is of particular importance in patients undergoing major abdominal surgery where the risk of perioperative surgical site infection (including superficial, deep and organ specific infection) is 13.1%. The aim of this study is to compare the pharmacokinetics of bolus and continuous cefazolin infusion during major abdominal surgery. Hypothesis to be Tested Hypothesis A continuous infusion of cefazolin maintains the unbound plasma concentration above Minimum Inhibitory Concentration (MIC) for the duration of the operative procedure better than the traditional bolus administration at every four hours. Specific Aims 1. Compare the pharmacokinetics of a bolus versus continuous cefazolin (Ansef) infusion in major surgery A. Preliminary studies There are 2 studies in the abdominal surgery population. The study by Troconiz et al studies the pharmacokinetics of a bolus dose of cefoxitin.3 The study by Suffoleta studied a postoperative continuous infusion in the postoperative colorectal group.4 B. Experimental design and methods (including data analysis) Informed consent for the study will be obtained in the PETC (Pre-anesthesia Clinic) prior to surgery. Induction and maintenance of anesthesia will be at the discretion of the attending anesthesiologist. Intraoperative analgesia will be provided at the discretion of the attending anesthesiologist and may include intravenous narcotics and/or intrathecal morphine. ### Conditions Module **Conditions:** - Plasma Concentration of Antibiotics ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Bolus infusion of antibiotics **Intervention Names:** - Drug: BOLUS INFUSION (Ancef) **Label:** BOLUS INFUSION **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Continuous infusion of antibiotics by way of infusion pump **Intervention Names:** - Drug: CONTINUOUS INFUSION (Ancef) **Label:** CONTINUOUS INFUSION **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - BOLUS INFUSION **Description:** Bolus Infusion of antibiotics **Name:** BOLUS INFUSION (Ancef) **Other Names:** - ANCEF Bolus Infusion of antibiotics **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - CONTINUOUS INFUSION **Description:** Continuous Infusion of ANCEF with infusion pump **Name:** CONTINUOUS INFUSION (Ancef) **Other Names:** - Continuous Infusion of ANCEF with infusion pump **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Plasma concentration of antibiotics during surgery **Measure:** Plasma Concentration of Antibiotics **Time Frame:** 1 Day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \> 18 years * Elective abdominal and orthopedic surgery * A patent arterial line * A patent IV line * Must be able to read and speak English Exclusion Criteria: * Subjects unable to give informed consent. * Allergy to cefazolin * Cognitively Impared * Prisoners * Pregnant females (self reported) * History of coagulopathy * Subjects presenting for emergency abdominal surgery * Creatinine clearance \< 30 ml/min * Received cefazolin within 72 hours prior to surgery **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Charlottesville **Country:** United States **Facility:** University of Virginia **State:** Virginia **Zip:** 22910-0710 #### Overall Officials **Official 1:** **Affiliation:** University of Virginia **Name:** BHIKEN NAIK, M.B. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Suffoletta TJ, Jennings HR, Oh JJ, Stephens D, Poe KL. Continuous versus intermittent infusion of prophylactic cefoxitin after colorectal surgery: a pilot study. Pharmacotherapy. 2008 Sep;28(9):1133-9. doi: 10.1592/phco.28.9.1133. **PMID:** 18752384 **Citation:** Toma O, Suntrup P, Stefanescu A, London A, Mutch M, Kharasch E. Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection. Anesth Analg. 2011 Oct;113(4):730-7. doi: 10.1213/ANE.0b013e31821fff74. Epub 2011 Jun 3. **PMID:** 21642605 **Citation:** Isla A, Troconiz IF, de Tejada IL, Vazquez S, Canut A, Lopez JM, Solinis MA, Rodriguez Gascon A. Population pharmacokinetics of prophylactic cefoxitin in patients undergoing colorectal surgery. Eur J Clin Pharmacol. 2012 May;68(5):735-45. doi: 10.1007/s00228-011-1206-1. Epub 2012 Jan 15. **PMID:** 22246211 **Citation:** Bratzler DW, Hunt DR. The surgical infection prevention and surgical care improvement projects: national initiatives to improve outcomes for patients having surgery. Clin Infect Dis. 2006 Aug 1;43(3):322-30. doi: 10.1086/505220. Epub 2006 Jun 16. **PMID:** 16804848 **Citation:** Naik BI, Roger C, Ikeda K, Todorovic MS, Wallis SC, Lipman J, Roberts JA. Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: a randomized controlled trial. Br J Anaesth. 2017 Jun 1;118(6):876-882. doi: 10.1093/bja/aex026. **PMID:** 28505360 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5687 - Name: Cefazolin - Relevance: HIGH - As Found: Retinitis Pigmentosa - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: HIGH - As Found: Initial - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000002437 - Term: Cefazolin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03561779 **Brief Title:** Clinical Trial of YYD302 (Phase3) for Treatment of Osteoarthritis of the Knee **Official Title:** A Randomized, Double-blind, Active-controlled, Multi-center, Phase 3 Study to Evaluated the Safety and Efficacy of Intraarticular Hyalurinic Acid(YYD302) for Osteoarthritis of the Knee After 12 Weeks of Treatment and Retreatment #### Organization Study ID Info **ID:** YY_YYD302_003 #### Organization **Class:** INDUSTRY **Full Name:** Yooyoung Pharmaceutical Co., Ltd. ### Status Module #### Completion Date **Date:** 2019-10-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-05-10 **Type:** ACTUAL **Last Update Submit Date:** 2021-05-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-06-14 **Type:** ACTUAL #### Start Date **Date:** 2018-02-21 **Type:** ACTUAL **Status Verified Date:** 2021-05 #### Study First Post Date **Date:** 2018-06-19 **Type:** ACTUAL **Study First Submit Date:** 2018-06-04 **Study First Submit QC Date:** 2018-06-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Yooyoung Pharmaceutical Co., Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a randomized, double-blind, active-controlled, multi-center, phase 3 study to evaluate the safety and efficacy of intraarticular hyaluronic acid(YYD302) for osteoarthritis of the knee after 12 weeks of treatment and retreatment **Detailed Description:** First Injection: A multicenter, active-controlled, randomized, evaluator and subject bllinded, parallel, phase 3 study Re-Injection: A multicenter, active-controlled, randomized, parallel ### Conditions Module **Conditions:** - Osteoarthritis, Knee **Keywords:** - Osteoarthritis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** The Subjects are injected investigational Product (YYD302 or Synovian Inj.) ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 184 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** YYD302 (2ml) **Intervention Names:** - Drug: YYD302 2ml **Label:** YYD302 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Synovian Inj. (3ml) **Intervention Names:** - Drug: Active comparator: Synovian Inj. **Label:** Synovian Inj. **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - YYD302 **Description:** YYD302 2ml **Name:** YYD302 2ml **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Synovian Inj. **Description:** Active comparator: Synovian Inj. **Name:** Active comparator: Synovian Inj. **Other Names:** - Synovian Inj. **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Weight-bearing pain(100mm-VAS) assessed by the subject **Measure:** Rate of change of the Weight-bearing pain(100mm-VAS) on 12 weeks after first injection in comparison with baseline **Time Frame:** Change of the week 12 from baseline #### Secondary Outcomes **Description:** Weight-bearing pain(100mm-VAS) assessed by the subject **Measure:** Rate of change of the Weight-bearing pain(100mm-VAS) on 2, 4 weeks after administration in comparison with baseline **Time Frame:** Change of the week 2, 4 from baseline **Description:** KOOS scales assessed by the subject **Measure:** Rate of change of the KOOS scales on the 2, 4, 12 weeks after administration in comparison with baseline **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Rest pain(100mm-VAS) assessed by the subject **Measure:** Rate of change of the rest pain(100mm-VAS) on the 2, 4, 12 weeks after administration in comparison with baseline **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Motion pain(100mm-VAS) assessed by the subject **Measure:** Rate of change of the Motion pain (100mm-VAS) on the 2, 4, 12 weeks after administration in comparison with baseline **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Patient global assessment (100mm-VAS) assessed by the subject **Measure:** Patient global assessment (100mm-VAS) on the 2, 4, 12 weeks after administration with baseline **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Patient global assessment (100mm-VAS) assessed by the investigator **Measure:** Investigator global assessment (100mm-VAS) on the 2, 4, 12 weeks after administration with baseline **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Sweeling assessed by the investigator **Measure:** Change of the swelling in the knee joint from baseline to 2, 4, 12 weeks after administration **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Tenderness on pressure assessed by the investigator **Measure:** Change of the tenderness on pressure in the knee joint from baseline to 2, 4, 12 weeks after administration **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Range of motion assessed by the investigator **Measure:** Variation of the Range Of Motion(ROM) in the knee joint on 2, 4, 12 weeks after administration with baseline **Time Frame:** Change of the week 2, 4, 12 from baseline **Description:** Responder rate of the Weight-bearing pain assessed by the investigator **Measure:** Responder rate of the Weight-bearing pain on 12 weeks in comparison with baseline **Time Frame:** Change of the week 12 from baseline **Description:** Responder rate of the OMERACT-OARSI assessed by the investigator **Measure:** Responder rate of the OMERACT-OARSI on 12 weeks in comparison with baseline **Time Frame:** Change of the week 12 from baseline **Description:** Use of rescue medication count and the total amount assessed by subject **Measure:** Use of rescue medication count and the total amount on each visit after injection **Time Frame:** Change of the each visit(2, 4, 12, 24, 36 weeks) after injection **Description:** Each outcome assessed by the investigator or subject **Measure:** The efficacy of secondary outcome 1~11 after 12 weeks(36weeks) compared with the Re-injection(24weeks) in re-injection subjects **Time Frame:** Change of the week 12 (36 weeks) after Re-injection(24weeks) **Description:** Each outcome assessed by the investigator or subject **Measure:** The efficacy of secondary outcome 1~11 after baseline compared with 2, 4, 12, 24, 36 weeks in Re-injection subjects **Time Frame:** Change of the week 2, 4, 12, 24, 36 from baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: \[Visit 1, 2 Inclusion Criteria\] 1. Males or Females 40 years and older 2. According to the clinical diagnosis standard of the American College of Rheumatology (ACR), someone, diagnosed as a single/both sides of osteoarthritis, who corresponds to over 3 conditions of followings. 1) Over 50 years of age 2) Less than 30 minutes of morning stiffness 3) Crepitus on active motion 4) 4 bony tenderness 5) Bony enlargement 6) Nopalpable warmth of synvium 3. Within 6 months from screening visit, someone who diagnosed with Kellgren \& Lawrence Grade I\~III by the radioactive examination. 4. By the Weight-bearing pain(100mm-VAS) examination, someone who has a outcome of the single or both sides of the osteoarthritis is over 40mm 5. Patient (No-responder) who has experienced steady pain in spite of dosing NSAIDs or other pain-killers in the past. 6. Patient who can walk by themselves without helper like cane or walker etc. (If the patient who has used helper routinely from previous 6 months, evaluating the patient including the helper is possible. In this case, patient needs to use same helper continuously by end of the clinical trial test.) 7. Patient who agrees to participate in this clinical trial by themselves. \[Visit 6, 7 Inclusion criteria\] 1. According to the clinical diagnosis standard of the American College of Rheumatology (ACR), someone, diagnosed as a single/both sides of osteoarthritis, who corresponds to over 3 conditions of followings. 1. Over 50 years of age 2. Less than 30 minutes of morning stiffness 3. Crepitus on active motion 4. 4 bony tenderness 5. Bony enlargement 6. Nopalpable warmth of synvium 2. At Re-screening visit, someone who diagnosed with Kellgren \& Lawrence Grade I\~III by the radioactive examination. 3. Patient who can walk by themselves without helper like cane or walker etc. (If the patient who has used helper routinely from previous 6 months, evaluating the patient including the helper is possible. In this case, patient needs to use same helper continuously by end of the clinical trial test.) 4. Patient who are confirmed for Responder by efficacy at visit 5. Exclusion Criteria: 1. Someone who has BMI≥32kg/m² at the screening visit. 2. Patient who has an experience dosing psychoactive drug, narcotic analgesic which can have an effect on pain sense over 3 months habitually. 3. Patient who has been administrated gastrointestinal drug(for example H₂-blockers, misoprostol or proton pump inhibitors) regularly, who can't stop injecting for clinical study period. 4. Patient has attended abnormal values from screening test(2 times excess at upper limit of the normal values at ALT, AST, BUN, Serum Creatinine). 5. Patient who has rheumarthritis or other inflammatory metabolic arthritis. 6. Patients having serious gastrointestinal, liver, renal, heart disease. 7. When the inflammatory disease is occurred on joint area to patient like septic arthritis. 8. Patients having skin ailment at the injecting site of the joint region. 9. Patients having secondary osteoarthritis according to the Ochronosis, Hemochromatosis or systemic disease. 10. Patients who have severe pain like Sudek's atrophy, Paget's disease, Spinal disc herniation. 11. Poly-articular patients who have suffered seriously by osteoarthritis at other parts affect judge of the knee joint pain. 12. Patients who diagnosed clear interval disappearance at the knee joint by X-ray. 13. Patients who were administrated below drugs before baseline visit. 1) Patients who were injected HA at the target knee joint or other parts of knee joint in recent 9 months. 2) Patients who were injected steroids into the intra-articular knee joint in recent 3 months 3) Patients who were administrated steroids systemically by the oral medication (But, except inhalation) 4) Patients who were administerated Osteoarthritis nutrition such as glucosamine/chondroichin sulfate or physical therapy or herbal remedy(acupuncture, yellowish swelling, moxa cautery) for the purpose of pain relief in recent 2 weeks 5) Patients who have administerated steroid/No-steriod NSAIDs or other pain relief drugs (patch or other external medicine) in recents 2 weeks except Acetaminophen or below 300mg/day of Asprin 14. Patients who have joint effusion trouble were judged as a positive by tests like Patella tap test. 15. Patients who have target knee joint gotten surgical operation history including Arthroscopy within past one year (In case of having other side of knee joint or hip joint gotten surgical operation history, excepting the patients if there is possibility which can influence the target knee joint's appraisal. 16. Patients who have an operation history about target knee joint. 17. Patients who do the height weight aerobic exercise or anaerobic exercise. 18. Patients who need to be administrated anticoagulant agent together(But, except 300mg daily dose aspirin) 19. Patients who have hypersensitivity history about Investigational Product. 20. In the midst of women in their childbearing years, patients who disagree to do \* contraception by medically permitted method for 12 weeks from administrating investigational product. * The contraception by medically permitted method: Condom, In case of using injection or insertion, In case of installing a intrauterine contraception device etc. 21. Pregnant and lactating women 22. Patients who were injected other investigational product over a time within 30 days before participated in this clinical trail. 23. Besides that, the patients who have difficulty to be participated in this clinical trial continuously by Principle Investigator (PI)'s decision. * Exclusion criteria for Re-injection is except for 13-1) Re-injection date is followed by visit 7. **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Samsung Medical Center #### Overall Officials **Official 1:** **Affiliation:** Samsung Medical Center, Department of Internal Medicine **Name:** Chul-Won Ha, M.D **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Park YG, Ha CW, Yoo JH, Lee WS, Lee HJ, In Y, Bae KC, Shon OJ, Kim YM, Seon JK, Song SJ, Chang CB, Kim JM, Kim CW, Kim DH, Bae JH. Intra-Articular Injection of a Novel DVS Cross-Linked Hyaluronic Acid Manufactured by Biological Fermentation (YYD302) in Patients With Knee Osteoarthritis: A Double-Blind, Randomized, Multicenter, Noninferiority Study. Clin Ther. 2021 Nov;43(11):1843-1860. doi: 10.1016/j.clinthera.2021.09.005. Epub 2021 Nov 1. **PMID:** 34736768 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Osteoarthritis, Knee - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis - ID: D000020370 - Term: Osteoarthritis, Knee ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05669079 **Brief Title:** Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allo-HSCT **Official Title:** Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allogenic Hematopoietic Stem Cell Transplantation #### Organization Study ID Info **ID:** SOOCHOW-HY-2022-12-15 #### Organization **Class:** OTHER **Full Name:** The First Affiliated Hospital of Soochow University ### Status Module #### Completion Date **Date:** 2026-11-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-09 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-08 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-08-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-08-01 **Type:** ESTIMATED **Status Verified Date:** 2022-12 #### Study First Post Date **Date:** 2022-12-30 **Type:** ACTUAL **Study First Submit Date:** 2022-12-19 **Study First Submit QC Date:** 2022-12-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** The First Affiliated Hospital of Soochow University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This randomized trial aimed at validating the efficacy and safety of low-dose decitabine, together with umbilical cord blood in PGF post allo-HSCT patients. **Detailed Description:** Poor graft function (PGF), defined by the presence of multilineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (allo-HSCT). Emerging evidence demonstrates that the inadequate stem cells infusion, bone marrow microenvironment and immune dysregulation play a crucial role in maintaining and regulating hematopoiesis. Current therapies remain debatable, including selected CD34+ cells infusion, mesenchymal stromal cells infusion, prophylactic N-acetyl cysteine administration, etc. Thereafter, the investigators conduct a randomized trial aiming at validating the efficacy and safety of low-dose decitabine, together with umbilical cord blood in PGF post allo-HSCT patients. Patients were eligible if they were diagnosed as PGF at day 28 post-HSCT or later. PGF was defined as two or three cytopenias, absolute neutrophil count ≤ 1.5 × 109/L, platelet count ≤ 30 × 109/L, hemoglobin ≤ 85g/L, lasting for more than 14 consecutive weeks, in the presence of full donor chimerism and primary disease in remission without severe graft-versus- host disease (GVHD) and relapse. Patients with the following conditions or diagnoses were excluded: allergic to decitabine or any components of frozen preservation of umbilical cord blood; active infections; uncontrolled GVHD; severe organ dysfunction; relapse of underlying malignancies; graft failure. Patients were also excluded if they had received decitabine or participated in other clinical trials within one month before screening. Hematological improvement is defined as recovery of two or three blood lineages: absolute neutrophil count\>1.5 × 109/L, platelet count\>30 × 109/L, hemoglobin\>85g/L, without G-CSF, red blood cell or platelet infusion. Hematological response is defined as recovery of three blood lineages: absolute neutrophil count\>2.5 × 109/L, platelet count\>60 × 109/L, hemoglobin\>100g/L, without G-CSF, red blood cell or platelet infusion. No response: failed to achieve hematological improvement or response. ### Conditions Module **Conditions:** - Poor Graft Function ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8) **Intervention Names:** - Drug: decitabine - Biological: umbilical cord blood - Drug: Granulocyte-colony stimulating factor - Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist - Drug: Recombinant human erythropoietin **Label:** Arm A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Supportive therapy: G-CSF for patients with absolute neutrophil count ≤ 1.5 × 109/L, rhTPO/TPO-R with platelet count ≤ 30 × 109/L, EPO with hemoglobin ≤ 85g/L. **Intervention Names:** - Drug: Granulocyte-colony stimulating factor - Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist - Drug: Recombinant human erythropoietin **Label:** Arm B **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm A **Description:** 15 mg/m2 daily intravenously for consecutive 3 days **Name:** decitabine **Other Names:** - Dec **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Arm A **Description:** MNC ≥ 3\*108 cells; HLA compatibility ≥ 5/6 **Name:** umbilical cord blood **Other Names:** - UCB **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - Arm A - Arm B **Description:** Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L **Name:** Granulocyte-colony stimulating factor **Other Names:** - G-CSF **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Arm A - Arm B **Description:** Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L **Name:** Recombinant human thrombopoietin / thrombopoietin receptor agonist **Other Names:** - rhTPO/TPO-RA **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - Arm A - Arm B **Description:** Recombinant human erythropoietin will be used when hemoglobin ≤ 85 g/L **Name:** Recombinant human erythropoietin **Other Names:** - EPO **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The rate of hematological improvement and hematological response of 2 arms **Measure:** The treatment response **Time Frame:** day +28 **Description:** The rate of overall survival **Measure:** Survival **Time Frame:** 1 year #### Secondary Outcomes **Description:** Number of participants with granulopoiesis, erythropoiesis and megakaryopoiesis recovery of bone marrow **Measure:** Bone marrow recovery **Time Frame:** day +28 **Description:** The rate of relapse and GVHD **Measure:** relapse and GVHD **Time Frame:** 3-month **Description:** The rate of event free survival **Measure:** Event free survival **Time Frame:** 1-year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Diagnosed as PGF at day 28 post-HSCT or later. PGF was defined as two or three cytopenias, absolute neutrophil count ≤ 1.5 × 109/L, platelet count ≤ 30 × 109/L, hemoglobin ≤ 85g/L, lasting for more than 2 consecutive weeks; 2. Full donor chimerism; 3. Primary disease in remission; 4. No severe GVHD and relapse. Exclusion Criteria: 1. Allergic to decitabine or any components of frozen preservation of umbilical cord blood; 2. Active infections; 3. Uncontrolled GVHD; 4. Severe organ dysfunction; 5. Relapse of underlying malignancies; 6. Graft failure; 7. Received decitabine or participated in other clinical trials within one month before screening. **Maximum Age:** 65 Years **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** tangyaqiong@suda.edu.cn **Name:** Yaqiong Tang **Phone:** 18896588075 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** The First Affiliated Hospital of Soochow University **Name:** Yue Han **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Alchalby H, Yunus DR, Zabelina T, Ayuk F, Kroger N. Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transplant. 2016 Sep;51(9):1223-7. doi: 10.1038/bmt.2016.98. Epub 2016 Apr 18. **PMID:** 27088376 **Citation:** Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, Bacigalupo A. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006 Jul;91(7):935-40. **PMID:** 16818281 **Citation:** Prabahran A, Koldej R, Chee L, Ritchie D. Clinical features, pathophysiology, and therapy of poor graft function post-allogeneic stem cell transplantation. Blood Adv. 2022 Mar 22;6(6):1947-1959. doi: 10.1182/bloodadvances.2021004537. **PMID:** 34492685 **Citation:** Tang Y, Chen J, Liu Q, Chu T, Pan T, Liang J, He XF, Chen F, Yang T, Ma X, Wu X, Hu S, Cao X, Hu X, Hu J, Liu Y, Qi J, Shen Y, Ruan C, Han Y, Wu D. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021 Mar 9;5(5):1250-1258. doi: 10.1182/bloodadvances.2020002790. **PMID:** 33646303 **Citation:** Han Y, Tang Y, Chen J, Liang J, Ye C, Ruan C, Wu D. Low-Dose Decitabine for Patients With Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Therapeutic Study. JAMA Oncol. 2015 May;1(2):249-51. doi: 10.1001/jamaoncol.2014.316. No abstract available. **PMID:** 26181032 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000000276 - Term: Adjuvants, Immunologic - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000006397 - Term: Hematinics ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: Hemat - Name: Hematinics ### Intervention Browse Module - Browse Leaves - ID: M1697 - Name: Decitabine - Relevance: HIGH - As Found: Above - ID: M207501 - Name: Chrysarobin - Relevance: LOW - As Found: Unknown - ID: M1945 - Name: Lenograstim - Relevance: HIGH - As Found: Indicated - ID: M314 - Name: Epoetin Alfa - Relevance: HIGH - As Found: Peak - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M9485 - Name: Hematinics - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077209 - Term: Decitabine - ID: D000068817 - Term: Epoetin Alfa - ID: D000078224 - Term: Lenograstim ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02877979 **Brief Title:** Evaluate the Safety & Assess Local and Systemic PK of DS003 Vaginal Tablets Administered to Healthy HIV-negative Women **Official Title:** A Double-blind, Randomised, Placebo-controlled, Dose Escalation Trial to Evaluate the Safety and to Assess Local and Systemic Pharmacokinetics of DS003 Vaginal Tablets Administered to Healthy HIV-negative Women #### Organization Study ID Info **ID:** IPM 042 #### Organization **Class:** INDUSTRY **Full Name:** International Partnership for Microbicides, Inc. ### Status Module #### Completion Date **Date:** 2016-08-26 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-24 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-08-26 **Type:** ACTUAL #### Start Date **Date:** 2015-11-18 **Type:** ACTUAL **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2016-08-25 **Type:** ESTIMATED **Study First Submit Date:** 2016-07-25 **Study First Submit QC Date:** 2016-08-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** International Partnership for Microbicides, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** A double-blind, randomised, placebo-controlled, dose escalation trial to evaluate the safety and to assess local and systemic pharmacokinetics of ds003 vaginal tablets administered to healthy HIV-negative women. ### Conditions Module **Conditions:** - HIV ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 36 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17. **Intervention Names:** - Drug: DS003 vaginal tablet **Label:** DS003 vaginal tablet **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17. **Intervention Names:** - Drug: Placebo **Label:** placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - DS003 vaginal tablet **Description:** The trial will be conducted in three cohorts of 12 women each. In each cohort, participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17. In each cohort, therefore, 9 participants will receive DS003 vaginal tablets and 3 participants will receive placebo vaginal tablets. **Name:** DS003 vaginal tablet **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - placebo **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Gynaecological assessments, including pelvic examination and colposcopy **Measure:** To evaluate the safety of three escalating doses of DS003 (1 mg, 3 mg and 10 mg), administered in a vaginal tablet formulation, to healthy, HIV-negative female volunteers. **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** Measurement of DS003 concentrations in plasma, vaginal fluids and cervical tissue collected at various time points after administration of the vaginal tablet(s). **Measure:** To assess the local (vaginal fluids) and systemic (plasma) DS003 PK profile and the 24 hour cervical tissue concentration when administered in three escalating doses of a vaginal tablet formulation. **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Women must meet all of the following criteria to be eligible for enrolment: 1. Women ≥ 18 and ≤ 45 years of age who can give written informed consent 2. BMI of ≥ 18 and \< 30 kg/m2 3. Vital signs within normal limits and no clinically significant ECG findings 4. Available for all visits and consent to follow all procedures scheduled for the trial 5. Healthy, based on medical history, vital signs, physical examination, urinalysis (dipstick and microscopy), laboratory evaluations for genital infections (bacterial vaginosis, gonorrhoea, chlamydia and trichomonas) and laboratory evaluations for haematology and biochemistry 6. HIV-negative as determined by an HIV test at the time of screening 7. On a stable form of contraception, defined as: * A stable oral contraceptive regimen for at least 2 months prior to enrolment, OR * Transdermal contraceptive patch for at least 3 months prior to enrolment, OR * Subcutaneous implant inserted at least 3 months prior to enrolment, OR * Long-acting progestins for at least 2 consecutive injections, OR An IUD inserted (with no vaginal or gynaecological complaints associated with its use) at least 3 months prior to enrolment, OR * Have undergone surgical sterilisation at least 3 months prior to enrolment AND be willing to use oral contraceptives if necessary to delay menstruation while taking part in the trial 8. Upon pelvic examination and colposcopy at screening and visual inspection of the cervix at the time of enrolment, the cervix and vagina appear normal as determined by the Investigator 9. Asymptomatic for urogenital infections at the time of screening (if a woman is diagnosed with any curable STI, either clinically or by laboratory test at the time of screening, she must complete the full course of treatment and have a healthy genital tract before being considered for potential re-screening) 10. Willing to refrain from the use of topical vaginal medications, vaginal products or objects, including tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches, lubricants, vibrators/dildos, and drying agents for 7 days prior to enrolment and for the duration of the trial 11. Documentation of no abnormality on cervical cytology, including grossly bloody smear, within 90 days prior to screening 12. Willing to refrain from participation in any other research trial for the duration of this trial 13. Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures, e.g. by home visit or telephone, or via family or close neighbour contacts (confidentiality to be maintained) 14. Willing to agree to abstain from all the following for a total of 2 days (48 hours) prior to each trial visit, and for a total of 3 days (72 hours) after the biopsy procedure: Penile-vaginal intercourse • Oral contact with her genitalia 15. Hepatitis B and C negative at the time of screening Exclusion Criteria: Women who meet any of the exclusion criteria below are not eligible: 1. Currently pregnant or had their last pregnancy outcome within 3 months prior to screening 2. Currently breast-feeding 3. Currently or within 2 months of participation in any other clinical research trial involving investigational or marketed products prior to screening 4. Untreated symptomatic urogenital infections, e.g. urinary tract or other sexually transmitted infections, or other gynaecological conditions such as vaginal itching, pain, or discharge, prior to enrolment 5. Have a Grade 2 or higher pelvic examination finding, according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events; Addendum 1 Female Genital Grading Table for Use in Microbicide Studies 6. History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence 7. Current vulvar or vaginal symptoms/abnormalities that could influence the trial results 8. Cervical cytology at screening that requires cryotherapy, biopsy, treatment, or further evaluation 9. Symptomatic genital herpes simplex virus (HSV) infection or a history of genital herpetic infection 10. Any Grade 2, 3 or 4 haematology, biochemistry or urinalysis laboratory abnormality at baseline (screening) according to the current version of the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 11. Unexplained, abnormal bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrolment 12. Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex 13. Any serious acute, chronic or progressive disease (e.g. any known history of neoplasm, cancer, diabetes, epilepsy, cardiac disease, autoimmune disease, HIV, AIDS, or blood dyscrasias), or signs of cardiac disease, renal failure, or severe malnutrition 14. Have undergone a hysterectomy 15. History of drug or substance abuse within 1 year of enrolment 16. Use of tobacco within 6 months of enrolment 17. Not willing to abstain from alcohol from 14 days prior to enrolment until completion of trial participation 18. Have had significant blood loss, or have donated or received one or more units of blood within 6 weeks prior to enrolment 19. Have a positive urine drug or positive breath alcohol screen at screening or enrolment 20. Any disease or condition (medical or surgical) that might compromise haematological, cardiovascular, pulmonary, renal, gastrointestinal, or central nervous system function; or any other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or that would place the participant at increased risk, as determined by the Investigator 21. Regular use of, or have received, any concomitant prescription, over-the-counter, or herbal medications or nutritional supplements within 14 days prior to enrolment 22. Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### IPD Sharing Statement Module **IPD Sharing:** YES ### References Module #### References **Citation:** Herrera C, Harman S, Aldon Y, Rogers P, Armanasco N, Ziprin P, Stieh D, Nuttall J, Shattock RJ. The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate. AIDS. 2021 Oct 1;35(12):1907-1917. doi: 10.1097/QAD.0000000000002974. **PMID:** 34101626 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02595879 **Brief Title:** Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal Cancer **Official Title:** Phase I Dose-Escalation Bioavailability Study of Oral Triapine in Combination With Concurrent Chemoradiation for Locally Advanced Cervical Cancer (LACC) and Vaginal Cancer #### Organization Study ID Info **ID:** NCI-2015-01907 #### Organization **Class:** NIH **Full Name:** National Cancer Institute (NCI) #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2015-01907 **Type:** REGISTRY **ID:** HCC 15-157 **ID:** UPCI 15-157 **ID:** 15-157 **Domain:** University of Pittsburgh Cancer Institute LAO **ID:** 9892 **Type:** OTHER **Domain:** CTEP **ID:** 9892 **Type:** OTHER **ID:** UM1CA186690 **Link:** https://reporter.nih.gov/quickSearch/UM1CA186690 **Type:** NIH ### Status Module #### Completion Date **Date:** 2024-11-26 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-06 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-05 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-10-31 **Type:** ACTUAL #### Start Date **Date:** 2019-09-18 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2015-11-04 **Type:** ESTIMATED **Study First Submit Date:** 2015-11-03 **Study First Submit QC Date:** 2015-11-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Cancer Institute (NCI) #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** This phase I trial studies the side effects and best dose of triapine when given with radiation therapy and cisplatin in treating patients with stage IB2-IVA cervical or vaginal cancer. Triapine may stop the growth of cancer cells by blocking an enzyme needed for cell growth. Cisplatin is a drug used in chemotherapy that kills cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Adding triapine to standard treatment with cisplatin and radiation therapy may kill more cancer cells. **Detailed Description:** PRIMARY OBJECTIVES: I. To determine the maximum tolerable dose (MTD) and recommended phase II dose (RP2D) of oral triapine when used in combination with cisplatin plus radiation therapy. II. To determine the oral bioavailability of triapine. III. To describe the pharmacokinetics (PK) of oral and intravenous triapine. SECONDARY OBJECTIVES: I. To determine whether the metabolic complete response (mCR) rate of oral triapine in combination with cisplatin chemoradiation using fludeoxyglucose F 18 (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) at post-therapy (3-month) is at least 70%. II. To determine clinical overall response rate, progression-free survival, and overall survival. III. To determine the correlation of methemoglobin proportion (%) and triapine pharmacokinetic exposure. EXPLORATORY OBJECTIVE: I. To determine whether active human immunodeficiency virus (HIV) antiretroviral therapy impacts the antitumor activity of triapine. OUTLINE: This is a dose-escalation study of triapine. Patients undergo pelvic external beam radiation therapy (EBRT) or intensity modulated radiation therapy (IMRT) 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of low dose rate (LDR) brachytherapy in week 6 or 5 fractions of high dose rate (HDR) brachytherapy at week 4 or 5. Patients also receive triapine intravenously (IV) over 120 minutes on day 1 and orally (PO) on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo magnetic resonance imaging (MRI) and FDG-PET/CT during follow-up. ### Conditions Module **Conditions:** - Advanced Cervical Adenocarcinoma - Advanced Cervical Adenosquamous Carcinoma - Advanced Cervical Squamous Cell Carcinoma - Advanced Vaginal Adenocarcinoma - Advanced Vaginal Adenosquamous Carcinoma - Advanced Vaginal Squamous Cell Carcinoma - Stage IB2 Cervical Cancer AJCC v6 and v7 - Stage II Cervical Cancer AJCC v7 - Stage II Vaginal Cancer AJCC v6 and v7 - Stage III Vaginal Cancer AJCC v6 and v7 - Stage IIIB Cervical Cancer AJCC v6 and v7 - Stage IVA Cervical Cancer AJCC v6 and v7 - Stage IVA Vaginal Cancer AJCC v6 and v7 ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 22 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients undergo pelvic EBRT or IMRT 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of LDR brachytherapy in week 6 or 5 fractions of HDR brachytherapy at week 4 or 5. Patients also receive triapine IV over 120 minutes on day 1 and PO on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo MRI and FDG-PET/CT during follow-up. **Intervention Names:** - Procedure: Biospecimen Collection - Radiation: Brachytherapy - Drug: Cisplatin - Procedure: Computed Tomography - Radiation: External Beam Radiation Therapy - Other: Fludeoxyglucose F-18 - Radiation: High-Dose Rate Brachytherapy - Radiation: Intensity-Modulated Radiation Therapy - Procedure: Magnetic Resonance Imaging - Other: Pharmacological Study - Procedure: Positron Emission Tomography - Drug: Triapine **Label:** Treatment (triapine, chemoradiation) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo collection of blood samples **Name:** Biospecimen Collection **Other Names:** - Biological Sample Collection - Biospecimen Collected - Specimen Collection **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo LDR brachytherapy **Name:** Brachytherapy **Other Names:** - Brachytherapy, NOS - Internal Radiation - Internal Radiation Brachytherapy - Internal Radiation Therapy - Radiation Brachytherapy - Radiation, Internal **Type:** RADIATION #### Intervention 3 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Given IV **Name:** Cisplatin **Other Names:** - Abiplatin - Blastolem - Briplatin - CDDP - Cis-diammine-dichloroplatinum - Cis-diamminedichloridoplatinum - Cis-diamminedichloro Platinum (II) - Cis-diamminedichloroplatinum - Cis-dichloroammine Platinum (II) - Cis-platinous Diamine Dichloride - Cis-platinum - Cis-platinum II - Cis-platinum II Diamine Dichloride - Cismaplat - Cisplatina - Cisplatinum - Cisplatyl - Citoplatino - Citosin - Cysplatyna - DDP - Lederplatin - Metaplatin - Neoplatin - Peyrone's Chloride - Peyrone's Salt - Placis - Plastistil - Platamine - Platiblastin - Platiblastin-S - Platinex - Platinol - Platinol- AQ - Platinol-AQ - Platinol-AQ VHA Plus - Platinoxan - Platinum - Platinum Diamminodichloride - Platiran - Platistin - Platosin **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo FDG-PET/CT **Name:** Computed Tomography **Other Names:** - CAT - CAT Scan - Computed Axial Tomography - Computerized Axial Tomography - Computerized axial tomography (procedure) - Computerized Tomography - CT - CT Scan - tomography **Type:** PROCEDURE #### Intervention 5 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo pelvic EBRT **Name:** External Beam Radiation Therapy **Other Names:** - Definitive Radiation Therapy - EBRT - External Beam Radiation - External Beam Radiotherapy - External Beam Radiotherapy (conventional) - External Beam RT - external radiation - External Radiation Therapy - external-beam radiation - Radiation, External Beam - Teleradiotherapy - Teletherapy - Teletherapy Radiation **Type:** RADIATION #### Intervention 6 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo FDG-PET/CT **Name:** Fludeoxyglucose F-18 **Other Names:** - 18FDG - FDG - Fludeoxyglucose (18F) - fludeoxyglucose F 18 - Fludeoxyglucose F18 - Fluorine-18 2-Fluoro-2-deoxy-D-Glucose - Fluorodeoxyglucose F18 **Type:** OTHER #### Intervention 7 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo HDR brachytherapy **Name:** High-Dose Rate Brachytherapy **Other Names:** - Brachytherapy, High Dose - HDR - High dose brachytherapy (procedure) **Type:** RADIATION #### Intervention 8 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo IMRT **Name:** Intensity-Modulated Radiation Therapy **Other Names:** - IMRT - Intensity modulated radiation therapy (procedure) - Intensity Modulated RT - Intensity-Modulated Radiotherapy - Radiation, Intensity-Modulated Radiotherapy **Type:** RADIATION #### Intervention 9 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo MRI **Name:** Magnetic Resonance Imaging **Other Names:** - Magnetic Resonance - Magnetic resonance imaging (procedure) - Magnetic Resonance Imaging Scan - Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance - MR - MR Imaging - MRI - MRI Scan - MRIs - NMR Imaging - NMRI - Nuclear Magnetic Resonance Imaging - sMRI - Structural MRI **Type:** PROCEDURE #### Intervention 10 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Correlative studies **Name:** Pharmacological Study **Type:** OTHER #### Intervention 11 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Undergo FDG-PET/CT **Name:** Positron Emission Tomography **Other Names:** - Medical Imaging, Positron Emission Tomography - PET - PET Scan - Positron emission tomography (procedure) - Positron Emission Tomography Scan - Positron-Emission Tomography - proton magnetic resonance spectroscopic imaging - PT **Type:** PROCEDURE #### Intervention 12 **Arm Group Labels:** - Treatment (triapine, chemoradiation) **Description:** Given IV and PO **Name:** Triapine **Other Names:** - 3-aminopyridine-2-carboxaldehyde thiosemicarbazone - 3-AP - 3-Apct - OCX-0191 - OCX-191 - OCX191 - PAN-811 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** MTD is defined as the dose level where \< 2/6 DLTs are observed. DLT will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (version 5.0 beginning April 1, 2018). **Measure:** Incidence of dose-limiting toxicity (DLT) to determine maximum tolerated dose (MTD) **Time Frame:** 5 weeks **Description:** The oral bioavailability of the oral form of the triapine will be estimated with corresponding 95% confidence interval (CI). **Measure:** Oral bioavailability of the oral form of the triapine **Time Frame:** Days 1 and 11 #### Secondary Outcomes **Description:** Toxicity will be evaluated using the NCI CTCAE version 4.0 (version 5.0 beginning April 1, 2018). The rate of DLT at maximum tolerated dose will be calculated and the exact 95% CI will be provided. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. All DLTs and other serious (\>= grade 3) events will be described on a patient-by-patient basis; descriptions will include dose level and any relevant baseline data. Statistics on the number of cycles received by patients and any dose reductions will also be tabulated. **Measure:** Incidence of toxicity **Time Frame:** Up to 3 months post-treatment **Description:** The mCR rate at recommended phase 2 dose will be calculated with corresponding 95% CI. **Measure:** Fludeoxyglucose F 18-Positron emission tomography computed tomography metabolic complete response (mCR) rate **Time Frame:** 3 months post-treatment **Description:** The overall response rate at recommended phase II dose will be calculated with corresponding 95% exact CI. **Measure:** Clinical overall response **Time Frame:** Up to 5 years from off-treatment date **Description:** Will be analyzed using the Kaplan-Meier's method. Median survival time will be reported with corresponding 95% CIs. **Measure:** Overall survival **Time Frame:** Up to 5 years from off-treatment date **Description:** Will be analyzed using the Kaplan-Meier's method. Median survival time will be reported with corresponding 95% CIs. **Measure:** Progression free survival **Time Frame:** Up to 5 years from off-treatment date **Description:** Standard PK parameters will be determined and will include maximum concentration, time to maximum concentration, drug clearance, steady state concentration, and half-life. These parameters will be descriptively reported. The association of methemoglobin proportion (%) and PK parameters will be evaluated by Spearman correlation coefficients. **Measure:** Pharmacokinetics (PK) parameters **Time Frame:** Baseline (prior to infusion); 30, 60, 90, 110, 2 hours 30 minutes, and 3 hours after the start of the infusion ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient has a new, untreated histologic diagnosis of stage IB2 (\> 5 cm), II, IIIB, IIIC or IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix or stage II-IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the vagina not amenable to curative surgical resection alone; the presence or absence of lymph node metastasis will be based on pre-therapy 18F-FDG PET/CT; the patient must be able to tolerate imaging requirements of an 18F-FDG PET/CT scan * Age \>= 18 years old * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Life expectancy greater than 6 months * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelets \>= 100 x 10\^9/L * Hemoglobin (Hgb) \>= 10.0 g/dL (blood transfusions to reach this amount are allowed) * Serum creatinine =\< 1.5 mg/dL to receive weekly cisplatin * If serum creatinine is between 1.5 and 1.9 mg/dL, patients are eligible for cisplatin if the estimated creatinine clearance (CCr) is \> 30 ml/min (for the purpose of estimating the CCr, the formula of Cockcroft and Gault for females should be used) * Total serum bilirubin =\< 1.5 x upper limit of normal (ULN) (in patients with known Gilbert syndrome, a total bilirubin =\< 3.0 x ULN, with direct bilirubin =\< 1.5 x ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN * Able to take oral medication * Not pregnant and not breastfeeding; the effects of triapine on the developing human fetus are unknown; for this reason as well as because heterocyclic carboxaldehydethiosemicarbazones and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; patient must have documented negative urine pregnancy test must be resulted within 7 days before initiating protocol therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with triapine, breastfeeding should be discontinued if the mother is treated with triapine; these potential risks may also apply to other agents used in this study * For HIV and hepatitis B/C (HEPB/C): * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for the dose escalation portion of this trial; for those patients who are enrolled in the HIV positive (+) expansion cohort, they must be HIV infected and be on retroviral therapy with an undetectable viral load within 6 months of enrollment * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured; for patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Able to understand and willingness to sign a written informed consent document Exclusion Criteria: * Patient has had a prior invasive malignancy diagnosed within the last three years (except \[1\] non-melanoma skin cancer or \[2\] prior in situ carcinoma of the cervix) * Patients are excluded if they have received prior pelvic radiotherapy for any reason that would contribute radiation dose that would exceed tolerance of normal tissues at the discretion of the treating physician * Patients receiving any other investigational agents * Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded due to an inability to administer the antidote for methemoglobinemia, methylene blue; pre-registration testing for G6PD is at the investigator's discretion and is not required for study enrollment * Patients who are taking any medication associated with methemoglobinemia; medication must be discontinued and must have a washout period of 4 halflives or 4 weeks, whichever is shorter * History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or cisplatin * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; known inadequately controlled hypertension; significant pulmonary disease including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary reserve; or psychiatric illness/social situations that would limit compliance with study requirements * Patients with uncontrolled diabetes mellitus (fasting blood glucose controlled by medication, =\< 200 mg/dL allowed) * Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy following radiation as part of their cervical cancer treatment are ineligible * Patients scheduled to be treated with adjuvant consolidation chemotherapy at the conclusion of their standard chemoradiation **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham Cancer Center **State:** Alabama **Zip:** 35233 **Location 2:** **City:** Los Angeles **Country:** United States **Facility:** Los Angeles County-USC Medical Center **State:** California **Zip:** 90033 **Location 3:** **City:** Los Angeles **Country:** United States **Facility:** USC / Norris Comprehensive Cancer Center **State:** California **Zip:** 90033 **Location 4:** **City:** Pasadena **Country:** United States **Facility:** Keck Medical Center of USC Pasadena **State:** California **Zip:** 91105 **Location 5:** **City:** Fairway **Country:** United States **Facility:** University of Kansas Clinical Research Center **State:** Kansas **Zip:** 66205 **Location 6:** **City:** Kansas City **Country:** United States **Facility:** University of Kansas Cancer Center **State:** Kansas **Zip:** 66160 **Location 7:** **City:** Overland Park **Country:** United States **Facility:** University of Kansas Hospital-Indian Creek Campus **State:** Kansas **Zip:** 66211 **Location 8:** **City:** Westwood **Country:** United States **Facility:** University of Kansas Hospital-Westwood Cancer Center **State:** Kansas **Zip:** 66205 **Location 9:** **City:** Lexington **Country:** United States **Facility:** University of Kentucky/Markey Cancer Center **State:** Kentucky **Zip:** 40536 **Location 10:** **City:** Ann Arbor **Country:** United States **Facility:** University of Michigan Comprehensive Cancer Center **State:** Michigan **Zip:** 48109 **Location 11:** **City:** Detroit **Country:** United States **Facility:** Wayne State University/Karmanos Cancer Institute **State:** Michigan **Zip:** 48201 **Location 12:** **City:** Farmington Hills **Country:** United States **Facility:** Weisberg Cancer Treatment Center **State:** Michigan **Zip:** 48334 **Location 13:** **City:** New Brunswick **Country:** United States **Facility:** Rutgers Cancer Institute of New Jersey **State:** New Jersey **Zip:** 08903 **Location 14:** **City:** Oklahoma City **Country:** United States **Facility:** University of Oklahoma Health Sciences Center **State:** Oklahoma **Zip:** 73104 **Location 15:** **City:** Pittsburgh **Country:** United States **Facility:** University of Pittsburgh Cancer Institute (UPCI) **State:** Pennsylvania **Zip:** 15232 **Location 16:** **City:** Charlottesville **Country:** United States **Facility:** University of Virginia Cancer Center **State:** Virginia **Zip:** 22908 **Location 17:** **City:** Richmond **Country:** United States **Facility:** Virginia Commonwealth University/Massey Cancer Center **State:** Virginia **Zip:** 23298 #### Overall Officials **Official 1:** **Affiliation:** University of Pittsburgh Cancer Institute LAO **Name:** Sarah E Taylor **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000018307 - Term: Neoplasms, Squamous Cell - ID: D000014594 - Term: Uterine Neoplasms - ID: D000005833 - Term: Genital Neoplasms, Female - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000002577 - Term: Uterine Cervical Diseases - ID: D000014591 - Term: Uterine Diseases - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases - ID: D000014623 - Term: Vaginal Diseases - ID: D000018193 - Term: Neoplasms, Complex and Mixed ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: HIGH - As Found: Squamous Cell Carcinoma - ID: M5830 - Name: Uterine Cervical Neoplasms - Relevance: HIGH - As Found: Cervical Cancer - ID: M3585 - Name: Adenocarcinoma - Relevance: HIGH - As Found: Adenocarcinoma - ID: M17373 - Name: Vaginal Neoplasms - Relevance: HIGH - As Found: Vaginal Cancer - ID: M20342 - Name: Carcinoma, Adenosquamous - Relevance: HIGH - As Found: Adenosquamous Carcinoma - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M20451 - Name: Neoplasms, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M17342 - Name: Uterine Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8945 - Name: Genital Neoplasms, Female - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5825 - Name: Uterine Cervical Diseases - Relevance: LOW - As Found: Unknown - ID: M17339 - Name: Uterine Diseases - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M17371 - Name: Vaginal Diseases - Relevance: LOW - As Found: Unknown - ID: T5829 - Name: Vaginal Cancer - Relevance: HIGH - As Found: Vaginal Cancer ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000002294 - Term: Carcinoma, Squamous Cell - ID: D000000230 - Term: Adenocarcinoma - ID: D000002583 - Term: Uterine Cervical Neoplasms - ID: D000014625 - Term: Vaginal Neoplasms - ID: D000018196 - Term: Carcinoma, Adenosquamous ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000019275 - Term: Radiopharmaceuticals - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000963 - Term: Antimetabolites - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M8587 - Name: Fluorides - Relevance: LOW - As Found: Unknown - ID: M6182 - Name: Cisplatin - Relevance: HIGH - As Found: Stretching - ID: M21686 - Name: Fluorodeoxyglucose F18 - Relevance: HIGH - As Found: 750 - ID: M7043 - Name: Deoxyglucose - Relevance: HIGH - As Found: Symptom management - ID: M21258 - Name: Radiopharmaceuticals - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003847 - Term: Deoxyglucose - ID: D000002945 - Term: Cisplatin - ID: D000019788 - Term: Fluorodeoxyglucose F18 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01246479 **Brief Title:** Long Term Immunity and Safety Following Vaccination With the JEV IC51 (IXIARO®, JESPECT®) in Pediatric Population In Non Endemic Countries. Uncontrolled, Ph3 FU-Study **Official Title:** Long Term Immunity and Safety Following Vaccination With the Japanese Encephalitis Vaccine IC51(IXIARO®, JESPECT®) In a Pediatric Population in Non Endemic Countries. Uncontrolled, Phase 3 Follow-up Study #### Organization Study ID Info **ID:** IC51-324 #### Organization **Class:** INDUSTRY **Full Name:** Valneva Austria GmbH ### Status Module #### Completion Date **Date:** 2014-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-18 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-10 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-04-29 **Type:** ESTIMATED **Results First Submit Date:** 2015-04-13 **Results First Submit QC Date:** 2015-04-13 #### Start Date **Date:** 2010-10 **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2010-11-23 **Type:** ESTIMATED **Study First Submit Date:** 2010-10-06 **Study First Submit QC Date:** 2010-11-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Valneva Austria GmbH #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study investigates long-term immunity and safety of IC51 (IXIARO®, JESPECT®) in a pediatric population vaccinated in the parent study IC51-322. ### Conditions Module **Conditions:** - Japanese Encephalitis ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 23 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety **Intervention Names:** - Procedure: Blood draw - Biological: IC51 has given in the parent study IC51-322 **Label:** No treatment **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - No treatment **Description:** blood draw at Month 12, Month 24 and Month 36. **Name:** Blood draw **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - No treatment **Description:** No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **Name:** IC51 has given in the parent study IC51-322 **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Rate of subjects with PRNT50 titers of ≥ 1:10 at Month 12 after the first IC51 vaccination (in study IC51-322) **Measure:** Rate of Subjects With PRNT50 Titers of ≥ 1:10 at Month 12 After the First IC51 Vaccination (in Study IC51-322) **Time Frame:** Month 12 #### Secondary Outcomes **Description:** GMT for JEV neutralizing antibodies measured using the PRNT at Month 12, 24 and 36 after the first IC51 vaccination (in study IC51-322) **Measure:** GMT for JEV Neutralizing Antibodies Measured Using the PRNT at Month 12, 24 and 36 After the First IC51 Vaccination (in Study IC51-322) **Time Frame:** Month 12, 24 and 36 **Description:** Rate of subjects with PRNT50 titers of ≥ 1:10 at Months 24 and 36 after the first IC51 vaccination (in study IC51-322) **Measure:** Rate of Subjects With PRNT50 Titers of ≥ 1:10 at Months 24 and 36 After the First IC51 Vaccination (in Study IC51-322) **Time Frame:** Month 24, 36 **Description:** Rate of subjects with SAEs following immunization up to Months 12, 24 and 36 after the first IC51 vaccination (in study IC51-322) **Measure:** Rate of Subjects With SAEs Following Immunization up to Months 12, 24 and 36 After the First IC51 Vaccination (in Study IC51-322) **Time Frame:** Months 12, 24 and 36 **Description:** Rate of subjects with AEs and medically attended AEs up to Months 12, 24 and 36 after the first IC51 vaccination (in study IC51-322). **Measure:** Rate of Subjects With AEs and Medically Attended AEs up to Months 12, 24 and 36 After the First IC51 Vaccination (in Study IC51-322). **Time Frame:** Months 12, 24 and 36 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects who have received two vaccinations in study IC51 322. (2) Subjects who were enrolled as part of the immunogenicity subgroup of study IC51-322. * Male or female healthy subjects aged ≥ 9 months to \< 21 years at the time of enrolment into this study. * Written informed consent by the subject, the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable. Exclusion Criteria: * History of or clinical manifestation of any Flavivirus disease during study IC51-322. * Vaccination against JE virus (JEV) (except with IC51) at any time prior or planned during this study. * Participation in another study with an investigational product during study IC51-322 or IC51-324. * History of or development of any immunodeficiency including post-organtransplantation after inclusion into study IC51-322. * History of or development of an autoimmune disease during study IC51-322. * Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying medications started during study IC51-322 up to first visit of study IC51-324. (For corticosteroids this means prednisone or equivalent at \>= 0.05 mg/kg/day. Topical or inhaled steroids are allowed). * Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). * Illicit drug use and/or a history of drug or alcohol addiction and/or current drug or alcohol addiction. * Inability or unwillingness by the legal representative(s) and/or the subject (where applicable) to provide informed consent/assent and to abide by the requirements of the study. * Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities). **Healthy Volunteers:** True **Maximum Age:** 20 Years **Minimum Age:** 9 Months **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tampa **Country:** United States **State:** Florida **Location 2:** **City:** Brisbane **Country:** Australia **Location 3:** **City:** Melbourne **Country:** Australia **Location 4:** **City:** Berlin **Country:** Germany **Location 5:** **City:** Hamburg **Country:** Germany #### Overall Officials **Official 1:** **Affiliation:** Valneva Austria GmbH **Name:** Andrea Ayad, Dr. **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Taucher C, Barnett ED, Cramer JP, Eder-Lingelbach S, Jelinek T, Kadlecek V, Kiermayr S, Mills DJ, Pandis D, Reiner D, Dubischar KL. Neutralizing antibody persistence in pediatric travelers from non-JE-endemic countries following vaccination with IXIARO(R) Japanese encephalitis vaccine: An uncontrolled, open-label phase 3 follow-up study. Travel Med Infect Dis. 2020 Mar-Apr;34:101616. doi: 10.1016/j.tmaid.2020.101616. Epub 2020 Mar 7. **PMID:** 32156630 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000090862 - Term: Neuroinflammatory Diseases - ID: D000004671 - Term: Encephalitis, Arbovirus - ID: D000018792 - Term: Encephalitis, Viral - ID: D000020805 - Term: Central Nervous System Viral Diseases - ID: D000002494 - Term: Central Nervous System Infections - ID: D000007239 - Term: Infections - ID: D000069544 - Term: Infectious Encephalitis - ID: D000001102 - Term: Arbovirus Infections - ID: D000079426 - Term: Vector Borne Diseases - ID: D000096724 - Term: Mosquito-Borne Diseases - ID: D000014777 - Term: Virus Diseases - ID: D000012327 - Term: RNA Virus Infections - ID: D000018177 - Term: Flavivirus Infections - ID: D000018178 - Term: Flaviviridae Infections ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M7825 - Name: Encephalitis - Relevance: HIGH - As Found: Encephalitis - ID: M7835 - Name: Encephalitis, Japanese - Relevance: HIGH - As Found: Japanese Encephalitis - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M2803 - Name: Neuroinflammatory Diseases - Relevance: LOW - As Found: Unknown - ID: M20851 - Name: Encephalitis, Viral - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M22560 - Name: Central Nervous System Viral Diseases - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M5743 - Name: Central Nervous System Infections - Relevance: LOW - As Found: Unknown - ID: M457 - Name: Infectious Encephalitis - Relevance: LOW - As Found: Unknown - ID: M4412 - Name: Arbovirus Infections - Relevance: LOW - As Found: Unknown - ID: M2054 - Name: Vector Borne Diseases - Relevance: LOW - As Found: Unknown - ID: M3255 - Name: Mosquito-Borne Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M20323 - Name: Flavivirus Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: T3141 - Name: Japanese Encephalitis - Relevance: HIGH - As Found: Japanese Encephalitis ### Condition Browse Module - Meshes - ID: D000004672 - Term: Encephalitis, Japanese - ID: D000004660 - Term: Encephalitis ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown ### Misc Info Module #### Removed Countries - Country: Denmark - Country: Sweden - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** No Treatment **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** EG000 **Other Num Affected:** 8 **Other Num at Risk:** 23 **Serious Number Affected:** 2 **Serious Number At Risk:** 23 **Title:** No Treatment **Frequency Threshold:** 5 #### Other Events **Term:** Otitis media acute **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Pharyngitis streptococcal **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Diarrhoea **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Skin papilloma **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** #### Serious Events **Term:** Staphylococcal infection **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 23 **Num Events:** 1 **Term:** Tonsillitis **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 23 **Num Events:** 1 **Time Frame:** adverse event data were collected up to month 36 (i.e., approximately 3 years after primary immunization in the parent study IC51-322) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 23 **Units:** Participants ### Group **ID:** BG000 **Title:** No Treatment **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 4.3 **Value:** 14.3 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 11 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** GT60 **Restrictive Agreement:** True ### Point of Contact **Email:** info@valneva.com **Organization:** Valneva Austria GmbH **Phone:** +43120620 **Phone Extension:** 0 **Title:** Senior Scientist Clinical Research ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 68.6 - **Spread:** - **Upper Limit:** 97.1 - **Value:** 89.5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 28.7 - **Spread:** - **Upper Limit:** 79.8 - **Value:** 47.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 45.9 - **Spread:** - **Upper Limit:** 123.7 - **Value:** 75.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 19 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 34.8 - **Spread:** - **Upper Limit:** 106.1 - **Value:** 60.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 **Units:** Participants #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 21 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 17 **Units:** Participants #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Rate of subjects with PRNT50 titers of ≥ 1:10 at Month 12 after the first IC51 vaccination (in study IC51-322) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** intention to treat population; assessment of seroprotection \~1 year post primary vaccination series in parent study IC51-322 **Reporting Status:** POSTED **Time Frame:** Month 12 **Title:** Rate of Subjects With PRNT50 Titers of ≥ 1:10 at Month 12 After the First IC51 Vaccination (in Study IC51-322) **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** OG000 **Title:** No Treatment #### Outcome Measure 2 **Description:** GMT for JEV neutralizing antibodies measured using the PRNT at Month 12, 24 and 36 after the first IC51 vaccination (in study IC51-322) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Intent to Treat Population **Reporting Status:** POSTED **Time Frame:** Month 12, 24 and 36 **Title:** GMT for JEV Neutralizing Antibodies Measured Using the PRNT at Month 12, 24 and 36 After the First IC51 Vaccination (in Study IC51-322) **Type:** SECONDARY **Unit of Measure:** Titer ##### Group **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** OG000 **Title:** No Treatment #### Outcome Measure 3 **Description:** Rate of subjects with PRNT50 titers of ≥ 1:10 at Months 24 and 36 after the first IC51 vaccination (in study IC51-322) **Parameter Type:** NUMBER **Population Description:** Intent to Treat Population **Reporting Status:** POSTED **Time Frame:** Month 24, 36 **Title:** Rate of Subjects With PRNT50 Titers of ≥ 1:10 at Months 24 and 36 After the First IC51 Vaccination (in Study IC51-322) **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** OG000 **Title:** No Treatment #### Outcome Measure 4 **Description:** Rate of subjects with SAEs following immunization up to Months 12, 24 and 36 after the first IC51 vaccination (in study IC51-322) **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population **Reporting Status:** POSTED **Time Frame:** Months 12, 24 and 36 **Title:** Rate of Subjects With SAEs Following Immunization up to Months 12, 24 and 36 After the First IC51 Vaccination (in Study IC51-322) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** OG000 **Title:** No Treatment #### Outcome Measure 5 **Description:** Rate of subjects with AEs and medically attended AEs up to Months 12, 24 and 36 after the first IC51 vaccination (in study IC51-322). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Population **Reporting Status:** POSTED **Time Frame:** Months 12, 24 and 36 **Title:** Rate of Subjects With AEs and Medically Attended AEs up to Months 12, 24 and 36 After the First IC51 Vaccination (in Study IC51-322). **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 was given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** OG000 **Title:** No Treatment ### Participant Flow Module #### Group **Description:** subjects will be followed up on immunity (analysis of blood samples) and safety Blood draw: blood draw at Month 12, Month 24 and Month 36. IC51 has given in the parent study IC51-322: No more vaccinations in IC51-324 since this a study for long-term follow-up on safety and immunogenicity after vaccinations in parent study IC51-322. **ID:** FG000 **Title:** No Treatment #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 23 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 18 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 5 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01700179 **Brief Title:** Evaluation of Safety, Tolerability, and Antiviral Activity of ACH-0143102 Plus Ribavirin In Treatment-naive Hepatitis C Virus Infection Genotype 1b Participants **Official Title:** A Phase 1b, Open-label, Pilot Study to Evaluate the Safety, Tolerability, and Antiviral Activity of Oral ACH-0143102 Administered in Combination With Ribavirin for 12 Weeks in Treatment-naive Subjects With Chronic Hepatitis C Virus Infection Genotype 1b #### Organization Study ID Info **ID:** ACH102-005 #### Organization **Class:** INDUSTRY **Full Name:** Alexion Pharmaceuticals, Inc. ### Status Module #### Completion Date **Date:** 2013-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-29 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-10-03 **Type:** ESTIMATED **Results First Submit Date:** 2014-09-30 **Results First Submit QC Date:** 2014-09-30 #### Start Date **Date:** 2012-09 **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2012-10-04 **Type:** ESTIMATED **Study First Submit Date:** 2012-10-02 **Study First Submit QC Date:** 2012-10-02 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Achillion, a wholly owned subsidiary of Alexion #### Lead Sponsor **Class:** INDUSTRY **Name:** Alexion Pharmaceuticals, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study was to evaluate the safety, tolerability, and efficacy of 12 weeks of treatment with ACH-0143102 and ribavirin in genotype 1b (GT1b), treatment-naive, hepatitis C virus (HCV) participants. **Detailed Description:** A Phase 1b, pilot study that evaluated the safety, tolerability, and antiviral activity of oral ACH-0143102 administered in combination with ribavirin for 12 weeks in treatment-naive participants with chronic HCV GT1b. ### Conditions Module **Conditions:** - Chronic Hepatitis C Infection ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** ACH-0143102 loading dose (225 milligrams \[mg\]) on Day 1, followed by maintenance doses (75 mg) on Days 2-84, plus weight-based ribavirin as per label on Days 1-84. **Intervention Names:** - Drug: ACH-0143102 - Drug: Ribavirin **Label:** ACH-0143102 plus ribavirin daily **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - ACH-0143102 plus ribavirin daily **Name:** ACH-0143102 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - ACH-0143102 plus ribavirin daily **Name:** Ribavirin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** To determine the incidence of the SVR12 after the completion of dosing with ACH-0143102 plus ribavirin, reported as hepatitis C virus ribonucleic acid less than the limit of quantification at that time point. **Measure:** Sustained Virologic Response At 12 Weeks (SVR12) **Time Frame:** 12 weeks following the last dose ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Males and females aged 18 years and older. * Clinical diagnosis of hepatitis C with GT1b. * Chronic hepatitis C treatment-naive participants. * Interleukin 28B genotype CC. * HCV ribonucleic acid \> 10,000 international units/milliliter at screening. * Female participants must be willing to use 2 effective methods of contraception during the dosing period and for 6 months after the last dose of ribavirin. * Male participants must be willing to use an effective barrier method of contraception throughout the dosing period and for 6 months after the last dose of ribavirin. Male participants must agree not to donate sperm while enrolled in the study and for 6 months after the last dose of ribavirin. * Willing to participate in all study activities and all study requirements. Exclusion Criteria: * Body mass index \> 36 kilograms/meter squared. * Pregnant or nursing females. * Clinically significant laboratory abnormalities at screening. * Previous participation in a clinical trial with protease inhibitor and/or non-structural protein 5A inhibitor. * Human immunodeficiency virus infection or other liver diseases. * Positive hepatitis B surface antigen. * Liver cirrhosis. * Uncontrolled psychiatric disease. * Clinical evidence of chronic cardiac disease. * History of malignancy of any organ system within 5 years. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000004769 - Term: Enterovirus Infections - ID: D000010850 - Term: Picornaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000086982 - Term: Blood-Borne Infections - ID: D000018178 - Term: Flaviviridae Infections - ID: D000002908 - Term: Chronic Disease ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9607 - Name: Hepatitis, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis - ID: M17522 - Name: Virus Diseases - Relevance: HIGH - As Found: Virus Infection - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M21613 - Name: Hepatitis C, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis C - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M7930 - Name: Enterovirus Infections - Relevance: LOW - As Found: Unknown - ID: M13745 - Name: Picornaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000019698 - Term: Hepatitis C, Chronic - ID: D000014777 - Term: Virus Diseases - ID: D000006505 - Term: Hepatitis - ID: D000006521 - Term: Hepatitis, Chronic ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M15083 - Name: Ribavirin - Relevance: HIGH - As Found: Bevacizumab - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000012254 - Term: Ribavirin ### Misc Info Module #### Removed Countries - Country: United States - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Treatment-emergent adverse events are summarized. #### Event Groups **Group ID:** EG000 **Title:** ACH-0143102 Plus Ribavirin **Description:** ACH-0143102 (225 mg) loading dose on Day 1, followed by maintenance doses (75 mg) on Days 2-84, plus weight-based ribavirin as per label on Days 1-84. **ID:** EG000 **Other Num Affected:** 6 **Other Num at Risk:** 8 **Serious Number At Risk:** 8 **Title:** ACH-0143102 Plus Ribavirin **Frequency Threshold:** 0 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Atrioventricular block second degree **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Eructation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Haematochezia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Oral pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Influenza like illness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Folliculitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 16.0 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 16.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 16.0 **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 16.0 **Term:** Foreign body in eye **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 16.0 **Term:** Muscle strain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 16.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Joint swelling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Emotional disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Breast tenderness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Vulvovaginal pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Sinus congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Upper respiratory tract congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Dry skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Rash macular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 16.0 **Term:** Rash maculo-papular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 16.0 **Time Frame:** Adverse event data were collected from enrollment into the study through end of treatment plus 24 weeks of follow-up, for up to 36 weeks. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 8 **Units:** Participants ### Group **ID:** BG000 **Title:** ACH-0143102 Plus Ribavirin **Description:** ACH-0143102 (225 mg) loading dose on Day 1, followed by maintenance doses (75 mg) on Days 2-84, plus weight-based ribavirin as per label on Days 1-84. ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 8 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 11.34 **Value:** 50.07 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 6 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 6 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 4.183 **Value:** 28.13 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Body Mass Index **Unit of Measure:** kilograms/meter squared **Population Description:** The analysis population for baseline characteristics was all enrolled participants. ## Results Section - More Information Module ### Certain Agreement **Other Details:** Prior to submitting/presenting a manuscript or materials relating to a Study to a publisher, reviewer, or outside person, the Institution shall provide to Sponsor a copy of all such manuscripts or materials, and Sponsor shall have thirty (30) days to review and comment. The Institution shall, upon Sponsor's request, further delay publication or presentation for a period of up to sixty (60) days to allow Sponsor to protect its interests in any Sponsor Inventions. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** clinicaltrials@alexion.com **Organization:** Alexion Pharmaceuticals Inc. **Phone:** 855-752-2356 **Title:** Alexion Pharmaceuticals Inc. ## Results Section - Outcome Measures Module ### Outcome Measure 1 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** To determine the incidence of the SVR12 after the completion of dosing with ACH-0143102 plus ribavirin, reported as hepatitis C virus ribonucleic acid less than the limit of quantification at that time point. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** 12 weeks following the last dose **Title:** Sustained Virologic Response At 12 Weeks (SVR12) **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** ACH-0143102 (225 mg) loading dose on Day 1, followed by maintenance doses (75 mg) on Days 2-84, plus weight-based ribavirin as per label on Days 1-84. **ID:** OG000 **Title:** ACH-0143102 Plus Ribavirin ### Participant Flow Module #### Group **Description:** ACH-0143102 (225 milligrams \[mg\]) loading dose on Day 1, followed by maintenance doses (75 mg) on Days 2-84, plus weight-based ribavirin as per label on Days 1-84. **ID:** FG000 **Title:** ACH-0143102 Plus Ribavirin #### Period **Title:** Overall Study ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 **Pre-Assignment Details:** Participants were screened within 4 weeks (-28 to -1 days) before administration of the study drug. Participants who meet all eligibility criteria were instructed to arrive at the study center on the baseline day. **Recruitment Details:** Participants were recruited from 6 sites in the United States between 05 September 2012 and 11 December, 2012. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02581579 **Brief Title:** Study to Evaluate the Tolerability and Immunogenicity of Nyaditum Resae ® Probiotic Administered to Pediatric Population in Contact With Tuberculosis With or Without Latent Tuberculosis Infection **Official Title:** Pilot Phase I Clinical Trial, Double-blind, Randomized, Placebo Controlled and Masked to Evaluate the Tolerability and Immunogenicity of Nyaditum Resae ® Probiotic Administered to Pediatric Population in Contact With Tuberculosis With or Without Latent Tuberculosis Infection #### Organization Study ID Info **ID:** NYADAPETRICS #### Organization **Class:** INDUSTRY **Full Name:** Manresana de Micobacteriologia, SL ### Status Module #### Completion Date **Date:** 2019-03-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-12-04 **Type:** ACTUAL **Last Update Submit Date:** 2019-12-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-03-06 **Type:** ACTUAL #### Start Date **Date:** 2015-12-09 **Type:** ACTUAL **Status Verified Date:** 2019-12 #### Study First Post Date **Date:** 2015-10-21 **Type:** ESTIMATED **Study First Submit Date:** 2015-10-19 **Study First Submit QC Date:** 2015-10-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Manresana de Micobacteriologia, SL #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a doble-blind, masked, compared with placebo clinical trial in pediatric population in contact with tuberculosis with or without tuberculosis infection. This trial aims to study the effect of the probiotic Nyaditum resae® at the level of specific Treg memory cells eight weeks after the first administration, and the global tolerability of the treatment. Nyaditum resae® is a preparation in the form of capsules containing heat-killed environmental mycobacteria Mycobacterium manresensis. The overall objective of the study is the effect of Nyaditum resae® on immunity, which could reduce the risk of developing active tuberculosis. **Detailed Description:** The incidence of tuberculosis is still a problem of the first magnitude. Every year 1.5 million people die; there are 10 million cases of illness and 100 million new infected. The growing problem of multi-resistance is to be added, remaining so prevalent: 700,000 patients, a figure that increases annually with 100,000 people. Prevention of tuberculosis is currently very difficult because it is a disease caused by a bacillus (Mycobacterium tuberculosis) that is transmitted by air: No risk factor for becoming infected has been identified and there is still no prophylactic vaccine that prevents from infection. One of the most characteristic aspects of tuberculosis is that the majority (90-95 %) of people without immunity alterations do not develop the disease after being infected. As for people who do develop the disease, it is still not known why they develop it. A group of researchers from the Institut Germans Trias i Pujol recently discovered a mechanism that explains this trend. In short, what happens is that certain people create a too strong inflammatory response against tuberculosis bacillus, which ends up creating massive destruction of the tissue that is around the bacillus and brings the characteristic lesion of tuberculosis: tuberculous cavity. This group of researchers was devising ways to "reeducate" the immune system against the bacillus not make it aggressive. And they did it using two instruments. The first one, an environmental mycobacteria, namely a bacillus of the family of mycobacteria tuberculosis, that usually lives in the water we drink, so that at a greater or lesser extent we already have it in our intestinal flora. The second, inducing a tolerant response, like we do when we eat food. To induce a tolerant response, low and repeated doses of the product make the immune system of the digestive duct "used to" their presence. Thus, when it becomes to find the product, the immune system reacts in a very light and balanced manner, avoiding excessive inflammatory responses. The clearest example is the fact that our immune system "is used" to feed proteins and generates no rejection answers found in the intestinal mucosa. Hence comes the probiotic Nyaditum resae®, a preparation in the form of capsules, containing a heat-killed Mycobacterium manresensis and thus can generate a cross-immunity with the tuberculosis bacillus. By giving low and repeated dose to generate a tolerant response, which happens when there is an infection by Mycobacterium tuberculosis, so that a balanced immune response is triggered able to reduce the risk of developing active tuberculosis. Tolerability of Nyaditum resae® has been studied in adults. Next step is to asses its behavior in pediatric population, since is a particularly vulnerable population in countries where there is a high incidence of this disease. ### Conditions Module **Conditions:** - Tuberculosis **Keywords:** - Tuberculosis - Tregs - Tolerance - Probiotic - Mycobacteria ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 24 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis **Intervention Names:** - Dietary Supplement: Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis **Label:** Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** MANITOL CAPSULES **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis **Description:** Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis, 1 capsule per day during 14 **Name:** Nyaditum resae ® 10e5 of heat-killed Mycobacterium manresensis **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo, 1 capsule per day during 14 **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Change from Baseline in Specific Treg memory cells at week 1 **Time Frame:** From Baseline to Week 8 **Measure:** Proportion of patients presenting adverse events related to study treatment. **Time Frame:** From Baseline to Week 8 #### Secondary Outcomes **Measure:** Proportion of participants presenting gastrointestinal adverse events related to study treatment. **Time Frame:** Baseline to week 8 **Measure:** Proportion of participants presenting systemic adverse events related to study treatment. **Time Frame:** Baseline to week 8 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Child from a study of contact with tuberculosis. Obtaining informed consent from parents / mothers or guardians and, over 12 years, obtaining the consent of the child. Child between 2 and 17 years (inclusive) on the day of obtaining informed consent. Willingness to fulfill the requirements of the protocol. Exclusion Criteria: Active tuberculosis. Enrollment in another clinical trial or study with sanitary product involving invasive techniques. Chronic administration of: methotrexate, azathioprine, cyclophosphamide, oral corticosteroids (≥500mg cumulative prednisone dose, or equivalent; inhaled or topical steroids are allowed) and other immunosuppressive therapies / immunomodulatory . Administration of blood products or blood derivatives during the 6 months prior to randomization. Vaccination in the month prior to randomization. Anticipation of receiving vaccines duration of the study. Detection by the researcher lack of knowledge or willingness to participate and fulfill all the requirements of the protocol. Any other finding that the investigator's opinion, could jeopardize the performance of the protocol or significantly influence the results or interpretation of the effects of probiotic. Known immunodeficiencies. Pregnancy or breastfeeding. Hypersensitivity to mannitol **Healthy Volunteers:** True **Maximum Age:** 17 Years **Minimum Age:** 2 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Badalona **Country:** Spain **Facility:** Germans Trias I Pujol Hospital **State:** Barcelona **Zip:** 08916 **Location 2:** **City:** Esplugues de Llobregat **Country:** Spain **Facility:** Hospital Sant Joan de Déu **State:** Barcelona **Zip:** 08950 **Location 3:** **City:** Barcelona **Country:** Spain **Facility:** Valle Hebron Hospital **Zip:** 08035 ### References Module #### References **Citation:** Tukvadze N, Cardona P, Vashakidze S, Shubladze N, Avaliani Z, Vilaplana C, Cardona PJ. Development of the food supplement Nyaditum resae as a new tool to reduce the risk of tuberculosis development. Int J Mycobacteriol. 2016 Dec;5 Suppl 1(Suppl 1):S101-S102. doi: 10.1016/j.ijmyco.2016.09.073. Epub 2016 Nov 14. **PMID:** 28043488 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007239 - Term: Infections - ID: D000009164 - Term: Mycobacterium Infections - ID: D000000193 - Term: Actinomycetales Infections - ID: D000016908 - Term: Gram-Positive Bacterial Infections - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000085343 - Term: Latent Infection ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M12119 - Name: Mycobacterium Infections - Relevance: LOW - As Found: Unknown - ID: M17127 - Name: Tuberculosis - Relevance: HIGH - As Found: Tuberculosis - ID: M28410 - Name: Latent Tuberculosis - Relevance: HIGH - As Found: Latent Tuberculosis - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M19252 - Name: Gram-Positive Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: M2512 - Name: Latent Infection - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014376 - Term: Tuberculosis - ID: D000055985 - Term: Latent Tuberculosis ### Intervention Browse Module - Browse Branches - Abbrev: NaAg - Name: Natriuretic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11342 - Name: Mannitol - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06278779 **Acronym:** TREK **Brief Title:** Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression **Official Title:** Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-Resistant Depression: a Randomised, Rater-blinded Trial #### Organization Study ID Info **ID:** X23-0311 #### Organization **Class:** OTHER **Full Name:** The George Institute ### Status Module #### Completion Date **Date:** 2027-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-06 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-03 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2027-04 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-02-26 **Type:** ACTUAL **Study First Submit Date:** 2024-01-20 **Study First Submit QC Date:** 2024-02-19 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** The University of New South Wales #### Lead Sponsor **Class:** OTHER **Name:** The George Institute #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this study is to compare the effectiveness of two formulations of ketamine - Spravato® and racemic ketamine - in people with treatment-resistant depression (TRD). The main questions it aims to answer are: * How the two formulations compare in terms of their effectiveness in treating TRD. * How the two formulations compare in their acceptability to patients, safety, effects on patient quality of life and function, and cost effectiveness. Participants will be randomised to receive either Spravato® or racemic ketamine treatment and asked to complete some questionnaires to assess the effects on mood, treatment acceptability, side effects, quality of life and function, and health economic outcomes. **Detailed Description:** The TREK study is a randomized, prospective, rater blinded (primary outcome raters), parallel group, comparative effectiveness trial of racemic ketamine and Spravato®, comparing their effectiveness, acceptability, safety, effects on quality of life (QOL), function and cost effectiveness after 4 weeks - 6 months of treatment in people with TRD. Participants will be recruited from clinics/hospitals that are providing racemic ketamine and Spravato® treatment services for TRD. Participants will be referred, treated and followed up as per the clinic's normal clinical practice. Participants who consent to participate in this research study will undergo other processes in addition to the standard treatment procedures provided by their clinic: * Randomisation to receive racemic ketamine or Spravato®. * Completion of questionnaires to measure treatment effects on mood, acceptability, safety, quality of life and function and cost effectiveness. ### Conditions Module **Conditions:** - Treatment Resistant Depression ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomized, prospective, parallel group, comparative effectiveness trial. ##### Masking Info **Masking:** SINGLE **Masking Description:** Primary outcome raters will be blinded to treatment allocation. **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 162 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dosing of esketamine intranasal spray will be guided by the Spravato® Product Information. This involves a starting dosage of 28 or 56 mg, with dose adjustment up to 84 mg as required to optimise response. Dose adjustments will be based on effectiveness and tolerability to the previous dose. The recommended treatment protocol is twice per week for 4 weeks, then weekly in weeks 5-8, then option of weekly-fortnightly "maintenance" treatment for responders. After week 8, patients may continue treatment as guided by the ketamine clinic psychiatrist. **Intervention Names:** - Drug: Esketamine group **Label:** Esketamine group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Treatment administration will follow standard clinical practice in the recruiting clinic, with a recommendation to follow an evidence-based and established dose-optimising approach, given by injection, twice per week for 4 weeks, then the frequency of further treatments (week 5 - month 6) will be based on the clinical judgement of the ketamine clinic psychiatrist. Dosing will be adjusted by the ketamine clinic psychiatrist, based on clinical response, safety and tolerability. The psychiatrist will review the patient before each treatment, over the first 4 weeks, to judge the dose level required. Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted using an ascending dose titration schedule if the patient has not shown clinical response and if side effects are adequately tolerated. . **Intervention Names:** - Drug: Racemic ketamine **Label:** Racemic ketamine **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Esketamine group **Description:** The recommended dosing for Spravato is: Weeks 1-4: Starting Day 1 dose: \< 65 years: 56 mg ≥ 65 years: 28 mg Subsequent doses: 28 mg (≥ 65 years), 56 mg or 84 mg twice weekly Weeks 5-8: 28 mg (≥ 65 years), 56 mg or 84 mg once weekly From Week 9: 28 mg (≥ 65 years), 56 mg or 84 mg every 2 weeks or once weekly **Name:** Esketamine group **Other Names:** - Spravato® **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Racemic ketamine **Description:** Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted as needed using an ascending dose titration schedule: 1. 0.5 mg/kg 2. 0.6 mg/kg 3. 0.75 mg/kg 4. 0.9 mg/kg 5. Further increments by 0.1-0.2 mg/kg, up to max 1.5 mg/kg **Name:** Racemic ketamine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Change in score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. MADRS includes questions on ten symptoms, each of which yields a score of 0 to 6. The total score ranges from 0 to 60. The higher the MADRS score the more severe the depression. Cutoff points are for levels of depression are: 0 to 6: normal /symptom absent 7 to 19: mild depression 20 to 34: moderate depression 35 to 60: severe depression. **Measure:** Montgomery-Asberg Depression Rating Scale (MADRS) **Time Frame:** From week 0 to week 4. #### Secondary Outcomes **Description:** Score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. See outcome 1 for minimum and maximum values, and whether higher scores indicate a better or worse outcome. **Measure:** Montgomery-Asberg Depression Rating Scale (MADRS) score **Time Frame:** At week 8 and month 6 **Description:** Response (≥50% improvement in MADRS) **Measure:** Response - Montgomery-Asberg Depression Rating Scale (MADRS) **Time Frame:** Weeks 4, 8 and month 6 **Description:** Remission (MADRS score ≤10) **Measure:** Remission - Montgomery-Asberg Depression Rating Scale (MADRS) **Time Frame:** Weeks 4, 8 and month 6 **Description:** Depression, Anxiety and Stress Scale (DASS-21) - will be used to measure psychological distress. It consists of three 7-item subscales, with items scored on a 4-point Likert scale (0-3) and summed to obtain subscale scores. **Measure:** DASS-21 **Time Frame:** Performed weekly from baseline to week 8 inclusive and at 6 month visit. **Description:** The Clinical Global Impression - Improvement scale (CGI-I) is used to assess depressive symptom improvement from study baseline. The minimum value is -6 (maximum deterioration) and the maximum value is 6 (ideal improvement). **Measure:** Clinical Global Impression-Improvement (CGI-I) **Time Frame:** Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits. **Description:** The Clinical Global Impression - Severity scale (CGI-S) is used to assess depressive symptom severity. The minimum value is 1 (normal) and the maximum value is 7 (among the most extremely ill patients). **Measure:** Clinical Global Impression-Severity (CGI-S) **Time Frame:** Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits. **Description:** Columbia Suicide Severity Rating Scale (C-SSRS) - short questionnaire that will be used by the clinic teams as a clinical tool to assess suicidality. **Measure:** Columbia Suicide Severity Rating Scale (C-SSRS) **Time Frame:** Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits. **Description:** Speed of response, assessed by number of treatments required to attain CGI-I score of ≥ 3. **Measure:** Speed of response - Clinical Global Impression-Improvement (CGI-I) **Time Frame:** Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits. **Description:** Assessed via the Ketamine Side Effect Tool (KSET), designed to monitor the acute, cumulative and longer-term safety of ketamine treatment. **Measure:** Psychotomimetic symptoms **Time Frame:** Through study completion at each treatment visit, up to 6 months **Description:** Data collected as an Adverse Event of Special Interest **Measure:** Suicide attempts or gestures **Time Frame:** During 6-month study period **Description:** Bladder Pain-Interstitial Cystitis Symptom Score (BPIC-SS) - a self-report symptom-based instrument that identifies moderate to severe bladder pain syndrome. Side effects of racemic ketamine/Spravato® include inflammation of the bladder endothelium. From 8 questions about bladder/urination pain, patients can score a minimum of 0 (asymptomatic) and a maximum of 38 (severe symptoms). **Measure:** Number of Participants with urinary symptoms, as assessed using the Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) **Time Frame:** Performed at baseline, week 4, week 8 and at 6 month visit. **Description:** Cognitive Failures Questionnaire (CFQ) is a self-rated tool to assess subjective impression of cognitive functioning. From 25 questions, patients can score a minimum of 0 (best) and a maximum of 100 (worst). **Measure:** Cognitive Failure Questionnaire scores (CFQ) **Time Frame:** Performed at baseline, week 4, week 8 and at 6 month visit. **Description:** Ketamine liking/craving score will be used as a measure of ketamine craving/abuse. A visual analogue scale is used, where patients can score a minimum of 0 (strong dislike/no craving) and a maximum of 30 (very strong liking/constant craving). **Measure:** Ketamine liking/craving score **Time Frame:** Performed at baseline, week 4, week 8 and at 6 month visit. **Description:** Assessed via the Ketamine Side Effect Tool (KSET), designed to monitor the acute, cumulative and longer-term safety of ketamine treatment. **Measure:** Number of Participants with urinary symptoms, as assessed using the Ketamine Side Effect Tool (KSET) **Time Frame:** Through study completion at each treatment visit, up to 6 months **Description:** An 8-item self-rated instrument to assess the acceptability of healthcare interventions. This evaluates the constructs of affective attitude, effort burden, ethicality, perceived effectiveness, intervention coherence, self-efficacy, opportunity costs and general acceptability. Patients can score a minimum of 8 (very unacceptable) and a maximum of 40(very acceptable). "If reporting a score on a scale, please include the minimum and maximum values, and whether higher scores mean a better or worse outcome." Appears that not all high scores are positive so makes it hard to address this issue. **Measure:** Acceptability Questionnaire **Time Frame:** Performed at week 4, week 8 and at 6 month visit. **Description:** Collected via case report form. Captures reason for ceasing, switching or re-starting study medication. **Measure:** End of Treatment questionnaire **Time Frame:** Used at end of the treatment period(s) over the course of the study. **Description:** Recovering Quality of Life, 10-item (REQOL-10) is used to assess the quality of life for people with different mental health conditions. Patients can score a minimum of 0 (poorest quality of life) and a maximum of 40 (highest quality of life). **Measure:** Recovering Quality of Life Questionnaire (REQOL-10) **Time Frame:** Over 6 month study period **Description:** 12-item WHO Disability Assessment Scale (WHODAS-12) is a 12-item self-rated assessment of health and disability. It will be used to assess functionality. Patients can score a minimum of 0 (no disability) and a maximum of 48 (complete disability). **Measure:** WHO Disability Assessment Scale (WHODAS-12) **Time Frame:** Over 6 month study period **Description:** Patient Health Questionnaire-9 (PHQ-9) is a self-report screening tool designed to assess the severity of depressive symptoms in individuals and monitors symptom changes and treatment effects over time. Patients can score a minimum of 0 (no depression) and a maximum of 27 (severe depression). **Measure:** Patient Health Questionnaire-9 (PHQ-9) **Time Frame:** Over 6 month study period **Description:** Assessment of Quality of Life Questionnaire (AQoL-8D) consists of 35 items covering 8 dimensions: Independent Living, Pain, Senses, Mental Health, Happiness, Coping, Relationships, and Self-worth. It will be used to assess quality of life outcomes and to facilitate the health economics analysis. There is a max patient score of 1 (perfect health) and a minimum score of 0 (deceased) based on weighted utility scores **Measure:** Assessment of Quality of Life Questionnaire (AQoL-8D) **Time Frame:** Over 6 month study period **Description:** The resource use questionnaire (RUQ) collects information regarding the type and number of contacts with the health system including hospitalisations, consultations and medications. The information is then 'scored' by multiplying indicative unit costs by the number of contacts for each service used. The costs per service are summed to calculate a total health sector cost. The resource use questionnaire also collects information regarding time missed (absenteeism) and time working at reduced capacity (presenteeism) for paid work and time missed from unpaid work. The number of hours missed and working at reduced capacity from paid work will be valued using an average wage rate. The hours missed from unpaid work will be valued using a shadow cost for the value of leisure time. These costs are summed and combined with health sector costs to calculate societal costs. **Measure:** Resource Use Questionnaire (RUQ) **Time Frame:** Over 6 month study period **Description:** The Treatment Preferences questionnaire is a simple 3 item self-report questionnaire which asks participants to indicate their treatment preference for one of the 2 interventions, if any; their strength of preference (slight, moderate or strong); their reason for preference (Prefer this method of receiving the medication; Had this treatment before and benefitted; Past negative experience with the other treatment; Impression from reports, other people or media; Other (please specify)) **Measure:** Treatment Preference **Time Frame:** Assessed once, prior to randomization **Description:** The SETS is a self-report questionnaire that assesses positive and negative treatment expectations with 6 items rated on a 7-point Likert scale from 0 'not agree at all' to 6 'fully agree'; additional questions ask the responder to confirm the treatment they will receive and whether they have received it before as well as whether any specific benefits or harms/negative side effects are expected **Measure:** Stanford Expectations of Treatment Scale (SETS) **Time Frame:** Assessed once, after randomization and before first treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult with treatment-resistant depression (TRD: not responded adequately to at least two different antidepressants of adequate dose and duration) who has a current depressive episode (DSM 5) * Assessed and attested by clinic psychiatrist as appropriate to receive either racemic ketamine or Spravato® ketamine treatment for TRD * Aged ≥18 years * Written informed consent for research study obtained Exclusion Criteria: * Not able to give informed consent * Any physical or mental condition which, in the opinion of the investigator, could interfere with study participation including outcome assessments * Patients who require an interpreter/translator for the clinic consent process, due to the infeasibility of obtaining an interpreter for research assessments, including self-rated scales **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** sjacoby@georgeinstitute.org.au **Name:** Simone Jacoby **Phone:** 80524300 **Role:** CONTACT **Contact 2:** **Email:** ayaourtis@georgeinstitute.org.au **Name:** Andria Yaourtis **Phone:** 80524300 **Role:** CONTACT #### Locations **Location 1:** **City:** Camperdown **Contacts:** ***Contact 1:*** - **Email:** SLHD-RPA-KetamineClinic@health.nsw.gov.au - **Name:** Hadley Lindsay - **Role:** CONTACT ***Contact 2:*** - **Name:** Nicholas Glozier - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** Royal Prince Alfred Hospital **State:** New South Wales **Zip:** 2050 **Location 2:** **City:** Randwick **Contacts:** ***Contact 1:*** - **Email:** depressionclinic@blackdog.org.au - **Name:** Stella Antoniou - **Role:** CONTACT ***Contact 2:*** - **Name:** Adam Bayes - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** Black Dog Institute **State:** New South Wales **Zip:** 2031 **Location 3:** **City:** St Leonards **Contacts:** ***Contact 1:*** - **Email:** neuroinfo.nsc@ramsayhealth.com.au - **Name:** Mayra Ouriques - **Role:** CONTACT ***Contact 2:*** - **Name:** Colleen Loo - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** Ramsay Clinic Northside **State:** New South Wales **Zip:** 2065 **Location 4:** **City:** Warners Bay **Contacts:** ***Contact 1:*** - **Email:** ClinicalTrialsUnit.WBP@ramsayhealth.com.au - **Name:** Sally Sally Wilkinson - **Role:** CONTACT ***Contact 2:*** - **Email:** ClinicalTrialsUnit.WBP@ramsayhealth.com.au - **Name:** Natasha Cairns - **Role:** CONTACT ***Contact 3:*** - **Name:** Michael Bull - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** Ramsay Clinic Lakeside **State:** New South Wales **Zip:** 2282 **Location 5:** **City:** Southport **Contacts:** ***Contact 1:*** - **Email:** specialistmooddisorderclinic@health.qld.gov.au - **Name:** Catherine Donald - **Role:** CONTACT ***Contact 2:*** - **Name:** Shanthi Sarma - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** Gold Coast University Hospital **State:** Queensland **Zip:** 4215 **Location 6:** **City:** Melbourne **Contacts:** ***Contact 1:*** - **Email:** research.arc@ramsayhealth.com.au - **Name:** Melanie Hurley - **Role:** CONTACT ***Contact 2:*** - **Name:** Malcolm Hopwood - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** Ramsay Clinic Albert Road **State:** Victoria **Zip:** 3004 #### Overall Officials **Official 1:** **Affiliation:** The University of New South Wales **Name:** Colleen Loo **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depression - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depression - ID: M29783 - Name: Depressive Disorder, Treatment-Resistant - Relevance: HIGH - As Found: Treatment Resistant Depression - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder - ID: D000061218 - Term: Depressive Disorder, Treatment-Resistant ### Intervention Browse Module - Ancestors - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000778 - Term: Anesthetics, Dissociative - ID: D000018686 - Term: Anesthetics, Intravenous - ID: D000018681 - Term: Anesthetics, General - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000018691 - Term: Excitatory Amino Acid Antagonists - ID: D000018683 - Term: Excitatory Amino Acid Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000928 - Term: Antidepressive Agents - ID: D000011619 - Term: Psychotropic Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Analg - Name: Analgesics - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PsychDr - Name: Psychotropic Drugs ### Intervention Browse Module - Browse Leaves - ID: M10674 - Name: Ketamine - Relevance: HIGH - As Found: Provided - ID: M271980 - Name: Esketamine - Relevance: HIGH - As Found: Auditory - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4108 - Name: Anesthetics, Dissociative - Relevance: LOW - As Found: Unknown - ID: M20766 - Name: Anesthetics, Intravenous - Relevance: LOW - As Found: Unknown - ID: M20761 - Name: Anesthetics, General - Relevance: LOW - As Found: Unknown - ID: M20771 - Name: Excitatory Amino Acid Antagonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M4247 - Name: Antidepressive Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007649 - Term: Ketamine - ID: C000629870 - Term: Esketamine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01640379 **Acronym:** TECH-N **Brief Title:** Technology Enhanced Community Health Nursing (TECH-N) Study **Official Title:** Technology Enhanced Community Health Nursing (TECH-N) to Prevent Recurrent Sexually Transmitted Infections After Pelvic Inflammatory Disease #### Organization Study ID Info **ID:** NA_00068846 #### Organization **Class:** OTHER **Full Name:** Johns Hopkins University #### Secondary ID Infos **ID:** 1R01NR013507-01 **Link:** https://reporter.nih.gov/quickSearch/1R01NR013507-01 **Type:** NIH ### Status Module #### Completion Date **Date:** 2017-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-06-01 **Type:** ACTUAL **Last Update Submit Date:** 2020-05-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2018-05-07 **Type:** ACTUAL **Results First Submit Date:** 2017-12-18 **Results First Submit QC Date:** 2018-04-06 #### Start Date **Date:** 2012-07 **Status Verified Date:** 2020-05 #### Study First Post Date **Date:** 2012-07-13 **Type:** ESTIMATED **Study First Submit Date:** 2012-07-11 **Study First Submit QC Date:** 2012-07-11 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Nursing Research (NINR) #### Lead Sponsor **Class:** OTHER **Name:** Johns Hopkins University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The investigators are enrolling 350 young women 13-25 years old diagnosed with pelvic inflammatory disease (PID) in Baltimore and randomize them to receive community health nurse (CHN) clinical support using a single post-PID face-to-face clinical evaluation and short messaging system communication support during the 30. The investigators hypothesize that repackaging the recommended Centers for Disease Control and Prevention (CDC) follow-up visit using a technology-enhanced community health nursing intervention (TECH-N) with integration of an evidence-based sexually transmitted infection (STI) prevention curriculum will reduce rates of short-term repeat infection by improving adherence to PID treatment and reducing unprotected intercourse and be more cost-effective compared with outpatient standard of care (and hospitalization). **Detailed Description:** Pelvic Inflammatory Disease (PID) remains a serious reproductive health disorder and disease rates remain unacceptably high among minority adolescent girls and young adult women. Each episode of this upper reproductive tract infection, usually caused by a sexually transmitted infection (STI), increases the risk for multiple sequelae including tubal infertility, ectopic pregnancy, and chronic pelvic pain (CPP). Previous research demonstrates that inpatient treatment for PID is expensive without incremental increases in effectiveness when compared with outpatient treatment. The investigators' work and that of others suggest that additional outpatient cost-effective PID health care supports are needed for this vulnerable population to improve short and long-term reproductive health outcomes, including recurrent sexually transmitted infection and PID. Prior research has also demonstrated that community health nurse (CHN) interventions can increase access to appropriate resources enhance health care utilization and promote risk-reducing behavior. The investigators propose that integrating a technology component conducted by the CHN will increase appeal to adolescent females. The investigators' pilot data of a text messaging intervention for reproductive health clinical reminders has demonstrated that use of cell phones to assist urban adolescents residing in high STI prevalent communities with self-care is both highly acceptable and feasible. The investigators hypothesize that repackaging the recommended CDC-follow-up visit using a technology-enhanced community health nursing intervention (TECH-N) with integration of an evidence-based STI prevention curriculum will reduce rates of short-term repeat infection by improving adherence to PID treatment and reducing unprotected intercourse and be more cost-effective compared with outpatient standard of care (and hospitalization). We are enrolling 350 young women 13-21years old diagnosed with PID in Baltimore and randomizing them to receive CHN clinical support using a single post-PID face-to-face clinical evaluation and SMS communication support during the 30-days following the PID diagnosis or optimized standard of care. ### Conditions Module **Conditions:** - Pelvic Inflammatory Disease (PID) **Keywords:** - Pelvic Inflammatory Disease (PID) - Community Health Nursing - Text Messaging - mobile health (mhealth) - Adolescents ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 286 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants receive the Technology Enhanced Community Health Nursing Visit (CHN) within 5 days during which Sister to Sister and clinical assessment performed and text-messaging support **Intervention Names:** - Behavioral: Technology Enhanced Community Health Nursing **Label:** TECH-N **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants receive enhanced standard of care **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - TECH-N **Description:** * Text-messaging (twice daily medication reminders w/ positive adherence messages, positive sexual health messages throughout the 30 day treatment period) * Enhanced community health nursing visit on day 3-5, includes evidence-based STI/HIV prevention component (Sister to Sister Teen) **Name:** Technology Enhanced Community Health Nursing **Other Names:** - Sister to Sister Teen - Short Messaging System (SMS) communication (Text Messages) **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** STI testing (positive Neisseria gonorrhoeae (GC) or Chlamydia trachomatis CT) tested at 90 days using nucleic acid amplification testing (NAAT). **Measure:** Number of Participants With Positive Sexually Transmitted Infection Test (STI) **Time Frame:** 90 Days #### Secondary Outcomes **Description:** Completion of 72-hour assessment visit by medical provider, medication adherence (self-reported), partner notification, partner treatment, and temporary sexual abstinence **Measure:** Number of Participants That Adhered to Self-treatment **Time Frame:** Day 15 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Mild-moderate PID * Outpatient treatment disposition * Permanently reside in the Baltimore Metropolitan area * Willing to sign informed consent \& be randomized Exclusion Criteria: * Pregnant * Concurrent diagnosis of Sexual Assault * Unable to communicate/complete study procedures **Maximum Age:** 25 Years **Minimum Age:** 13 Years **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Baltimore **Country:** United States **Facility:** Johns Hopkins School of Medicine **State:** Maryland **Zip:** 21287 #### Overall Officials **Official 1:** **Affiliation:** Johns Hopkins School of Medicine **Name:** Maria Trent, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Trent M, Yusuf HE, Perin J, Anders J, Chung SE, Tabacco-Saeed L, Rowell J, Huettner S, Rothman R, Butz A, Gaydos CA. Clearance of Mycoplasma genitalium and Trichomonas vaginalis Among Adolescents and Young Adults With Pelvic Inflammatory Disease: Results From the Tech-N Study. Sex Transm Dis. 2020 Nov;47(11):e47-e50. doi: 10.1097/OLQ.0000000000001221. **PMID:** 32569258 **Citation:** Trent M, Perin J, Gaydos CA, Anders J, Chung SE, Tabacco Saeed L, Rowell J, Huettner S, Rothman R, Butz A. Efficacy of a Technology-Enhanced Community Health Nursing Intervention vs Standard of Care for Female Adolescents and Young Adults With Pelvic Inflammatory Disease: A Randomized Clinical Trial. JAMA Netw Open. 2019 Aug 2;2(8):e198652. doi: 10.1001/jamanetworkopen.2019.8652. **PMID:** 31390037 **Citation:** Ha MM, Belcher HME, Butz AM, Perin J, Matson PA, Trent M. Partner Notification, Treatment, and Subsequent Condom Use After Pelvic Inflammatory Disease: Implications for Dyadic Intervention With Urban Youth. Clin Pediatr (Phila). 2019 Oct;58(11-12):1271-1276. doi: 10.1177/0009922819852979. Epub 2019 Jun 5. **PMID:** 31165630 ## Document Section ### Large Document Module #### Large Docs - Date: 2017-05-01 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 425383 - Type Abbrev: Prot_SAP - Upload Date: 2018-04-06T11:45 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007239 - Term: Infections - ID: D000000291 - Term: Adnexal Diseases - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: LOW - As Found: Unknown - ID: M3644 - Name: Pelvic Inflammatory Disease - Relevance: HIGH - As Found: Pelvic Inflammatory Disease - ID: M24398 - Name: Pelvic Infection - Relevance: HIGH - As Found: Pelvic Inflammatory Disease - ID: M3643 - Name: Adnexal Diseases - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000292 - Term: Pelvic Inflammatory Disease - ID: D000034161 - Term: Pelvic Infection ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Intervention **Deaths Num At Risk:** 149 **Description:** Experimental: TECH-N Participants receive the Technology Enhanced Community Health Nursing Visit (community health nursing visits within 5 days during which Sister to Sister and clinical assessment performed and text-messaging support **ID:** EG000 **Other Num Affected:** 1 **Other Num at Risk:** 149 **Serious Number At Risk:** 149 **Title:** Intervention **Group ID:** EG001 **Title:** Control **Deaths Num At Risk:** 137 **Description:** Participants receive enhanced standard of care **ID:** EG001 **Other Num at Risk:** 137 **Serious Number At Risk:** 137 **Title:** Control **Frequency Threshold:** 0 #### Other Events **Term:** Miscarriage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Enrolled participant diagnosed with pregnancy after enrollment, and positive for sexually transmitted infection. The patient could not be reached after multiple attempts and certified letters sent to patient and primary care provider (PCP). **Organ System:** Pregnancy, puerperium and perinatal conditions **Source Vocabulary:** **Time Frame:** Women were followed for adverse events for the primary study period of three months. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 149 **Group ID:** BG001 **Value:** 137 **Group ID:** BG002 **Value:** 286 **Units:** Participants ### Group **ID:** BG000 **Title:** Intervention **Description:** Experimental: TECH-N Participants receive the Technology Enhanced Community Health Nursing Visit (community health nursing visits within 5 days during which Sister to Sister and clinical assessment performed and text-messaging support ### Group **ID:** BG001 **Title:** Control **Description:** Participants receive enhanced standard of care ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 2.4 **Value:** 18.6 #### Measurement **Group ID:** BG001 **Spread:** 2.4 **Value:** 18.8 #### Measurement **Group ID:** BG002 **Spread:** 2.4 **Value:** 18.7 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 149 **Group ID:** BG001 **Value:** 137 **Group ID:** BG002 **Value:** 286 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 149 #### Measurement **Group ID:** BG001 **Value:** 137 #### Measurement **Group ID:** BG002 **Value:** 286 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 149 **Group ID:** BG001 **Value:** 137 **Group ID:** BG002 **Value:** 286 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 136 #### Measurement **Group ID:** BG001 **Value:** 126 #### Measurement **Group ID:** BG002 **Value:** 262 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 12 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 149 **Group ID:** BG001 **Value:** 137 **Group ID:** BG002 **Value:** 286 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 149 #### Measurement **Group ID:** BG001 **Value:** 137 #### Measurement **Group ID:** BG002 **Value:** 286 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 149 **Group ID:** BG001 **Value:** 137 **Group ID:** BG002 **Value:** 286 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Value:** 16 #### Measurement **Group ID:** BG001 **Value:** 9 #### Measurement **Group ID:** BG002 **Value:** 25 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 142 **Group ID:** BG001 **Value:** 127 **Group ID:** BG002 **Value:** 269 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 5 **Description:** Positive sexually transmitted infection test for gonorrhea (GC) or chlamydia (CT) **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Some baseline tests are inconclusive because the sample was not usable, so only 269 out of 286 have results. **Title:** Positive Sexually Transmitted Infection Test (GC or CT) **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** mtrent2@jhmi.edu **Organization:** Johns Hopkins University **Phone:** 4109552910 **Title:** Dr. Maria Trent ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** The odds ratio is for the difference in chlamydia or gonorrhea (CT/GC) rates between arms at ninety days after intervention. **Group Description:** A comparison of Chlamydia or Gonorrhea positivity at 90 days post intervention. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.070 **P-Value Comment:** Judged by type one error limit alpha = 0.05. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.40 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.39 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.98 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** The odds ratio is for the difference in rate of change over time between arms, so is the difference in the odds increment for those receiving TECH N intervention versus the control group. **Group Description:** We used generalized estimating equations to test for a difference in the trend of chlamydia or gonorrhea (CT/GC) rates over the study period. The null hypothesis is that rates of CT/GC for women in the intervention arm were changing over the study period similarly to CT/GC rates in the control arm. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.043 **P-Value Comment:** Judged by type one error limit alpha = 0.05. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.59 **Statistical Comment:** **Statistical Method:** generalized estimating equations **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 37.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 230.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is interpretable as the expected chance of having a 72 follow-up for intervention women compared to women in the control arm, given similar age, debut age, number of lifetime partners, baseline STI status, insurance, and pregnancy history. **Group Description:** H0: Women in TECHN arm had 72 hour visit with same frequency as women in control arm. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 92.2 **Statistical Comment:** Adjusted for age, debut age, number of lifetime partners, baseline STI status (any vs none), insurance, and if woman had prior pregnancy. **Statistical Method:** Chi-squared **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.05 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is for intervention arm relative to control. **Group Description:** H0: Women in TECHN arm reported complete adherence to medication regimen (yes or no) with same frequency as women in control arm. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.084 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.6 **Statistical Comment:** Adjusted for age, debut age, number of lifetime partners, pregnancy history, baseline STI status (any versus none), and insurance. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.34 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is for the chances of partner notification among TECH N recipients, relative to those in control arm. **Group Description:** H0: Women in TECHN arm notified their partners about their diagnoses more often than women in the control arm. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.867 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.9 **Statistical Comment:** Adjusted for age, debut age, number of lifetime partners, pregnancy history, baseline STI status (any versus none), and insurance. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.19 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is for partners of TECH-N recipients versus partners of women in control arm. **Group Description:** H0: Partners of women receiving the TECH-N intervention were treated more often than the partners of women in the control arm. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.153 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.6 **Statistical Comment:** Adjusted for age, debut age, number of lifetime partners, pregnancy history, baseline STI status (any versus none), and insurance. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.86 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.06 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is for women in the TECH-N arm relative to women in the control arm. **Group Description:** H0: Women in the TECHN arm practiced temporary sexual abstinence for two weeks after their diagnosis more often than those in the control arm. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.351 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.0 **Statistical Comment:** Adjusted for age, debut age, number of lifetime partners, pregnancy history, baseline STI status (any versus none), and insurance. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 131 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** STI testing (positive Neisseria gonorrhoeae (GC) or Chlamydia trachomatis CT) tested at 90 days using nucleic acid amplification testing (NAAT). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Adolescent and young adult women with pelvic inflammatory disease (PID) in Baltimore City randomized to the intervention or control group and also had results for chlamydia (CT) and gonorrhea (GC) at 90 days after enrollment. All enrolled participants were followed as long as possible for entire 90 days. **Reporting Status:** POSTED **Time Frame:** 90 Days **Title:** Number of Participants With Positive Sexually Transmitted Infection Test (STI) **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants receive the Technology Enhanced Community Health Nursing Visit (community health nursing visits within 5 days during which Sister to Sister and clinical assessment performed and text-messaging support Technology Enhanced Community Health Nursing: -Text-messaging (twice daily medication reminders w/ positive adherence messages, positive sexual health messages throughout the 30 day treatment period) -Enhanced community health nursing visit on day 3-5, includes DEBI STI/HIV prevention component (Sister to Sister Teen) **ID:** OG000 **Title:** TECH-N ##### Group **Description:** Participants receive enhanced standard of care **ID:** OG001 **Title:** Control #### Outcome Measure 2 **Description:** Completion of 72-hour assessment visit by medical provider, medication adherence (self-reported), partner notification, partner treatment, and temporary sexual abstinence **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Chi-square test results from participants in the intervention and control groups who had data on adherence to treatment. Out of 149 enrolled in the intervention arm, 10 were lost to followup by 72 hours. Out of 137 enrolled in the control arm, 15 were lost by 72 hours and so are missing this outcome measure. **Reporting Status:** POSTED **Time Frame:** Day 15 **Title:** Number of Participants That Adhered to Self-treatment **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants receive the Technology Enhanced Community Health Nursing Visit (community health nursing visits within 5 days during which Sister to Sister and clinical assessment performed and text-messaging support Technology Enhanced Community Health Nursing: -Text-messaging (twice daily medication reminders w/ positive adherence messages, positive sexual health messages throughout the 30 day treatment period) -Enhanced community health nursing visit on day 3-5, includes evidence-based STI/HIV prevention component (Sister to Sister Teen) **ID:** OG000 **Title:** TECH-N ##### Group **Description:** Participants receive enhanced standard of care **ID:** OG001 **Title:** Control ### Participant Flow Module #### Group **Description:** Experimental: TECH-N Participants receive the Technology Enhanced Community Health Nursing Visit (community health nursing visits within 5 days during which Sister to Sister and clinical assessment performed and text-messaging support **ID:** FG000 **Title:** Intervention #### Group **Description:** Participants receive enhanced standard of care **ID:** FG001 **Title:** Control #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 149 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 137 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 135 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 125 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 12 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03314779 **Brief Title:** Combined Intracerebral and Jugular Bulb Microdialysis **Official Title:** Continuous Monitoring of Cerebral Metabolic State. Combined Intracerebral and Jugular Bulb Microdialysis in Neurocritical Care. #### Organization Study ID Info **ID:** 20150173 #### Organization **Class:** OTHER **Full Name:** Odense University Hospital ### Status Module #### Completion Date **Date:** 2018-07-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-02-28 **Type:** ACTUAL **Last Update Submit Date:** 2019-02-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-07-01 **Type:** ACTUAL #### Start Date **Date:** 2017-08-28 **Type:** ACTUAL **Status Verified Date:** 2019-02 #### Study First Post Date **Date:** 2017-10-19 **Type:** ACTUAL **Study First Submit Date:** 2017-09-12 **Study First Submit QC Date:** 2017-10-18 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Region of Southern Denmark #### Lead Sponsor **Class:** OTHER **Name:** Odense University Hospital #### Responsible Party **Investigator Affiliation:** Odense University Hospital **Investigator Full Name:** Axel Forsse **Investigator Title:** MD, PhD-fellow **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The first aim of this study is to investigate the frequency and severity of a specific pathological metabolic pattern, mitochondrial dysfunction, of the brain in comatose patients under neurocritical care. This pattern is recognized as a complication after compromised blood flow to the brain and may be amenable to treatment. The other main aim of this study is to correlate patterns of metabolites between brain and jugular venous blood. It is probable but not proven that jugular venous microdialysis can mirror the global metabolic state of the brain. **Detailed Description:** Purpose To describe the incidence of cerebral mitochondrial dysfunction in comatose patients admitted to the Neurointensive Care Unit (NICU) at Odense University Hospital and to evaluate the possible correlations between cerebral and jugular bulb microdialysis in an effort to develop new, effective and less invasive diagnostical tools for relevant patient groups. Background The hallmark of several serious neurological and neurosurgical disorders including severe traumatic brain injury, intracranial haemorrhage, cerebral infection and global hypoxic injury after cardiac arrest, is that the primary insult is out of reach for therapeutic intervention. Secondary injuries however, ensuing in the days to weeks after the primary insult are amenable to prevention or treatment. Inflammation, transient ischemia, free radical formation, cellular Ca2+-influx and mitochondrial dysfunction are therefore all examples of current research topics in neurointensive care. The research group has a long history of experimental and clinical work in the area of cerebral metabolism in neurocritical disease. In recent years neuromonitoring with cerebral microdialysis has been a main focus, as well as mitochondrial dysfunction as a possible therapeutic target . In 2004 the investigators showed how monitoring SAH-patients with cerebral microdialysis could predict delayed neurological deterioration/vasospasm related complications, results that were corroborated by later external studies. In 2012 and 2014, results have been published showing how to diagnose mitochondrial dysfunction on the basis of the biochemical patterns of cerebral microdialysis experimentally as well as clinically. Briefly, a cerebrochemical pattern with elevated lactate/pyruvate-ratio with simultaneous normal or supranormal levels of pyruvate and glucose seen together with normal tissue oxygen monitoring indicates mitochondrial dysfunction. Mitochondrial dysfunction most likely plays a key role in the worsening of outcome in a variety cerebral pathological conditions, and might be amenable to pharmacologic intervention. The microdialysis technique is based on a thin probe with a semipermeable membrane being inserted in affected brain tissue, collecting interstitial fluid from a small area surrounding the probe. The fluid is analysed for metabolites, proteins or pharmacological substances and has earlier been shown to be of great value in guiding NICU care and prognostication. One problem with the technique is, however, that the measurements are regional and limited to the very small sampling volume of the probe. Another obstacle is that the technique is intracranial invasive. Aims In the current prospective cohort study, the investigators will describe the incidence of mitochondrial dysfunction in a patients admitted to the NICU with severe subarachnoid haemorrhage (SAH). As patients suffering from SAH often have a non-ischemic cerebral metabolic affliction, a global cerebral measurement would presumably be as useful or more so than a focal measurement from only a very small regional brain volume. The investigators wish to evaluate a new method of monitoring, namely microdialysis of cerebral venous blood drainage. The cerebral venous drainage passes almost without exception through the jugular bulbs, left or right sided majority depending on dominance. The investigators will compare results of regional cerebral and venous measurements in order to confirm the hypothesis that metabolic disturbances of the brain are mirrored in the venous blood drainage in the jugular bulb. A pilot study of patients undergoing open heart surgery has confirmed significant differences in lactate and pyruvate in arterial systemic vs jugular venous blood. Yet unpublished data from this groups porcine experimental model supports the possibility of global metabolic venous monitoring. Perspectives If jugular bulb microdialysis can be confirmed to give a reliable global estimate of cerebral metabolic state it might be possible to a implement a new, less invasive diagnostic tool for NICU-patients. Surrogate measures in use today as e.g. NIRS (Near Infrared Spectroscopy) correlate poorly to cerebral metabolic status. ### Conditions Module **Conditions:** - Subarachnoid Hemorrhage - Hypoxia Ischemia, Cerebral - TBI - Meningitis ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Hourly samples of lactate (mM) and pyruvate (mikroM) are assessed using microdialysis measurements in brain and jugular bulb. The LP-ratio is calculated and compared at each timepoint. **Measure:** Correlations of lactate/pyruvate-ratio (LP-ratio) calculated by dividing lactate concentration in mM by pyruvate concentration in mikroM, in cerebral and venous microdialysis **Time Frame:** Patients are monitored a mean of 5 days with hourly analysis. #### Secondary Outcomes **Description:** Cerebral and jugular bulb microdialysis measurements of glucose (mM)compared for co-variation. **Measure:** Correlations of microdialysis values of glucose. **Time Frame:** Mean 5 day measurements **Description:** 6 month modified Rankin Scale (mRS) will be assessed at outpatient clinic. The mRS is the most widely used scale for measuring degree of disability in stroke trials, The scale ranges from 0 to 6, where 0 means no symptoms and 6 is dead. **Measure:** Modified Rankin scale of outcome. **Time Frame:** 6 months **Description:** Microdialysis results will be analysed for amount (hours) of mitochondrial dysfunction, defined as normal cerebral P02-measurements (mmHg), in combination with high LP-ratio (ratio) and simultaneous normal or high pyruvate concentration (mikroM). **Measure:** Evaluation of mitochondrial dysfunction under study period. **Time Frame:** calculations based on mean 5-day measurements per patient. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Glasgow coma score \<8. * Suspicion of intracranial pathology Exclusion Criteria: * Suspected and/or Untreated coagulopathy * Consent from closest of kin not given **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients admitted to the neurointensive care unit at Odense University Hospital. ### Contacts Locations Module #### Locations **Location 1:** **City:** Odense **Country:** Denmark **Facility:** Odense University Hospital **Zip:** 5000 #### Overall Officials **Official 1:** **Affiliation:** Consultant, Professor, Research leader **Name:** Frantz Rom Poulsen, MD, PhD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Nordstrom CH, Koskinen LO, Olivecrona M. Aspects on the Physiological and Biochemical Foundations of Neurocritical Care. Front Neurol. 2017 Jun 19;8:274. doi: 10.3389/fneur.2017.00274. eCollection 2017. **PMID:** 28674514 **Citation:** Nordstrom CH, Rehncrona S, Siesjo BK. Restitution of cerebral energy state, as well as of glycolytic metabolites, citric acid cycle intermediates and associated amino acids after 30 minutes of complete ischemia in rats anaesthetized with nitrous oxide or phenobarbital. J Neurochem. 1978 Feb;30(2):479-86. doi: 10.1111/j.1471-4159.1978.tb06553.x. No abstract available. **PMID:** 624953 **Citation:** Jacobsen A, Nielsen TH, Nilsson O, Schalen W, Nordstrom CH. Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage. Acta Neurol Scand. 2014 Sep;130(3):156-63. doi: 10.1111/ane.12258. Epub 2014 May 3. **PMID:** 24796605 **Citation:** Nielsen TH, Olsen NV, Toft P, Nordstrom CH. Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets. Acta Anaesthesiol Scand. 2013 Jul;57(6):793-801. doi: 10.1111/aas.12092. Epub 2013 Mar 18. **PMID:** 23495747 **Citation:** Nielsen TH, Bindslev TT, Pedersen SM, Toft P, Olsen NV, Nordstrom CH. Cerebral energy metabolism during induced mitochondrial dysfunction. Acta Anaesthesiol Scand. 2013 Feb;57(2):229-35. doi: 10.1111/j.1399-6576.2012.02783.x. Epub 2012 Sep 28. **PMID:** 23017022 **Citation:** Poulsen FR, Schulz M, Jacobsen A, Andersen AB, Larsen L, Schalen W, Nielsen TH, Nordstrom CH. Bedside evaluation of cerebral energy metabolism in severe community-acquired bacterial meningitis. Neurocrit Care. 2015 Apr;22(2):221-8. doi: 10.1007/s12028-014-0057-x. **PMID:** 25142826 **Citation:** Skjoth-Rasmussen J, Schulz M, Kristensen SR, Bjerre P. Delayed neurological deficits detected by an ischemic pattern in the extracellular cerebral metabolites in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2004 Jan;100(1):8-15. doi: 10.3171/jns.2004.100.1.0008. **PMID:** 14743906 **Citation:** Rostami E, Engquist H, Howells T, Johnson U, Ronne-Engstrom E, Nilsson P, Hillered L, Lewen A, Enblad P. Early low cerebral blood flow and high cerebral lactate: prediction of delayed cerebral ischemia in subarachnoid hemorrhage. J Neurosurg. 2018 Jun;128(6):1762-1770. doi: 10.3171/2016.11.JNS161140. Epub 2017 Jun 2. **PMID:** 28574309 **Citation:** Hutchinson PJ, Jalloh I, Helmy A, Carpenter KL, Rostami E, Bellander BM, Boutelle MG, Chen JW, Claassen J, Dahyot-Fizelier C, Enblad P, Gallagher CN, Helbok R, Hillered L, Le Roux PD, Magnoni S, Mangat HS, Menon DK, Nordstrom CH, O'Phelan KH, Oddo M, Perez Barcena J, Robertson C, Ronne-Engstrom E, Sahuquillo J, Smith M, Stocchetti N, Belli A, Carpenter TA, Coles JP, Czosnyka M, Dizdar N, Goodman JC, Gupta AK, Nielsen TH, Marklund N, Montcriol A, O'Connell MT, Poca MA, Sarrafzadeh A, Shannon RJ, Skjoth-Rasmussen J, Smielewski P, Stover JF, Timofeev I, Vespa P, Zavala E, Ungerstedt U. Consensus statement from the 2014 International Microdialysis Forum. Intensive Care Med. 2015 Sep;41(9):1517-28. doi: 10.1007/s00134-015-3930-y. **PMID:** 26194024 **Citation:** Tachtsidis I, Tisdall MM, Pritchard C, Leung TS, Ghosh A, Elwell CE, Smith M. Analysis of the changes in the oxidation of brain tissue cytochrome-c-oxidase in traumatic brain injury patients during hypercapnoea: a broadband NIRS study. Adv Exp Med Biol. 2011;701:9-14. doi: 10.1007/978-1-4419-7756-4_2. **PMID:** 21445763 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000012818 - Term: Signs and Symptoms, Respiratory - ID: D000020300 - Term: Intracranial Hemorrhages - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000090862 - Term: Neuroinflammatory Diseases - ID: D000002534 - Term: Hypoxia, Brain ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M4185 - Name: Hypoxia - Relevance: HIGH - As Found: Hypoxia - ID: M11564 - Name: Meningitis - Relevance: HIGH - As Found: Meningitis - ID: M16135 - Name: Subarachnoid Hemorrhage - Relevance: HIGH - As Found: Subarachnoid Hemorrhage - ID: M5794 - Name: Brain Ischemia - Relevance: HIGH - As Found: Ischemia, Cerebral - ID: M22660 - Name: Hypoxia-Ischemia, Brain - Relevance: HIGH - As Found: Hypoxia Ischemia, Cerebral - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown - ID: M22113 - Name: Intracranial Hemorrhages - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M2803 - Name: Neuroinflammatory Diseases - Relevance: LOW - As Found: Unknown - ID: M5783 - Name: Hypoxia, Brain - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013345 - Term: Subarachnoid Hemorrhage - ID: D000008581 - Term: Meningitis - ID: D000002545 - Term: Brain Ischemia - ID: D000020925 - Term: Hypoxia-Ischemia, Brain - ID: D000006470 - Term: Hemorrhage - ID: D000000860 - Term: Hypoxia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03529279 **Brief Title:** CNG Staging Compared With 8th UICC of NPC for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy **Official Title:** CNG Staging Compared With UICC Eighth Staging of Nasopharyngeal Carcinoma for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy： a Multicenter, Open Label, Randomized Controlled, Non-inferiority Clinical Trial #### Organization Study ID Info **ID:** B2018-030-01 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2026-06-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2018-05-18 **Type:** ACTUAL **Last Update Submit Date:** 2018-05-07 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-06-12 **Type:** ESTIMATED #### Start Date **Date:** 2018-06-12 **Type:** ESTIMATED **Status Verified Date:** 2018-05 #### Study First Post Date **Date:** 2018-05-18 **Type:** ACTUAL **Study First Submit Date:** 2018-05-06 **Study First Submit QC Date:** 2018-05-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** Yun-fei Xia **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Due to the increase of tumor control rate and survival rate in era of IMRT, the role of the seventh edition of UICC/AJCC staging system in predicting prognosis is becoming weaker and inaccurate. Therefore, we put forward a new staging for the clinical staging of NPC in the era of IMRT without changing the current T, N, M staging definition of the 7th of the UICC/AJCC staging system. We call this new stage "Cooperative Nasopharyngeal Carcinoma Group" stage, namely CNG stage. In CNG stage, the clinical stages were reduced to three stages, namely, CNG I stage includes T1-3N0-1M0 and T1-2N2M0, CNG II stage includes T3N2M0, T4N0-2M0 and TanyN3M0, CNG III stage includes TanyNanyM1. For CNG I stage, the IMRT alone is sufficient. If EBV-DNA copies is more than 0 copy/ml, concurrent chemoradiotherapy will be given. For CNG II stage, patients can benefit from combined radiotherapy and chemotherapy. For CNG III stage, patients are recommended for systemic chemotherapy plus local radiotherapy (primary focus, neck drainage area and distant metastasis). This year, UICC/AJCC has proposed an eighth edition of NPC staging system. The eighth version is mainly changed in the definition and refinement of the anatomic location compared with the seventh edition. This is different from our new CNG staging concept. Therefore, CNG staging and its treatment strategy was used as the experimental group, and the eighth edition of UICC/AJCC staging with NCCN guiding treatment was used as the control group. The open and randomized controlled clinical study was conducted. The purpose of this study was to evaluate in the era of IMRT, CNG staging can be better than UICC/AJCC eighth clinical staging for treatment decision-marking and selection of chemotherapy and radiotherapy, and differentiating differences in prognosis in each clinical stage. The survival results based on CNG staging and its treatment are not inferior to the survival results of the NCCN guide therapy based on the eighth edition UICC/AJCC staging, to avoid chemotherapy for some of the patients, and to improve the outcome of metastatic patients. **Detailed Description:** The seventh edition of the UICC/AJCC staging system, which is widely used in recent years, is based on survival data in the traditional era of radiotherapy. However, the survival of nasopharyngeal cancer patients has been greatly improved in the era of modern radiation therapy, which IMRT (Intension Modulated Radiotherapy) is widely used. Even with radiotherapy alone, the 5 year disease specific survival rate of nasopharyngeal carcinoma with stage I-II is more than 95%, the 3 year overall survival rate of non metastatic III-IV patients is about 75%, and the 5 year overall survival rate is about 80%. The 5 year survival rate of metastatic nasopharyngeal carcinoma can reach more than 20% with systemic treatment. Due to the increase of tumor control rate and survival rate in era of IMRT, the role of the seventh edition of UICC/AJCC staging system in predicting prognosis is becoming weaker and inaccurate. Therefore, in the previous study, we put forward a new staging for the clinical staging of nasopharyngeal carcinoma in the era of IMRT without changing the current T, N, M staging definition of the seventh edition of the UICC/AJCC staging system. We call this new stage "Cooperative Nasopharyngeal Carcinoma Group" stage, namely CNG stage. In CNG stage, the clinical stages were reduced to three stages, namely, CNG I stage includes T1-3N0-1M0 and T1-2N2M0, CNG II stage includes T3N2M0, T4N0-2M0 and TanyN3M0, CNG III stage includes TanyNanyM1, and the 5 year DSS (Disease specific survival) is 93.3%, 72.7%, and 24%, respectively, with a significant difference. This year, UICC/AJCC has proposed an eighth edition of nasopharyngeal carcinoma staging system based on the revision of the seventh edition. The main updates are: (1) add the definition of the T0 phase, that is, the EBV positive cervical lymph node metastases with uncertain primary foci, and (2) the invasion of the adjacent muscles (including the pterygus, the extradypterygus, and the anterior vertebroid muscle) into T2; (3) replace the "masticatory muscle space" and "subtemporal fossa" in the previous T4 definition with a specific description of soft tissue invasion; (4) change the supraclavicular fossa to the lower neck (defined as the lymph node metastases below the subchondral edge); (5) N3a and N3b are combined called N3, and it is defined as a single / double neck lymph node with long diameter \> 6cm, and/or below the subchondral subchondral edge; (6) the IVA stage (T4 N0-2 M0) and the IVB stage (anyT N3 M0) are combined called IVA stage; (7) the IVC stage (anyT anyN) is changed to IVB stage. The eighth version is mainly changed in the definition and refinement of the anatomic location compared with the seventh edition. Except for the migration of the adjacent muscle invasion, and the other changes are not significant. The upper bound of N3 is moved from the supraclavicular fossa to the subchondral edge in N staging. This is different from our new CNG staging concept. CNG staging of nasopharyngeal carcinoma is related to the unique biological behavior of nasopharyngeal carcinoma, which is consistent with the three clinical patterns of nasopharyngeal carcinoma, namely, non metastasis, tendency to metastasis and metastasis. The pattern of tendency to metastasis was related to the late T and N staging. Based on the biological behavior and clinical survival data of NPC, we further proposed the treatment strategy of nasopharyngeal carcinoma under the guidance of CNG staging, that is, the CNG I stage is consistent with the non metastasis model, and the IMRT alone is sufficient. The CNG II stage is consistent with the tendency to metastasis mode, which can benefit from combined radiotherapy and chemotherapy. The CNG III stage is metastatic mode, which is recommended for systemic chemotherapy plus local radiotherapy (primary focus, neck drainage area and distant metastasis). In clinical practice, we suggest that for patients with CNG I stage, if EBV-DNA copies is more than 0 copy/ml, concurrent chemoradiotherapy will be given. Therefore, CNG staging and its treatment strategy was used as the experimental group, and the eighth edition of UICC/AJCC staging with NCCN guiding treatment was used as the control group. The open and randomized controlled clinical study was conducted. The purpose of this study was to evaluate in the era of IMRT, CNG staging can be better than UICC/AJCC eighth clinical staging for treatment decision-marking and selection of chemotherapy and radiotherapy, and differentiating differences in prognosis in each clinical stage. The survival results based on CNG staging and its treatment are not inferior to the survival results of the NCCN guide therapy based on the eighth edition UICC/AJCC staging, to avoid chemotherapy for some of the patients, and to improve the outcome of metastatic patients. ### Conditions Module **Conditions:** - Nasopharyngeal Carcinoma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1324 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patients in the Experimental Group are allocated to receive CNG staging and CNG chemotherapy strategy and CNG radiation strategy **Intervention Names:** - Drug: CNG Chemotherapy - Radiation: CNG Radiation **Label:** Experimental Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The patients in the Controlled Group are allocated to receive the eighth edition of UICC/AJCC staging and NCCN chemotherapy strategy and NCCN radiation strategy **Intervention Names:** - Drug: NCCN Chemotherapy - Radiation: NCCN Radiation **Label:** Controlled Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental Group **Description:** CNG I, IMRT plus oral adjuvant chemotherapy, if EBV-DNA \> 0,according to CNG II. CNG II, IMRT + concurrent chemotherapy + oral adjuvant chemotherapy. CNG III, systemic chemotherapy, plus IMRT. Chemotherapy strategy: Concurrent chemotherapy, 5-Fu + nedaplatin (cisplatin), every 28 days; 5-Fu 500mg/m2. D, civ d1-d5, nedaplatin (cisplatin) 80mg (70mg) /m2. D, D1. Systemic chemotherapy, 5-Fu + nedaplatin (cisplatin), every 60 days; 5-Fu (100 - 200 mg/m2. D) civ for 30 days, nedaplatin (cisplatin) 80mg (70mg) /m2. D, D1,D28. Aim to achieve CR in imaging.Oral adjuvant chemotherapy, tegafon (400 mg, QID) and Calcium Folinate Tablets (30 mg, QID). Oral 10 days and stop 20 days, 3 months/course. After 6 courses, oral 10 days and stop 50 days, half year/course, 6-7 courses, lasted for 5 years. **Name:** CNG Chemotherapy **Other Names:** - Chemotherapy strategy for experimental group **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Controlled Group **Description:** UICC I, IMRT. UICC II-IVA, concurrent chemoradiotherapy ± adjuvant chemotherapy, or induced chemotherapy plus concurrent chemoradiotherapy. UICC IVB, platinum based combined chemotherapy, followed by IMRT or concurrent chemoradiotherapy, or concurrent chemoradiotherapy. Chemotherapy strategy: Concurrent cisplatin with or without cisplatin plus 5-Fu or carboplatin combined with 5-Fu adjuvant chemotherapy; The combined chemotherapy regimen of IVB stage patients may choose cisplatin or carboplatin plus docetaxel or paclitaxel, cisplatin plus 5-Fu, carboplatin and cetuximab, cisplatin plus gemcitabine, and gemcitabine. The combination of vinorelbine and cisplatin, carboplatin, paclitaxel, docetaxel, 5-Fu, methotrexate, gemcitabine and capecitabine can be used in combination with radiotherapy. **Name:** NCCN Chemotherapy **Other Names:** - Chemotherapy strategy for controlled group **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Experimental Group **Description:** IMRT technique. GTV was given to 6810cGy, CTV1 was given to 6000cGy, and CTV2 was given to 4800-5400cGy. 30 fractions, daily, QW1-5. CT-SIM or MR-CIM was evaluated every 10 fractions. If CR for CNG I and II patients at 10 fractions, radiotherapy were given 25 fractions, that was, GTV was given to 5675cGy, CTV1 was given 5000cGy, and CTV2 was given 4000-4500cGy, 25 fractions, daily, QW1-5. If tumor reduced less than 50% at 20 fractions, GTV was modified according to tumor size at 20 fractions. The modified GTV was given 300cGy/F×5 after 25 fractions; the original CTV1 and CTV2 were unchanged, that is, GTV was given to 5675cGy/25Fr+1500cGy/5Fr and CTV1 was given to 6000cGy/30Fr, CTV2 was given 4800-5400cGy/30Fr. **Name:** CNG Radiation **Other Names:** - Radiation for experimental group **Type:** RADIATION #### Intervention 4 **Arm Group Labels:** - Controlled Group **Description:** IMRT technique. When IMRT alone, GTV were given (1) 66Gy (2.2Gy/Fr) to 70-70.2 Gy (1.8-2.0 Gy/Fr), QW1-5, 6-7 weeks; (2) 69.96 Gy (2.12 Gy/Fr), 6-7 weeks; CTV1-2 were given 44-50 (2.0 Gy/Fr) to 54-63 (1.8 Gy/Fr). When combined with chemotherapy, GTV were given 70-70.2 Gy (1.8-2.0 Gy/Fr), QW1-5, 7 weeks; CTV1-2 were given 44-50 Gy (2 Gy/Fr) to 54-63 Gy (1.8 Gy/Fr). When palliative radiotherapy, 50Gy/20Fr; 37.5 Gy/15Fr (if tolerable, increases 5 fractions to 50Gy); 30Gy/10Fr, 30Gy/5Fr, 2 fractions per week, interval more than 3 days; 44.4Gy/12Fr was divided into 3 cycles, 2 fractions a day, 6 hours of interval, 2 consecutive days and 3-4 weeks between two cycles. After second cycles, the treatment plan must completely avoid the irradiation of the spinal cord. **Name:** NCCN Radiation **Other Names:** - Radiation for controlled group **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** 5-year overall survival **Measure:** Overall Survival (OS) **Time Frame:** From the date of randomization until the date of death, assessed up to 60 months #### Secondary Outcomes **Description:** The standard scores assessed by EORTC QOL scale decreased by more than 10 points **Measure:** Quality of life **Time Frame:** From the date of radiotherapy begin, every week during radiotherapy, assessed up to 60 months **Description:** 5-year recurrence free survival **Measure:** Recurrence free survival (RFS) **Time Frame:** From the date of randomization until the date of first recurrence, assessed up to 60 months **Description:** 5-year distant metastasis free survival **Measure:** Distant metastasis free survival (DMFS) **Time Frame:** From the date of randomization until the date of first distant metastasis, assessed up to 60 months **Description:** 5-year disease specific survival **Measure:** Disease specific survival (DSS) **Time Frame:** From the date of randomization until the date of death from tumor, assessed up to 60 months **Description:** all the target lesions disappeared, no new lesions appeared, and the tumor markers were normal, and maintained for at least 4 weeks, according to RECIST **Measure:** Complete remission (CR) **Time Frame:** From the date of randomization, 3 months after radiotherapy **Description:** according to NCI CTC 4.0 **Measure:** Incidence of side effects associated with tumor therapy **Time Frame:** From the date of randomization up to 60 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pathologically confirmed and previously untreated nasopharyngeal carcinoma * Non T1N0M0 patient according to UICC/AJCC seventh edition staging system * Age ≥ 18 years and \< 65 years * Karnofsky performance status (KPS) score ≥ 70 * Adequate normal organ function * No history of other malignant tumors * No serious mental disorder (schizophrenia, delusion of victimization, manic depression, and drug induced anxiety) * No AIDS, active pulmonary tuberculosis and other serious immunodeficiency diseases * No communication barrier, can answer the question * Sign informed consent under voluntary circumstances, complete treatment and follow up as required Exclusion Criteria: * Poor compliance * Investigators consider as inappropriate for enrolling into this study **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** xiayf@sysucc.org.cn **Name:** Yun-fei Xia, M.D **Phone:** 86-13602805461 **Role:** CONTACT **Contact 2:** **Email:** chenchen@sysucc.org.cn **Name:** Chen Chen, M.D **Phone:** 86-13570487011 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Sun Yat-sen University **Name:** Yun-fei Xia, M.D **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009303 - Term: Nasopharyngeal Neoplasms - ID: D000010610 - Term: Pharyngeal Neoplasms - ID: D000010039 - Term: Otorhinolaryngologic Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009302 - Term: Nasopharyngeal Diseases - ID: D000010608 - Term: Pharyngeal Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M1730 - Name: Nasopharyngeal Carcinoma - Relevance: HIGH - As Found: Nasopharyngeal Carcinoma - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12254 - Name: Nasopharyngeal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M13517 - Name: Pharyngeal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12962 - Name: Otorhinolaryngologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12253 - Name: Nasopharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M13515 - Name: Pharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - Relevance: LOW - As Found: Unknown - ID: T4047 - Name: Nasopharyngeal Carcinoma - Relevance: HIGH - As Found: Nasopharyngeal Carcinoma ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000077274 - Term: Nasopharyngeal Carcinoma ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M315 - Name: Cetuximab - Relevance: LOW - As Found: Unknown - ID: M6191 - Name: Leucovorin - Relevance: LOW - As Found: Unknown - ID: M8600 - Name: Fluorouracil - Relevance: LOW - As Found: Unknown - ID: M29233 - Name: Levoleucovorin - Relevance: LOW - As Found: Unknown - ID: M11703 - Name: Methotrexate - Relevance: LOW - As Found: Unknown - ID: M19537 - Name: Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M231 - Name: Albumin-Bound Paclitaxel - Relevance: LOW - As Found: Unknown - ID: M377 - Name: Capecitabine - Relevance: LOW - As Found: Unknown - ID: M6182 - Name: Cisplatin - Relevance: LOW - As Found: Unknown - ID: M2985 - Name: Gemcitabine - Relevance: LOW - As Found: Unknown - ID: M1668 - Name: Docetaxel - Relevance: LOW - As Found: Unknown - ID: M18650 - Name: Carboplatin - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M1710 - Name: Vinorelbine - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M192636 - Name: Nedaplatin - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00895479 **Acronym:** AdV-VANTAGE **Brief Title:** Adenovirus Vascular Endothelial Growth Factor (VEGF) Therapy in Vascular Access - Novel Trinam AGainst Control Evidence **Official Title:** A Phase III, Randomized, Controlled, Open Label, Multicenter Study of the Efficacy and Safety of Trinam® (EG004); an Assessment of Primary Unassisted Patency and Survival of Vascular Access Grafts in Hemodialysis Patients With End Stage Renal Disease #### Organization Study ID Info **ID:** Ark 103 #### Organization **Class:** INDUSTRY **Full Name:** Ark Therapeutics Ltd ### Status Module #### Completion Date **Date:** 2011-09 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2010-11-19 **Type:** ESTIMATED **Last Update Submit Date:** 2010-11-18 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2011-09 **Type:** ESTIMATED #### Start Date **Date:** 2009-04 **Status Verified Date:** 2010-11 #### Study First Post Date **Date:** 2009-05-08 **Type:** ESTIMATED **Study First Submit Date:** 2009-05-07 **Study First Submit QC Date:** 2009-05-07 **Why Stopped:** Strategic reasons. Seeking partner for future development. ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Ark Therapeutics Ltd #### Responsible Party **Old Name Title:** Director of Research and Development **Old Organization:** Ark Therapetics Ltd ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Patients in renal failure on hemodialysis depend on adequate and sustained vascular access. This can be achieved by surgical placement of a synthetic polytetrafluoroethylene (PTFE) graft. These patients frequently experience graft complications arising from the development of smooth muscle cell (SMC) neointimal hyperplasia in the proximity of the graft-vein anastomosis. Such complications eventually lead to stenosis, access thrombosis and graft failure. Trinam® is being developed to prolong graft survival. It is a combination product consisting of a replication deficient Adenovirus containing the human Vascular Endothelial Growth Factor D (Ad-VEGF-D) gene and a biodegradable local delivery device (collar) made of collagen. At the end of the surgical procedure to insert the PTFE graft the collagen collar is applied around the anastomosis and sealed with a collagen surgical sealant. This procedure creates a reservoir between the site of anastomosis and the collagen collar. The adenoviral vector is then injected into this reservoir, localizing the expression of the transgene to the site of the anastomosis. Expression of VEGF-D has been shown to have a vascular protective role and inhibit SMC neointimal proliferation, therefore expression of VEGF-D should prolong graft survival. ### Conditions Module **Conditions:** - End Stage Renal Disease **Keywords:** - End Stage Renal Disease - ESRD - Hemodialysis - Access Graft ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 250 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Graft placement plus Trinam therapy **Intervention Names:** - Procedure: Graft placement surgery plus Trinam therapy **Label:** Trinam **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Graft placement surgery alone **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Trinam **Description:** Trinam arm: graft placement surgery plus 1ml perivascular administration of Trinam vector. Control arm: graft placement surgery **Name:** Graft placement surgery plus Trinam therapy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Primary Unassisted Patency **Time Frame:** 18 Months #### Secondary Outcomes **Measure:** Graft Survival. Number and rate of graft interventions. **Time Frame:** 2.5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with end stage renal disease undergoing either initial placement or replacement (after failure of previous vascular access) of an end-to-side or end-to-end 6.0 mm synthetic PTFE arteriovenous hemodialysis access arm graft. * Male or female aged 18 years or over. * Patients who signed the informed consent form. * Patients who are expected to undergo dialysis at nominated facilities for the duration of the study. * Patients who have agreed to participate in the additional four year gene therapy safety monitoring. * Patients who are willing to agree they will not have a kidney transplant for four weeks post treatment with Trinam®. * Patients who have undergone arterial and venous mapping to ensure an adequate and appropriate access site is available for placement of either an end-to-side or an end-to-end 6.0 mm synthetic PTFE arteriovenous hemodialysis access arm graft with or without the addition of Trinam®. Exclusion Criteria: * Patients who are unable to understand and sign the consent form. * Patients undergoing surgical revision of an existing graft. * Exclude patients from the study if they have moderate or severe macular edema moderate or severe proliferative diabetic retinopathy * Current diagnosis of cancer with exception of non-melanoma skin cancers. * Hepatic dysfunction defined as AST and / or ALT \> 2 times the Upper Limit of Normal. * Diabetic patients with Hemoglobin A1C value of \>10%. * White blood cell (WBC) count \< 2.0 x 109/L. * Prior anticoagulant therapy within 14 days prior to surgery is an exclusion. * Known sensitivity to collagen. * Pregnancy, lactation or lack of effective contraception both in women and in men of childbearing potential. * Previous participation in any Trinam® study. * Receipt of any investigational drug within 30 days prior to study enrollment or participation in any concurrently running trial involving investigational intervention. * Any medical or psychiatric condition that compromises the ability to participate in the study. * Known or suspected drug or alcohol abuse in the past six months. * Life expectancy of less than one year. * Known immunodeficiency disease. * Known chronic hepatitis of viral or non-viral etiology and / or a history of decompensated liver failure of any etiology. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Long Beach **Country:** United States **Facility:** Long Beach VA Healthcare System **State:** California **Zip:** CA 90822 **Location 2:** **City:** Paducah **Country:** United States **Facility:** Four Rivers Clinical Research Inc **State:** Kentucky **Zip:** KY 42003 **Location 3:** **City:** Baton Rouge **Country:** United States **Facility:** Baton Rouge General Hospital **State:** Louisiana **Zip:** LA 70809 **Location 4:** **City:** Shreveport **Country:** United States **Facility:** Louisiana State University Health Sciences Center **State:** Louisiana **Zip:** LA 71103 **Location 5:** **City:** St Louis **Country:** United States **Facility:** Washington University School of Medicine **State:** Missouri **Zip:** MO 63110 **Location 6:** **City:** New York **Country:** United States **Facility:** Mount Sinai Medical Center **State:** New York **Zip:** NY 10029 **Location 7:** **City:** New York **Country:** United States **Facility:** St Luke's Roosevelt Hospital **State:** New York **Zip:** NY10025 **Location 8:** **City:** Durham **Country:** United States **Facility:** Duke University Medical Center **State:** North Carolina **Zip:** NC 27710 **Location 9:** **City:** Cincinnati **Country:** United States **Facility:** University of Cincinnati **State:** Ohio **Zip:** OH 45267 **Location 10:** **City:** Columbus **Country:** United States **Facility:** Ohio State University Division of Nephrology **State:** Ohio **Zip:** OH 43210 **Location 11:** **City:** Lubbock **Country:** United States **Facility:** Texas Tech University Medical Center **State:** Texas **Zip:** TX 79415 **Location 12:** **City:** Seattle **Country:** United States **Facility:** Harborview Medical Center **State:** Washington **Zip:** WA 98104 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic - ID: D000051437 - Term: Renal Insufficiency - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC01 - Name: Infections - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Renal Disease - ID: M10699 - Name: Kidney Failure, Chronic - Relevance: HIGH - As Found: End Stage Renal Disease - ID: M3610 - Name: Adenoviridae Infections - Relevance: LOW - As Found: Unknown - ID: M26718 - Name: Renal Insufficiency - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M26717 - Name: Renal Insufficiency, Chronic - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007674 - Term: Kidney Diseases - ID: D000007676 - Term: Kidney Failure, Chronic ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M18681 - Name: Endothelial Growth Factors - Relevance: LOW - As Found: Unknown - ID: M11900 - Name: Mitogens - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01065779 **Brief Title:** FOSAMAX PLUS and FOSAMAX PLUS D Re-examination Study (0217A-267) **Official Title:** Re-examination Study for General Drug Use to Assess the Safety and Efficacy Profile of FOSAMAX PLUS and FOSAMAX PLUS D in Usual Practice #### Organization Study ID Info **ID:** 0217A-267 #### Organization **Class:** INDUSTRY **Full Name:** Organon and Co #### Secondary ID Infos **ID:** 2010_007 ### Status Module #### Completion Date **Date:** 2010-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-02-03 **Type:** ACTUAL **Last Update Submit Date:** 2022-02-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-07 **Type:** ACTUAL #### Results First Post Date **Date:** 2011-09-13 **Type:** ESTIMATED **Results First Submit Date:** 2011-06-21 **Results First Submit QC Date:** 2011-08-09 #### Start Date **Date:** 2006-03 **Status Verified Date:** 2022-02 #### Study First Post Date **Date:** 2010-02-09 **Type:** ESTIMATED **Study First Submit Date:** 2010-02-08 **Study First Submit QC Date:** 2010-02-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Organon and Co #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This survey is conducted for preparing application materials for re-examination under the Pharmaceutical Affairs Laws and its Enforcement Regulation, its aim is to reconfirm the clinical usefulness of FOSAMAX PLUS / FOSAMAX PLUS D through collecting the safety information according to the Re-examination Regulation for New Drugs. Note: FOSAMAX PLUS D is known as FOSAMAX PLUS in several markets. FOSAMAX PLUS (70 mg/2800 IU) and FOSAMAX PLUS D (70 mg/5600 IU). ### Conditions Module **Conditions:** - Osteoporosis ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 880 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with Osteoporosis treated with FOSAMAX PLUS (70 mg/2800 IU) or FOSAMAX PLUS D (70 mg/5600 IU). **Intervention Names:** - Drug: FOSAMAX PLUS - Drug: FOSAMAX PLUS D **Label:** FOSAMAX PLUS or FOSAMAX PLUS D ### Interventions #### Intervention 1 **Arm Group Labels:** - FOSAMAX PLUS or FOSAMAX PLUS D **Description:** Patients with Osteoporosis treated with FOSAMAX PLUS (70 mg alendronate/2800 International Units (IU) Vitamin D). One tablet taken once weekly. **Name:** FOSAMAX PLUS **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - FOSAMAX PLUS or FOSAMAX PLUS D **Description:** Patients with Osteoporosis treated with FOSAMAX PLUS D (70 mg alendronate/5600 IU Vitamin D). One tablet taken once weekly. **Name:** FOSAMAX PLUS D **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Number of participants that experienced Serious Adverse events (SAE). There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators. SAEs were considered serious if the event resulted in: * death or was life-threatening * prolonged an existing inpatient hospitalization * a persistent or significant disability/ incapacity * a congenital anomaly/ birth defect * a significant medical situation, other important medical event based upon appropriate medical judgment of the investigator **Measure:** Number of Participants With Serious Adverse Events **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation **Description:** Number of participants that experienced unexpected Adverse Events (AEs) regardless of whether or not the AE was considered related to the use of the product. There was no required routine visit scheduled for AE assessment. An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also considered an AE. **Measure:** Number of Participants With Unexpected Adverse Events **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation **Description:** An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also considered an AE. There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators. **Measure:** Number of Participants With Non-Serious AEs **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation **Description:** Evaluation of disease improvement was conducted in 3 categories of "improved", "unchanged", or "worsened". Changes in biochemical markers and vitamin D levels were reviewed before (baseline) and after treatment using statistical analyses to determine disease status, which was reported as either "improved", "unchanged", or "worsened". **Measure:** Number of Participants With Improved, Unchanged, or Worsened Disease **Time Frame:** Baseline and end of Treatment (Up to ~ 16 weeks) **Description:** For efficacy evaluation, changes in Serum 25-hydroxyvitamin D were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Measure:** Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Description:** For efficacy evaluation, changes in Serum Osteocalcin were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Measure:** Change From Baseline in Serum Osteocalcin at End of Treatment **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Description:** For efficacy evaluation, changes in Serum Deoxypyridinoline were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Measure:** Change From Baseline in Urine Deoxypyridinoline at End of Treatment **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Description:** For efficacy evaluation, changes in Serum Alkaline Phosphatase were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Measure:** Change From Baseline in Alkaline Phosphatase at End of Treatment **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participants who are treated with FOSAMAX PLUS / FOSAMAX PLUS D within label for the first time Exclusion Criteria: * Participants who have a contraindication to FOSAMAX PLUS / FOSAMAX PLUS D according to the current local label **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Merck Sharp & Dohme LLC **Name:** Medical Monitor **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001851 - Term: Bone Diseases, Metabolic - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12947 - Name: Osteoporosis - Relevance: HIGH - As Found: Osteoporosis - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5130 - Name: Bone Diseases, Metabolic - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010024 - Term: Osteoporosis ### Intervention Browse Module - Ancestors - ID: D000050071 - Term: Bone Density Conservation Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M21353 - Name: Alendronate - Relevance: HIGH - As Found: Baclofen - ID: T442 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: T479 - Name: Vitamin D3 - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000019386 - Term: Alendronate ### Misc Info Module #### Removed Countries - Country: Korea, Republic of - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit. #### Event Groups **Group ID:** EG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** EG000 **Other Num at Risk:** 798 **Serious Number At Risk:** 798 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D **Frequency Threshold:** 5 **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 880 **Units:** Participants ### Group **ID:** BG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.05 **Value:** 67.12 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 741 **Class Title:** Female #### Measurement **Group ID:** BG000 **Value:** 57 **Class Title:** Male #### Measurement **Group ID:** BG000 **Value:** 82 **Class Title:** Excluded from Analysis **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** NUMBER **Title:** Sex/Gender, Customized **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** ClinicalTrialsDisclosure@merck.com **Organization:** Merck Sharp & Dohme Corp **Title:** Senior Vice President, Global Clinical Development ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 42 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 549 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 239 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.48 - **Upper Limit:** - **Value:** 1.73 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.32 - **Upper Limit:** - **Value:** 0.69 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.83 - **Upper Limit:** - **Value:** 1.03 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 37.58 - **Upper Limit:** - **Value:** -16.36 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Number of participants that experienced Serious Adverse events (SAE). There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators. SAEs were considered serious if the event resulted in: * death or was life-threatening * prolonged an existing inpatient hospitalization * a persistent or significant disability/ incapacity * a congenital anomaly/ birth defect * a significant medical situation, other important medical event based upon appropriate medical judgment of the investigator **Parameter Type:** NUMBER **Population Description:** Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit. **Reporting Status:** POSTED **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation **Title:** Number of Participants With Serious Adverse Events **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 2 **Description:** Number of participants that experienced unexpected Adverse Events (AEs) regardless of whether or not the AE was considered related to the use of the product. There was no required routine visit scheduled for AE assessment. An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also considered an AE. **Parameter Type:** NUMBER **Population Description:** Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit. **Reporting Status:** POSTED **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation **Title:** Number of Participants With Unexpected Adverse Events **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 3 **Description:** An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also considered an AE. There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators. **Parameter Type:** NUMBER **Population Description:** Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit. **Reporting Status:** POSTED **Time Frame:** Up to ~ 16 weeks and 14 days after treatment discontinuation **Title:** Number of Participants With Non-Serious AEs **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 4 **Description:** Evaluation of disease improvement was conducted in 3 categories of "improved", "unchanged", or "worsened". Changes in biochemical markers and vitamin D levels were reviewed before (baseline) and after treatment using statistical analyses to determine disease status, which was reported as either "improved", "unchanged", or "worsened". **Parameter Type:** NUMBER **Population Description:** Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. **Reporting Status:** POSTED **Time Frame:** Baseline and end of Treatment (Up to ~ 16 weeks) **Title:** Number of Participants With Improved, Unchanged, or Worsened Disease **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 5 **Description:** For efficacy evaluation, changes in Serum 25-hydroxyvitamin D were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included. **Reporting Status:** POSTED **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Title:** Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment **Type:** PRIMARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 6 **Description:** For efficacy evaluation, changes in Serum Osteocalcin were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included. **Reporting Status:** POSTED **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Title:** Change From Baseline in Serum Osteocalcin at End of Treatment **Type:** PRIMARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 7 **Description:** For efficacy evaluation, changes in Serum Deoxypyridinoline were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included. **Reporting Status:** POSTED **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Title:** Change From Baseline in Urine Deoxypyridinoline at End of Treatment **Type:** PRIMARY **Unit of Measure:** nmol/mmol ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Outcome Measure 8 **Description:** For efficacy evaluation, changes in Serum Alkaline Phosphatase were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included. **Reporting Status:** POSTED **Time Frame:** Baseline and End of Treatment (Up to ~ 16 weeks) **Title:** Change From Baseline in Alkaline Phosphatase at End of Treatment **Type:** PRIMARY **Unit of Measure:** mg/dL ##### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** OG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D ### Participant Flow Module #### Group **Description:** Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly. **ID:** FG000 **Title:** FOSAMAX PLUS/ FOSAMAX PLUS D #### Period **Title:** Overall Study ##### Withdraw **Type:** Duplicate Investigation ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Withdraw **Type:** Investigation Before Contract Date ###### Reason **Group ID:** FG000 **Number of Subjects:** 37 ##### Withdraw **Type:** Non-enrollment Period Administration ###### Reason **Group ID:** FG000 **Number of Subjects:** 10 ##### Withdraw **Type:** Not Administered With Study Drug ###### Reason **Group ID:** FG000 **Number of Subjects:** 17 ##### Withdraw **Type:** Failed to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 10 ##### Withdraw **Type:** Inclusion Criteria Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 880 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 798 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 82 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02755779 **Brief Title:** Characterization of Breast Masses Incidentally Detected on Chest CT **Official Title:** Characterization of Breast Masses Incidentally Detected on Chest CT - a Prospective Study #### Organization Study ID Info **ID:** 0067-16-TLV #### Organization **Class:** OTHER **Full Name:** Tel Aviv Medical Center ### Status Module #### Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2016-05-02 **Type:** ESTIMATED **Last Update Submit Date:** 2016-04-28 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Start Date **Date:** 2016-06 **Status Verified Date:** 2016-04 #### Study First Post Date **Date:** 2016-04-29 **Type:** ESTIMATED **Study First Submit Date:** 2016-04-27 **Study First Submit QC Date:** 2016-04-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Tel Aviv Medical Center #### Responsible Party **Investigator Affiliation:** Tel Aviv Medical Center **Investigator Full Name:** Yoav Amitai **Investigator Title:** Dr **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Although Computed tomography (CT) is not routinely used to evaluate beast masses, It is common to discover Incidental breast lesions on chest CT. The goal of this study is to investigate the incidence and appearance of incidentally discovered breast masses on chest CT. ### Conditions Module **Conditions:** - Breast Cancer ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Enrolling 100 patients with breast masses to study **Measure:** Patient enrollment **Time Frame:** One year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Woman with incidentally discovered breast masses on chest CT Exclusion Criteria: * Male gender * Known breast cancer **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Woman over 18 ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** yoavslava@yahoo.com **Name:** Yoav Amitai, Dr **Phone:** +972544771715 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Sourasky medical center Tel aviv **Name:** Yoav Amitai, Dr **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04866979 **Acronym:** StimoLaMente **Brief Title:** Applying Non-invasive Brain Stimulation in Alzheimer's Rehabilitation **Official Title:** StimoLaMente - La Stimolazione Cerebrale Non Invasiva Applicata Alla Riabilitazione Della Malattia di Alzheimer/ StimoLaMente - Applying Non-invasive Brain Stimulation in Alzheimer's Rehabilitation #### Organization Study ID Info **ID:** UStudidiTrento #### Organization **Class:** OTHER **Full Name:** Università degli Studi di Trento ### Status Module #### Completion Date **Date:** 2024-01-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-10 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-09 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-01-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-04-06 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2021-04-30 **Type:** ACTUAL **Study First Submit Date:** 2021-04-06 **Study First Submit QC Date:** 2021-04-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Università degli Studi di Trento #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Presently, few studies have evaluated the clinical impact of rTMS in Alzheimer's disease. Though some studies have demonstrated an improvement, there have been conflicting results, as others do not seem to demonstrate beneficial effects. Furthermore, it is the combined application of rTMS with cognitive training that could represent a real turning point in interventions aiming to slow down cognitive decline resulting from AD. Research has shown that the best way to promote the strengthening of a network is to stimulate the area while simultaneously activating the network (i.e. through cognitive training) which supports the specific function of interest. Recently, there have been new protocols from animal model research showing that "bursts" of repetitive stimulation at a high theta frequency induce synaptic plasticity in a much shorter time period than required by standard rTMS protocols. This type of rTMS stimulation, theta-burst stimulation (TBS), is therefore even more compelling as a therapeutic intervention given that it includes the benefits previously ascribed to other rTMS protocols, but requires less administration time. Furthermore, studies conducted using both types of stimulation suggest that TBS protocols are capable of producing long term effects on cortical excitability that exceed the efficacy of those using standard rTMS protocols. This project offers patients the possibility of accessing an innovative non-invasive, and non-pharmacological treatment. The goal is to evaluate the clinical efficacy TBS in patients diagnosed with mild cognitive decline (MCI) and AD, verifying if TBS in conjunction with cognitive training produces results better than those obtainable with only one of the two methodologies alone. Patients will be evaluated throughout the full scope of the treatment period, through clinical assessments and neuropsychological evaluations. We will examine neuroplastic changes by investigating the neural correlates underlying improvements using the multimodal imaging technique: TMS-EEG co-registration. A secondary objective will be to define the most effective stimulation protocol, verifying if TBS applied continuously (cTBS) or intermittently (iTBS) produces better behavioral outcomes. The results will be crucial to gain a better understanding of the mechanisms through which brain stimulation contributes to the promotion of neuroplasticity, and the efficacy of TBS combined with cognitive training. **Detailed Description:** METHODS AND PROCEDURES The materials and methods of investigation proposed will be the following: * Administration of rTMS in theta burst mode (TBS - intermittent and continuous) * Administration of computerized cognitive training * Administration of a battery of neuropsychological tests * Administration of questionnaires and scales * Recording of the electroencephalogram (EEG) * Combination of EEG recording with single-pulse TMS administration (TMS-EEG) Different TBS stimulation protocols will be applied: 1. Intermittent theta burst stimulation (iTBS): this protocol consists in the administration of 600 pulses divided into blocks of 3 pulses at 50 Hz which are applied at 5 Hz (every 200 ms), alternating 2 s of stimulation with 8 s of pause. 2. Continuous theta burst stimulation (cTBS): this protocol consists in the administration of 600 pulses divided into blocks of 3 pulses at 50 Hz that are applied at 5 Hz (every 200 ms). In both stimulation protocols, the stimulation intensity will be equal to 80% of the motor threshold value at rest. As for the protocols that involve the application of sham/placebo stimulation, the rTMS will be administered by applying to the coil a piece of wood or plastic of about 30 mm in thickness, a distance that ensures that the magnetic pulse does not reach the cortex, and built so as to appear as an integral part of the apparatus. All stimulation parameters adopted in this study are in accordance with the safety guidelines for the application of rTMS. Cognitive rehabilitation protocol For patients assigned to the protocol including the application of cognitive training (TBS + CT; CT), the training will be administered immediately following the application of rTMS (both in the real intermittent or continuous condition, and placebo) and will last 25 minutes. Cognitive training will be administered through dedicated software that uses an individualized adaptive methodology based on the participant's performance. The rehabilitation of memory functions, associated with the stimulation of the left DLPFC, will be focused on learning face-name associations. The face-name association training involves an acquisition phase in which patients are shown faces with an associated name and are asked to memorize these associations. The reproduction phase follows the training phase, in which the patient's task will consist in finding the face that corresponds to the associated name. Based on the patient's performance, the level of difficulty is modulated by increasing or decreasing the number of associations to be memorized and possibly, for higher difficulty levels, by adding other information to be memorized (for example, a profession). Neuropsychological and psychological evaluation All patients will undergo a neuropsychological assessment before the start of treatment (t0), at the end of the intensive treatment phase (t1), at the end of the maintenance phase (t2), and after 3 (t3) and 5 months (t4) from the start of treatment (Figure 1). The evaluation of the patients after some time (follow-up) from the end of the treatment will allow for the verification of long-term effects. A possible "practice effect" resulting from the repeated and quick administration of neuropsychological tests is expected and will be considered in the data analysis, as in all experimental protocols of this type. The practice effect is a factor common to all experimental groups and does not affect the evaluation of the efficacy of the treatment, the primary objective of the study. The EEG will be acquired from 64 sintered Ag / AgCl electrodes placed on the scalp in accordance with the international 10-20 system through an EEG acquisition system compatible with TMS. The EEG signal will be acquired with a high-pass filter at 0.01 Hz, a low-pass filter at 1000 Hz and with a sampling frequency of 5000 Hz. The impedance of the electrodes will be kept below 5 kΩ. The TMS-EEG co-registration will consist in the administration of 120 pulses on the target area stimulated in the application phase of the protocol (right DLPFC or left DLPFC) at an intensity equal to 110% of the motor threshold at rest with a random frequency between 0.2- 0.4 Hz. The analysis of the data recorded by the combination of TMS-EEG will allow an in-depth evaluation of the modulations of cortical activity induced by the different treatment protocols and, in particular, will allow the investigation of cortical excitability and inhibition, connectivity cortico-cortical and the intrinsic ability of the stimulated areas to generate oscillatory activity. This method will be able to provide a unique measure of local cortical activity and effective cortical-cortical connectivity . The characterization and organization of brain networks will be investigated using graph theory. Statistical Analysis: The variables that will be considered for the analysis of clinical, neuropsychological and neurophysiological data are: a) treatment effect over time (t0, t1, t2, t3, t4); b) type of treatment protocol (combination of TBS and cognitive training, isolated application of TBS, isolated application of cognitive training); c) type of stimulation protocol (cTBS, iTBS) and d) clinical group (AD or MCI). The experimental design will be both "within subjects" within each variable of interest (for example, investigating the difference between t1 and baseline to evaluate the effect of intensive treatment), and "between subjects" regarding the data between the different treatment protocols (for example, investigating the difference between combination of TBS and cognitive training and isolated application of TBS, to evaluate which protocol produces the greatest benefits), between different stimulation protocols (for example, investigating the difference between cTBS and iTBS to evaluate which protocol produces greater benefits) and between clinical conditions (to assess whether the same treatment leads to differences in the achieved benefit between the two groups of patients, AD and MCI). Calculation of sample size: The primary outcome for the calculation of the sample size was defined as the effect of the cTBS protocol and the iTBS protocol (both in combination with cognitive training) compared to the treatment involving the combination of cognitive training with TBS placebo, and the one which involves only the TBS protocols applied in isolation, on the MMSE score achieved at the end of the treatment. Based on the results of a previous rTMS study on a sample of AD patients (Ahmed et al. 2012), we estimate that at the end of our treatment there will be an improvement in the MMSE score of at least 3 points (SD of change = 2.95) for protocols that involve the combination of cognitive training and real TBS, and of 0.2 points (SD of change = 2.7) for the treatment that involves the combination of cognitive training and placebo TBS.Considering an alpha value of 0.05 and a power of 0.80, we estimate that the number of patients to be recruited should be 16 patients per group, increased to 20 per group to take into account a possible dropout rate of 20%. Techniques provided for data processing Behavioral and neurophysiological data will be analyzed by analysis of variance (ANOVA) and post-hoc comparisons (t-test, contrast analysis). Statistical processing software Data processing will be performed with BrainVision Analyzer, SPSS and/or Statistica software. Ethical Considerations and Assessment of the Risk/Benefit Ratio: Expected benefits Based on the assumptions of the present project, patients who will receive the treatment that involves the combined application of rTMS and cognitive training should show a clinical response, based on the primary endpoints reported above, better than the patients assigned to the protocols in which rTMS and cognitive training are applied in isolation. The research also provides indirect scientific / cognitive benefits, in terms of advancing knowledge on the development of treatments with proven efficacy and on the mechanisms underlying Alzheimer's dementia. Potential Risks: The risks are represented by the use of electro-medical equipment, however, all of which have EC authorization for use with patients. For this protocol, all appropriate safety measures will be put in place for studies with brain stimulation as indicated by the international scientific community. Although, following the international guidelines for the safe administration of TMS no adverse events are expected, it should be noted that the environment in which the research will take place and the personnel involved are able to cope with any side effects of stimulation. The stimulation parameters chosen take into account the clinical goals and safety of the participants. With regard to EEG procedures, redness of the skin immediately under the electrodes is possible, following abrasion from the application of the electroconductive gel. All the procedures foreseen by the research will be carried out paying particular attention to the patient involved, adopting all the necessary measures so that no critical issues related to stress or fatigue arise. Risk/Benefit Ratio: It is believed that in the proposed study program, the risk/benefit ratio is in favor of benefit, in terms of increased knowledge and expected direct benefit for the participants. According to the classification of a consensus paper, this protocol is part of class 2 studies, which identify studies with indirect benefits and moderate risks: these are studies with patients where the clinical benefit is speculative, but from which important data could come for the development of effective treatments. Ethical Considerations: At the end of the study, patients will not be informed of the treatment protocol to which they have been assigned but will be informed about the overall results of the study, receiving a report containing a summary of the results achieved by the project. Informed Consent: Participation in the study is on a voluntary basis: each subject will obtain explicit information regarding the nature of the project and will have to sign a written consent before they can be included. Participants can withdraw their consent to participate at any time, without any consequences. Data storage and processing: The data will be protected and anonymized according to the procedures in force. All data regarding identification will be encrypted within the database and the subjects will be identified only with a code. However, the nature of the study makes it necessary to preserve the data regarding the identification of the participants because the project provides for follow-up evaluations. Access to the database containing the collected data and the results will be restricted to the researchers involved with the project. Sensitive data and all paper data will be kept under lock and key at the various facilities. The research manager will also be responsible for the appropriate conservation of these data. As this study involves experimental data, the experimental data will later be published and shared with national and international scientific communities. ### Conditions Module **Conditions:** - Alzheimer Disease - Mild Cognitive Impairment **Keywords:** - Transcranial Magnetic Stimulation - Theta Burst Stimulation - Alzheimer Disease - Mild Cognitive Impairment - Memory - TMS-EEG - Electroencephelography ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL **Intervention Model Description:** 200 total patients:100 AD patients,100 MCI patients. Random assignment to 1 of 5 protocols (20 AD patients and 20 MCI patients per protocol). Patients will be balanced using MMSE and age matching to create homogeneous groups. Protocols: 1. Combination of continuous TBS plus cognitive training (cTBS + CT); 2. Combination of intermittent TBS plus cognitive training (iTBS + CT); 3. Continuous TBS only (cTBS); 4. intermittent TBS only (iTBS); 5. Cognitive training only (with placebo TBS) (CT). 2 main treatment phases; 1) intensive phase (2 weeks, applied daily 5 times a week, 10 sessions); 2) maintenance phase, (5 weeks, 2 times a week, 10 sessions). Patients will undergo a clinical, neuropsychological, and neurophysiological evaluation before the start of treatment (baseline, t0=Week1), at the end of the intensive phase (t1= Week 4), at the end of the maintenance phase (t2 = Week 8), and after 3 (t3 = Week 12) and 5 months (t4 = Week 20) from the start of treatment. ##### Masking Info **Masking:** TRIPLE **Masking Description:** We will implement a randomized, non-pharmacological study, with a double-blind certified medical device (neither the patient nor the clinician / researcher who will carry out the evaluations will be aware of the group to which the patient has been assigned). **Who Masked:** - PARTICIPANT - CARE_PROVIDER - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Continuous mode of TBS applied in conjunction with cognitive training that will commence directly after the stimulation protocol has been completed. **Intervention Names:** - Device: Experimental: Continuous TBS (cTBS) - Behavioral: Cognitive training (CT). **Label:** Combination of continuous TBS plus cognitive training (cTBS + CT) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Intermittent mode of TBS applied in conjunction with cognitive training that will commence directly after the stimulation protocol has been completed. **Intervention Names:** - Device: Intermittent TBS (iTBS) - Behavioral: Cognitive training (CT). **Label:** Combination of intermittent TBS plus cognitive training (iTBS + CT) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** TBS in continuous mode application, only (without cognitive training). **Intervention Names:** - Device: Experimental: Continuous TBS (cTBS) **Label:** Continuous TBS only (cTBS) **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** TBS in intermittent mode application, only (without cognitive training). **Intervention Names:** - Device: Intermittent TBS (iTBS) **Label:** Intermittent TBS only (iTBS) **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** TBS Sham will be implemented using the same set-up as a true TBS protocol but with "sham stimulation". Directly following sham stimulation (as in the true combination of stimulation + cognitive training protocols), patients will undergo 25 minutes of cognitive training. **Intervention Names:** - Behavioral: Cognitive training (CT). - Device: Sham Stimulation (shamTBS) **Label:** Cognitive training only (with sham TBS) (CT). **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Combination of continuous TBS plus cognitive training (cTBS + CT) - Continuous TBS only (cTBS) **Description:** Application of cTBS. cTBS will be applied to the left dorsolateral prefrontal cortex (left DLPFC). The coil will be placed at the EEG 10-20 International System position of the F3 electrode. Stimulation parameters will be TBS delivery of 600 pulses divided into blocks of 3 pulses at 50 Hz, which are applied at 5 Hz (every 200 ms), with a stimulation intensity equal to 80% of the motor threshold value at rest. **Name:** Experimental: Continuous TBS (cTBS) **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Combination of intermittent TBS plus cognitive training (iTBS + CT) - Intermittent TBS only (iTBS) **Description:** Application of iTBS. iTBS will be applied to the left dorsolateral prefrontal cortex (left DLPFC). The coil will be placed at the EEG 10-20 International System position of the F3 electrode. Stimulation parameters will be TBS delivery of of 600 pulses divided into blocks of 3 pulses at 50 Hz, which are applied at 5 Hz (every 200 ms), alternating 2 seconds of stimulation with a pause of 8 seconds, with a stimulation intensity equal to 80% of the motor threshold value at rest. **Name:** Intermittent TBS (iTBS) **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Cognitive training only (with sham TBS) (CT). - Combination of continuous TBS plus cognitive training (cTBS + CT) - Combination of intermittent TBS plus cognitive training (iTBS + CT) **Description:** Cognitive training (memory rehabilitation via RehaCom computer software) of 25 min. The training will be focused on memory rehabilitation, implementing a face-name association paradigm. The software uses an individualized adaptive methodology based on the participant's performance. **Name:** Cognitive training (CT). **Type:** BEHAVIORAL #### Intervention 4 **Arm Group Labels:** - Cognitive training only (with sham TBS) (CT). **Description:** Sham rTMS (TBS) will be administered by applying a 30mm thick piece of wood or plastic to a real TMS coil during "stimulation", and this additional element will be constructed in such a way that it appears to be an integral part of the apparatus such that the patient remains unaware that they are not receiving stimulation (Rossi et al., 2007 ).This 30mm distance is adequate to ensure that the magnetic pulse does not reach the cortex. **Name:** Sham Stimulation (shamTBS) **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Mean change in performance in ability to correctly memorize face/name paired associations \[score range min=7, max=n/a, higher score=better outcome\]. Patients will start at level 7, the level at which the training software begins paired face/name associations. The software will not allow the patient to go below level 7, so this is the minimum score (level) threshold for all patients. **Measure:** Face-name associative memory performance - Measure of Memory Recall **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Neuropsychological evaluation using mean changes in the Mini-Mental State Evaluation(MMSE) score Score range is from 0-30, with a score of 25 or higher is classed as "normal". If the score is below 25, the result indicates a possible cognitive impairment. A lower score = worse outcome **Measure:** Mini-Mental State Evaluation (MMSE) Score - Non-Trained Measure of Global Function **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) #### Secondary Outcomes **Description:** 120 pulses will be delivered to the target area (right DLPFC or left DLPFC) at 110% resting motor threshold intensity during EEG registration. This outcome will analyze cortical excitability and inhibition changes induced in the state of excitability/inhibition of brain circuits following the TMS impulse. The amplitude will be used as a marker of cortical excitability. **Measure:** TMS evoked potentials - TEP: Analysis of cortical excitability and inhibition changes induced in the state of excitability/inhibition of brain circuits following the TMS impulse. **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** 120 pulses will be delivered to the target area (right DLPFC or left DLPFC) at 110% resting motor threshold intensity during EEG registration. This outcome will analyze changes in the latencies and topographical distribution of the TEPs thus providing a connectivity index. This connectivity index will be used to infer the propagation of the activity from the stimulation site to functionally connected areas. **Measure:** Connectivity Index - Connectivity evoked by TMS: cortico-cortical connectivity analysis **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** 120 pulses will be delivered to the target area (right DLPFC or left DLPFC) at 110% resting motor threshold intensity during EEG registration. This outcome will analyze changes in responses induced by TMS in the frequency domain for the intrinsic capacity of the stimulated area to generate oscillatory activity in specific frequency bands. **Measure:** TMS evoked oscillations: changes induced by TMS and its influence on intrinsic oscillatory activity **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes in test scores \[score range 0-36, higher score=better outcome\]) **Measure:** Raven's Colored Progressive Matrices: Evaluation of abstract non-verbal reasoning **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes in test scores \[score range 0-9, higher score=better outcome\] **Measure:** Digit Span: Evaluation of short and long term memory (verbal) **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes in test scores \[score range 0-10, higher score=better outcome\] **Measure:** Spatial Span: Evaluation of short and long term memory (visuospatial) **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes in test scores \[score range 0-28, higher score=better outcome\]; **Measure:** Prose Memory:Evaluation of short and long term memory **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on tests scores \[Immediate: score range 0-36; Deferred: score range 0-12, higher score=better outcome\] **Measure:** Free And Cued Selective Reminding Test: Evaluation of short and long term memory **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on tests scores \[score range 0-36, higher score=better outcome\] **Measure:** Deferred re-enactment of the Complex Figure by Rey Osterrieth: Long term memory evaluation **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on tests scores \[score range 0-36, higher score = better outcome\] **Measure:** Token Test: Evaluation of linguistic production **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on tests scores: \[score range 0-no limits, higher score=better outcome\] **Measure:** Semantic fluency and Phonemic fluency **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes in scores on MFCT Time \[score range, min= N/A, max= no limit, higher score=worse outcome; Mean changes in scores on MFCT Accuracy \[score range min=0, max=20, higher score=better outcome\]; Mean changes in scores on MFCT False alarm \[score range min: N/A, max= no limit, high score=worse outcome\] **Measure:** Multiple Features Cancellation task: Evaluation of attention and executive function "MFCT" **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores for each condition \[score range: min= n/a, max= no limits, higher score=worse outcome\] **Measure:** Trail Making test (for A, B and B-A conditions): Evaluation of attention and executive function **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score ranges min=N/A, max= no limit, higher score=worse outcome\] **Measure:** Stroop test Error and Time: Evaluation of attention and executive function **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score range 0-60, higher score=better outcome\] **Measure:** Attentional Matrices: Evaluation of attention and executive function **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score range 0-36, higher score=better outcome\] **Measure:** Copy of Rey's Complex Figure: Evaluation of practical and visual-constructive skills **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score range 0-30, higher score=worse outcome\] **Measure:** Geriatric Depression Scale, GDS:Evaluation of depressive symptoms in the elderly **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score range 0-52, higher score=worse outcome\] **Measure:** Questionnaire of Identification of Deficits (QID): Evaluation on quality of life and identification of deficit questionnaire for the patient and caregiver **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score range 0-8, higher score=worse outcome\] **Measure:** Clinical Insight Rating Scale, (CIRS): Evaluation of awareness of deficits and disease **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) **Description:** Mean changes on scores \[score range 0-35, higher score=better outcome\] **Measure:** Jefferson Scale: Evaluation of the patient's perception of empathy **Time Frame:** Prior to treatment (baseline=t0=week 1), at the end of the intensive treatment phase (t1=Week 4), at the end of the maintenance phase (t2=Week 8), 3 months post-treatment (t3=Week 12), & 5 months post treatment (t4=Week 20) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: General Inclusion Criteria (must be met for both AD and MCI group): * right-handed * normal or corrected to normal vision through lenses * meet inclusion criteria related to TMS * Be able to provide information regarding their cognitive and functional skills, or have a caregiver available who is able to provide the patient information necessary for participation in the study and who is present when signing the patient's informed consent. AD Patient Inclusion Criteria: * Mini Mental State Examination (MMSE) score ≥ 16; * Stable intake of cholinesterase inhibitors for at least 3 months before the start of the protocol MCI Patient Inclusion Criteria: * Diagnosis of mild cognitive impairment * Mini Mental State Examination (MMSE) score ≥ 24; Patients will be selected through clinical evaluation (battery of neuropsychological tests at the Neurocognitive Rehabilitation Center (CeRiN) and, in accordance with the APSS, a CSF and PET examination will be performed as well as a further finalized neuropsychological evaluation for research. Exclusion Criteria: * Patients who are unable to perform the tasks required by the experimental procedure; * History and / or evidence of any other central nervous system disorder that could be interpreted as a cause of dementia such as structural or developmental abnormality, epilepsy, infectious disease, degenerative or inflammatory/demyelinating diseases of the central nervous system such as Parkinson's disease or Fronto-temporal dementia * History of significant psychiatric disease which, in the investigator's judgment, could interfere with study participation * History of alcohol or other substance abuse, according to DSM-V criteria, or recent or previous history of drug abuse if this could be a contributing factor to dementia * Ongoing treatments with drugs that contain / intake of the following substances: imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, (MDMA, ecstasy), phencyclidine (PCP, angel dust), gamma-hydroxybutyrate acid (GHB), theophylline * Presence of cardiac pacemakers, electronic prostheses, bio-stimulators, metal inserts or electrodes implanted in the brain or skull or spine. Absolute exclusion criteria (Criteria for TMS), which in detail are: * presence of cardiac pace-makers, artificial heart valves and / or bio-stimulators * presence of hearing aids located in the middle ear; * presence of metal inserts on the head and shoulders; **Maximum Age:** 85 Years **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** carlo.miniussi@unitn.it **Name:** Carlo Miniussi, PhD **Phone:** 0464 808694 **Role:** CONTACT #### Locations **Location 1:** **City:** Rovereto **Contacts:** ***Contact 1:*** - **Email:** alessandra.dodich@unitn.it - **Name:** Alessandra Dodich - **Phone:** 0464 808162 - **Role:** CONTACT **Country:** Italy **Facility:** Centro Interdipartimentale Mente/Cervello - CIMeC **State:** Trento **Status:** RECRUITING **Zip:** 38068 #### Overall Officials **Official 1:** **Affiliation:** Università degli Studi di Trento **Name:** Carlo Miniussi, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** The data will be shared with Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose, for research purposes only. The only data will be shared will be those which aid in achieving the research aims of the approved proposal, previously approved by the above mentioned independent ethical review committee. Proposals for data sharing should be directed to carlo.miniussi@unitn.it following ethical committee approval. To gain access, data requestors will need to sign a data access agreement. The sharing of the data will be contingent on the above-mentioned criteria, namely, the approval of an independent ethics committee and the relevance of the requested data as it pertains to the research question. **Description:** Individual participant data be available (including data dictionaries) after de-identification. The data in particular that will be shared are individual participant data that underlie the results reported in the published article, after de-identification (text, tables, figures, and appendices). **Info Types:** - STUDY_PROTOCOL **IPD Sharing:** YES **Time Frame:** The data will be available immediately following article publication, and the time frame for sharing this data will have no foreseen end-date. ### References Module #### References **Citation:** Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14. **PMID:** 21671144 **Citation:** Alcala-Lozano R, Morelos-Santana E, Cortes-Sotres JF, Garza-Villarreal EA, Sosa-Ortiz AL, Gonzalez-Olvera JJ. 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J Exp Neurosci. 2015 Jun 3;9:43-51. doi: 10.4137/JEN.S24004. eCollection 2015. **PMID:** 26064066 **Citation:** Stam CJ, Jones BF, Nolte G, Breakspear M, Scheltens P. Small-world networks and functional connectivity in Alzheimer's disease. Cereb Cortex. 2007 Jan;17(1):92-9. doi: 10.1093/cercor/bhj127. Epub 2006 Feb 1. **PMID:** 16452642 **Citation:** Zhao J, Li Z, Cong Y, Zhang J, Tan M, Zhang H, Geng N, Li M, Yu W, Shan P. Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer's disease patients. Oncotarget. 2017 May 16;8(20):33864-33871. doi: 10.18632/oncotarget.13060. **PMID:** 27823981 ## Document Section ### Large Document Module #### Large Docs - Date: 2020-03-19 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 735982 - Type Abbrev: Prot - Upload Date: 2021-04-23T11:16 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003704 - Term: Dementia - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000024801 - Term: Tauopathies - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000003072 - Term: Cognition Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M29705 - Name: Cognitive Dysfunction - Relevance: HIGH - As Found: Mild Cognitive Impairment - ID: M3885 - Name: Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease - ID: M6904 - Name: Dementia - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M23002 - Name: Tauopathies - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M6301 - Name: Cognition Disorders - Relevance: LOW - As Found: Unknown - ID: T2192 - Name: Familial Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease ### Condition Browse Module - Meshes - ID: D000000544 - Term: Alzheimer Disease - ID: D000060825 - Term: Cognitive Dysfunction ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02090179 **Brief Title:** Evaluation of Blood Brain Barrier Integrity and Structural Abnormalities in MPS IIIB Patients Using Multimodal Magnetic Resonance Imaging **Official Title:** Evaluation of Blood Brain Barrier Integrity and Relationship to Structural Brain Abnormalities in MPS IIIB Patients Using Cerebrospinal Fluid/Serum Albumin Index (CSF-AI) and Multimodal Magnetic Resonance Imaging #### Organization Study ID Info **ID:** NGLU-CL01 #### Organization **Class:** INDUSTRY **Full Name:** Alexion Pharmaceuticals, Inc. #### Secondary ID Infos **ID:** 2013-001938-18 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2014-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-06-27 **Type:** ESTIMATED **Last Update Submit Date:** 2016-06-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-05 **Type:** ACTUAL #### Start Date **Date:** 2013-12 **Status Verified Date:** 2016-06 #### Study First Post Date **Date:** 2014-03-18 **Type:** ESTIMATED **Study First Submit Date:** 2014-03-12 **Study First Submit QC Date:** 2014-03-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Alexion Pharmaceuticals, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of the study is to characterize structural abnormalities in the brain and the integrity of the blood brain barrier in patients with mucopolysaccharidosis type IIIB (MPS IIIB). ### Conditions Module **Conditions:** - MPS IIIB (Sanfilippo B Syndrome) **Keywords:** - MPS IIIB - Mucopolysaccharidosis - Mucopolysaccharidosis type IIIB - Sanfilippo Syndrome - Metabolism, Inborn Errors - Metabolic Diseases - Genetic Diseases, Inborn ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 5 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Those with a definitive diagnosis of MPS IIIB (Sanfilippo B Syndrome). **Label:** MPS IIIB ### Outcomes Module #### Primary Outcomes **Description:** Blood Brain Barrier integrity in MPS IIIB subjects by estimating the CSF-AI. **Measure:** Blood Brain Barrier integrity in MPS IIIB subjects **Time Frame:** Day 0 **Description:** The Blood Brain Barrier transfer coefficient will be measured by DCE-MRI in MPS IIIB subjects. **Measure:** Blood Brain Barrier transfer coefficient **Time Frame:** Day 0 #### Secondary Outcomes **Description:** Structural brain abnormalities in MPS IIIB using imaging and biomarkers related to underlying disease biology of MPS IIIB subjects **Measure:** Structural brain abnormalities in MPS IIIB **Time Frame:** Day 0 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject and/or subject's parent or legal guardian provides informed consent * Subject is ≥5 years of age. * Subject has a definitive diagnosis of MPS IIIB, as determined by either a documented deficiency in alpha-N-acetylglucosaminidase (NAGLU) enzyme activity or documented functionally-relevant mutations in both alleles of the NAGLU gene. Exclusion Criteria: * The subject has any internal or non-removable external metal items that may present a safety risk (for MRI), or any other medical condition or circumstance in which an MRI is contraindicated. * The subject has a known or suspected hypersensitivity to anaesthesia, a bleeding disorder, or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated. * Previous allergic reaction to gadolinium-based MRI contrast media. **Minimum Age:** 5 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Up to six subjects with MPS IIIB. An attempt will be made to enroll equal numbers (three) of MPS IIIB subjects with a classic (severe) disease presentation, and MPS IIIB subjects with an attenuated phenotype. ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United Kingdom ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009083 - Term: Mucopolysaccharidoses - ID: D000002239 - Term: Carbohydrate Metabolism, Inborn Errors - ID: D000008661 - Term: Metabolism, Inborn Errors - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000016464 - Term: Lysosomal Storage Diseases - ID: D000017520 - Term: Mucinoses - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M12041 - Name: Mucopolysaccharidoses - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M11641 - Name: Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M12042 - Name: Mucopolysaccharidosis III - Relevance: HIGH - As Found: MPS IIIB - ID: M5498 - Name: Carbohydrate Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M18871 - Name: Lysosomal Storage Diseases - Relevance: LOW - As Found: Unknown - ID: M19781 - Name: Mucinoses - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: T3901 - Name: Mucopolysaccharidosis - Relevance: LOW - As Found: Unknown - ID: T3904 - Name: Mucopolysaccharidosis Type III - Relevance: LOW - As Found: Unknown - ID: T3906 - Name: Mucopolysaccharidosis Type IIIB - Relevance: HIGH - As Found: MPS IIIB ### Condition Browse Module - Meshes - ID: D000009084 - Term: Mucopolysaccharidosis III ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00300079 **Brief Title:** Study of the Intraocular Pressure (IOP)-Lowering Efficacy of Azopt 1.0% Compared to Timolol 0.5% in Patients With Glaucoma or Ocular Hypertension **Official Title:** A Multiple-Dose Study of the IOP-Lowering Efficacy of Azopt 1.0% Compared to Timolol 0.5% When Added to a PGA as Adjunctive Therapy Over a 24 Hour Period in Patients With Glaucoma or Ocular Hypertension #### Organization Study ID Info **ID:** CM-05-13 #### Organization **Class:** INDUSTRY **Full Name:** Alcon Research #### Secondary ID Infos **ID:** CM-05-13 ### Status Module #### Completion Date **Date:** 2007-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-11-18 **Type:** ESTIMATED **Last Update Submit Date:** 2016-11-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-09 **Type:** ACTUAL #### Start Date **Date:** 2006-09 **Status Verified Date:** 2008-06 #### Study First Post Date **Date:** 2006-03-08 **Type:** ESTIMATED **Study First Submit Date:** 2006-03-06 **Study First Submit QC Date:** 2006-03-06 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of California, San Diego #### Lead Sponsor **Class:** INDUSTRY **Name:** Alcon Research #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This is a multiple-dose study of the IOP-lowering efficacy of Azopt (brinzolamide) 1.0% compared to timolol 0.5% when added to a prostaglandin analogue (PGA) as adjunctive therapy over a 24 hour period in patients with glaucoma or ocular hypertension. ### Conditions Module **Conditions:** - Primary Open Angle Glaucoma - Ocular Hypertension **Keywords:** - Ocular Hypertension Patients ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** brinzolamide 1.0% **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** IOP-lowering at 8 and 16 weeks #### Secondary Outcomes **Measure:** Safety throughout the 16 weeks of the study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Primary open angle glaucoma or ocular hypertension patients Exclusion Criteria: * Women of childbearing potential * History of bronchial asthma, or severe chronic obstructive pulmonary disease * Presence of acute glaucoma **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Diego **Country:** United States **State:** California #### Overall Officials **Official 1:** **Affiliation:** University of California, San Diego **Name:** John Liu, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Liu JH, Medeiros FA, Slight JR, Weinreb RN. Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving latanoprost monotherapy. Ophthalmology. 2009 Mar;116(3):449-54. doi: 10.1016/j.ophtha.2008.09.054. Epub 2009 Jan 20. **PMID:** 19157559 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M9013 - Name: Glaucoma - Relevance: HIGH - As Found: Glaucoma - ID: M9014 - Name: Glaucoma, Open-Angle - Relevance: HIGH - As Found: Primary Open Angle Glaucoma - ID: M12731 - Name: Ocular Hypertension - Relevance: HIGH - As Found: Ocular Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005901 - Term: Glaucoma - ID: D000005902 - Term: Glaucoma, Open-Angle - ID: D000009798 - Term: Ocular Hypertension - ID: D000006973 - Term: Hypertension ### Intervention Browse Module - Ancestors - ID: D000002257 - Term: Carbonic Anhydrase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: AnAg - Name: Antihypertensive Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16757 - Name: Timolol - Relevance: LOW - As Found: Unknown - ID: M242996 - Name: Brinzolamide - Relevance: HIGH - As Found: Tri- - ID: M5515 - Name: Carbonic Anhydrase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000111827 - Term: Brinzolamide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00862979 **Acronym:** MANDELA **Brief Title:** A Study Investigating the Renal Tolerability, Efficacy, and Safety of a CNI-free Versus a Standard Regimen in de Novo Heart Transplant (HTx) Recipients **Official Title:** A Multi-center, Randomized, Open-label, Parallel Group Study Investigating the Renal Tolerability, Efficacy and Safety of a CNI-free Regimen (Everolimus and MPA) Versus a CNI-regimen With Everolimus in Heart Transplant Recipients #### Organization Study ID Info **ID:** CRAD001ADE14 #### Organization **Class:** INDUSTRY **Full Name:** Novartis #### Secondary ID Infos **ID:** 2007-002671-14 ### Status Module #### Completion Date **Date:** 2017-03-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-08-07 **Type:** ACTUAL **Last Update Submit Date:** 2018-07-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-03-06 **Type:** ACTUAL #### Results First Post Date **Date:** 2018-06-25 **Type:** ACTUAL **Results First Submit Date:** 2018-03-05 **Results First Submit QC Date:** 2018-05-23 #### Start Date **Date:** 2009-02-24 **Type:** ACTUAL **Status Verified Date:** 2018-07 #### Study First Post Date **Date:** 2009-03-17 **Type:** ESTIMATED **Study First Submit Date:** 2009-03-16 **Study First Submit QC Date:** 2009-03-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novartis Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study will assess whether a calcineurin inhibitor (CNI)-free regimen with everolimus and mycophenolic acid is associated with a better renal outcome as compared to the standard regimen containing cyclosporine A (which belongs to the class of CNIs) and everolimus; while both treatments are expected to be comparable with respect to efficacy. **Detailed Description:** This study will assess whether a calcineurin inhibitor (CNI)-free regimen with everolimus and mycophenolic acid is associated with a better renal outcome as compared to the standard regimen containing cyclosporine A (which belongs to the class of CNIs) and everolimus; while both treatments are expected to be comparable with respect to efficacy. ### Conditions Module **Conditions:** - Heart Transplantation **Keywords:** - Heart Transplantation - Cardiac Transplantation - CNI-sparing - renal function - CNI - Cyclosporine A - Everolimus - mycophenolic acid ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 162 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **Intervention Names:** - Drug: Everolimus (EVR) - Drug: cyclosporine A (CyA) - Drug: tacrolimus (TAC) - Drug: Corticosteroids **Label:** CNI-regimen **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **Intervention Names:** - Drug: Everolimus (EVR) - Drug: cyclosporine A (CyA) - Drug: tacrolimus (TAC) - Drug: Enteric coated mycophenolate sodium (EC-MPS) - Drug: mycophenolate mofetil (MMF) - Drug: Corticosteroids **Label:** CNI-free-regimen **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - CNI-free-regimen - CNI-regimen **Description:** Everolimus 0.25mg, 0.75mg or 1.0mg based on blood levels (5-10 ng/mL) **Name:** Everolimus (EVR) **Other Names:** - Certican, RAD001 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - CNI-free-regimen - CNI-regimen **Description:** 10 mg, 25 mg, 50 mg or 100 mg capsule according to blood levels for CNI-regimen group. For CNI-free-regimen dispense on month 6 to 9 only **Name:** cyclosporine A (CyA) **Other Names:** - Sandimmun Optoral **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - CNI-free-regimen - CNI-regimen **Description:** 0.5 mg, 1 mg, or 5 mg capsule given according to blood levels for CNI-regimen. For CNI-free-regimen give on month 6 to 9 only **Name:** tacrolimus (TAC) **Other Names:** - Prograf **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - CNI-free-regimen **Description:** 180 mg or 360 mg tablet dosed 1440-2280 mg per day **Name:** Enteric coated mycophenolate sodium (EC-MPS) **Other Names:** - Myfortic **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - CNI-free-regimen **Description:** 250 mg or 500 mg tablets with a dose of 1500-3000 mg per day **Name:** mycophenolate mofetil (MMF) **Other Names:** - CellCept **Type:** DRUG #### Intervention 6 **Arm Group Labels:** - CNI-free-regimen - CNI-regimen **Description:** according to local standard: 0.05-0.3 mg/kg of prednisolone or equivalent **Name:** Corticosteroids **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 cGFR (in mL/min/1.73 m2) = 186.3\*(C-1.154)\*(A-0.203)\*G\*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1. **Measure:** Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 **Time Frame:** Month 18 #### Secondary Outcomes **Description:** Treatment failure was defined as composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade ≥ 3A resp. ISHLT 2004 grade ≥ 2R, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present). If participant had an occurrence in each period it was counted for each period. **Measure:** Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18 **Time Frame:** Month 6 to Month 9; Month 9 to Month 18 **Description:** Major cardiac events (MACE) was defined as one of the following: any death, myocardial infarction, coronary artery bypass grafting **Measure:** Occurrence of Major Cardiac Events (MACE) From Month 6 to 18 **Time Frame:** Month 6 to Month 18 **Description:** Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 12 and 18. For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl) **Measure:** Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18 **Time Frame:** Month 12 and 18 **Description:** Serum Creatinine is an indicator of renal function measured in the blood **Measure:** Serum Creatinine at Month 6, 8, 9, 10 12 and 18 **Time Frame:** Month 6, 8, 9, 10 12 and 18 **Description:** Reciprocal Creatinine Slope is an indication of renal function over time with a higher slope value indicating an improvement in renal function. **Measure:** Reciprocal Creatinine Slope Between Month 6 and Month 18 **Time Frame:** Between Month 6 and Month 18 ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * Heart transplantation, 3 months prior to enrollment * Patients have to receive an immunosuppressive regimen with Sandimmun® Optoral, Certican® and corticosteroids * Sufficient graft function * Sufficient renal function * Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at baseline, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility Exclusion criteria: * Multi-organ recipients, re-transplantation, or previous transplant with any other organ. * Patients who are recipients of A-B-O incompatible transplants * Cold ischemia time \>6 hours * Historical or current peak PRA of \> 25% at time of transplantation * Already existing antibodies against the HLA-type of the receiving transplant Other protocol-defined inclusion/exclusion criteria may apply **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bad Oeynhausen **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 32545 **Location 2:** **City:** Berlin **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 13353 **Location 3:** **City:** Hamburg **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 20246 **Location 4:** **City:** Hannover **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 30625 **Location 5:** **City:** Heidelberg **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 69120 **Location 6:** **City:** Leipzig **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 04289 **Location 7:** **City:** Muenster **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 48149 **Location 8:** **City:** München **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 81377 **Location 9:** **City:** Regensburg **Country:** Germany **Facility:** Novartis Investigative Site **Zip:** 93053 #### Overall Officials **Official 1:** **Affiliation:** Novartis Pharmaceuticals **Name:** Novartis Pharmaceuticals **Role:** STUDY_DIRECTOR ## Document Section ### Large Document Module #### Large Docs - Date: 2016-01-19 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 590341 - Type Abbrev: Prot - Upload Date: 2018-03-05T10:27 - Date: 2017-06-02 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 380010 - Type Abbrev: SAP - Upload Date: 2018-03-05T10:27 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000065095 - Term: Calcineurin Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000935 - Term: Antifungal Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000003879 - Term: Dermatologic Agents - ID: D000018501 - Term: Antirheumatic Agents - ID: D000091203 - Term: MTOR Inhibitors - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000903 - Term: Antibiotics, Antineoplastic - ID: D000000904 - Term: Antibiotics, Antitubercular - ID: D000000995 - Term: Antitubercular Agents - ID: D000000900 - Term: Anti-Bacterial Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: NeuroAg - Name: Neuroprotective Agents - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M255 - Name: Everolimus - Relevance: HIGH - As Found: Head - ID: M18961 - Name: Cyclosporine - Relevance: HIGH - As Found: New - ID: M6730 - Name: Cyclosporins - Relevance: HIGH - As Found: New - ID: M14120 - Name: Prednisolone - Relevance: LOW - As Found: Unknown - ID: M16975 - Name: Triamcinolone Acetonide - Relevance: LOW - As Found: Unknown - ID: M16974 - Name: Triamcinolone - Relevance: LOW - As Found: Unknown - ID: M237966 - Name: Triamcinolone hexacetonide - Relevance: LOW - As Found: Unknown - ID: M209573 - Name: Triamcinolone diacetate - Relevance: LOW - As Found: Unknown - ID: M12128 - Name: Mycophenolic Acid - Relevance: HIGH - As Found: Phase 2 - ID: M18950 - Name: Tacrolimus - Relevance: HIGH - As Found: 3 weeks - ID: M11749 - Name: Methylprednisolone - Relevance: LOW - As Found: Unknown - ID: M1833 - Name: Methylprednisolone Acetate - Relevance: LOW - As Found: Unknown - ID: M11750 - Name: Methylprednisolone Hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M229449 - Name: Prednisolone acetate - Relevance: LOW - As Found: Unknown - ID: M211887 - Name: Prednisolone hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M248881 - Name: Prednisolone phosphate - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M30452 - Name: Calcineurin Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M6252 - Name: Clotrimazole - Relevance: LOW - As Found: Unknown - ID: M11796 - Name: Miconazole - Relevance: LOW - As Found: Unknown - ID: M4254 - Name: Antifungal Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M7074 - Name: Dermatologic Agents - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M21960 - Name: Sirolimus - Relevance: LOW - As Found: Unknown - ID: M353695 - Name: Temsirolimus - Relevance: LOW - As Found: Unknown - ID: M2827 - Name: MTOR Inhibitors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M4311 - Name: Antitubercular Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016572 - Term: Cyclosporine - ID: D000009173 - Term: Mycophenolic Acid - ID: D000068338 - Term: Everolimus - ID: D000016559 - Term: Tacrolimus - ID: D000003524 - Term: Cyclosporins ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** CNI-regimen **Deaths Num At Risk:** 84 **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** EG000 **Other Num Affected:** 74 **Other Num at Risk:** 84 **Serious Number Affected:** 40 **Serious Number At Risk:** 84 **Title:** CNI-regimen **Group ID:** EG001 **Title:** CNI-free-regimen **Deaths Num Affected:** 1 **Deaths Num At Risk:** 78 **Description:** CNI-free regimen: MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and everolimus and corticosteroids; On month 6 to 9 only: Cyclosporin A or tacrolimus **ID:** EG001 **Other Num Affected:** 65 **Other Num at Risk:** 78 **Serious Number Affected:** 29 **Serious Number At Risk:** 78 **Title:** CNI-free-regimen **Frequency Threshold:** 5 #### Other Events **Term:** ANAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (20.0) **Term:** LEUKOPENIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (20.0) **Term:** SINUS TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) **Term:** TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HYPERTHYROIDISM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA (20.0) **Term:** APHTHOUS ULCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) **Term:** DIARRHOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) **Term:** NAUSEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) **Term:** VOMITING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) **Term:** FATIGUE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) **Term:** OEDEMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) **Term:** OEDEMA PERIPHERAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) **Term:** PYREXIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) **Term:** BRONCHITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) **Term:** CYTOMEGALOVIRUS INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) **Term:** NASOPHARYNGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) **Term:** ORAL HERPES **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) **Term:** RESPIRATORY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) **Term:** BLOOD CREATININE INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) **Term:** C-REACTIVE PROTEIN INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) **Term:** HYPERCHOLESTEROLAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HYPERLIPIDAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HYPERTRIGLYCERIDAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HYPERURICAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HYPOKALAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (20.0) **Term:** MUSCLE SPASMS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) **Term:** MYALGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) **Term:** OSTEOPOROSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) **Term:** PAIN IN EXTREMITY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HEADACHE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (20.0) **Term:** COUGH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (20.0) **Term:** DYSPNOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (20.0) **Term:** ACNE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (20.0) **Term:** RASH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (20.0) **Term:** HYPERTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (20.0) #### Serious Events **Term:** ANAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** ATRIAL FIBRILLATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 78 **Term:** ATRIAL FLUTTER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** CORONARY ARTERY STENOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** LEFT VENTRICULAR DYSFUNCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** PERICARDIAL EFFUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** SINUS TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** HYPERTHYROIDISM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** EYE PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** GLAUCOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** ABDOMINAL HERNIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** APHTHOUS ULCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** COLITIS ISCHAEMIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** DIARRHOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 78 **Term:** INGUINAL HERNIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** NAUSEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** VOMITING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** CHEST PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CHILLS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** FATIGUE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** OEDEMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** OEDEMA PERIPHERAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** PYREXIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 78 **Term:** STENOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CHOLECYSTITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CHOLECYSTITIS ACUTE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CHOLECYSTITIS CHRONIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CHOLELITHIASIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** HEART TRANSPLANT REJECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 78 **Term:** ANAL ABSCESS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** ASPERGILLOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** ASPERGILLUS INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** BACTERAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** BACTERIAL INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CAMPYLOBACTER GASTROENTERITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CLOSTRIDIUM DIFFICILE COLITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** CYTOMEGALOVIRUS INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** DEVICE RELATED INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** DIABETIC GANGRENE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** DIVERTICULITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** ENDOCARDITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** ESCHERICHIA INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** FEBRILE INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** GASTROENTERITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 78 **Term:** GASTROENTERITIS NOROVIRUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** GASTROENTERITIS SALMONELLA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** GROIN INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** H1N1 INFLUENZA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** HERPES SIMPLEX **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** HERPES ZOSTER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** HERPES ZOSTER INFECTION NEUROLOGICAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** INFECTED LYMPHOCELE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** INFECTIOUS PLEURAL EFFUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** INFLUENZA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** OTITIS EXTERNA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** PNEUMOCYSTIS JIROVECII PNEUMONIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** PNEUMONIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 78 **Term:** SEPTIC SHOCK **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** STAPHYLOCOCCAL INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** TUBERCULOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** UPPER RESPIRATORY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** URETERITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** URINARY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** WOUND INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** ACETABULUM FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** LUMBAR VERTEBRAL FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** VASCULAR PSEUDOANEURYSM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** BLOOD CREATININE INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** C-REACTIVE PROTEIN INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** HAEMOGLOBIN DECREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** INFLAMMATORY MARKER INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** WEIGHT INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** DEHYDRATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** BACK PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** OSTEOARTHRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** OSTEOPOROSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** B-CELL LYMPHOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** BLADDER CANCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** PLASMACYTOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** PROSTATE CANCER RECURRENT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** MYOCLONIC EPILEPSY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** SCIATICA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** SYNCOPE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** ACUTE KIDNEY INJURY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** CHRONIC KIDNEY DISEASE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** HAEMATURIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** RENAL ARTERY STENOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** RENAL FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** RENAL IMPAIRMENT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** URINARY RETENTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 78 **Term:** BENIGN PROSTATIC HYPERPLASIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** DYSPNOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** PULMONARY EMBOLISM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** PULMONARY MASS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** ANGIOEDEMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** DIABETIC FOOT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** SKIN HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** MEDICAL DEVICE REMOVAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** ANEURYSM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 84 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Term:** ANGIOPATHY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** DEEP VEIN THROMBOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Term:** HYPERTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (20.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 84 **Group ID:** EG001 **Num At Risk:** 78 **Time Frame:** Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 74 **Group ID:** BG001 **Value:** 71 **Group ID:** BG002 **Value:** 145 **Units:** Participants ### Group **ID:** BG000 **Title:** CNI-regimen **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids ### Group **ID:** BG001 **Title:** CNI-free-regimen **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.7 **Value:** 52.7 #### Measurement **Group ID:** BG001 **Spread:** 9.8 **Value:** 50.3 #### Measurement **Group ID:** BG002 **Spread:** 9.8 **Value:** 51.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 21 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 65 #### Measurement **Group ID:** BG001 **Value:** 59 #### Measurement **Group ID:** BG002 **Value:** 124 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 74 #### Measurement **Group ID:** BG001 **Value:** 71 #### Measurement **Group ID:** BG002 **Value:** 145 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Title:** Race (NIH/OMB) **Unit of Measure:** Participants **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** Novartis.email@novartis.com **Organization:** Novartis Pharmaceuticals **Phone:** 8627788300 **Title:** Study Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -16.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -6.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -11.3 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 6 to Month 9 **Non-Inferiority Comment:** difference **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** 0.203 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Fisher Exact **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 9 to Month 18 **Non-Inferiority Comment:** difference **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** 0.002 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Fisher Exact **Tested Non-Inferiority:** ### Outcome Measure 3 ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -19.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.3 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -14.0 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -16.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -6.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 18 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -11.3 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 5 ### Outcome Measure 6 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.008 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Wilcoxon (Mann-Whitney) **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.9 - **Upper Limit:** - **Value:** 54.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.0 - **Upper Limit:** - **Value:** 66.9 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 19.7 - **Upper Limit:** - **Value:** 54.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.4 - **Upper Limit:** - **Value:** 69.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 68 - **Group ID:** OG001 - **Value:** 62 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.9 - **Upper Limit:** - **Value:** 54.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.00 - **Upper Limit:** - **Value:** 66.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 69 - **Group ID:** OG001 - **Value:** 65 **Units:** Participants #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.49 - **Upper Limit:** - **Value:** 1.53 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.51 - **Upper Limit:** - **Value:** 1.49 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 71 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** 1.44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.35 - **Upper Limit:** - **Value:** 1.27 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 73 - **Group ID:** OG001 - **Value:** 70 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.75 - **Upper Limit:** - **Value:** 1.58 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.32 - **Upper Limit:** - **Value:** 1.24 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 70 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.53 - **Upper Limit:** - **Value:** 1.53 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.30 - **Upper Limit:** - **Value:** 1.20 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 70 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** 1.53 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.33 - **Upper Limit:** - **Value:** 1.22 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 70 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.50 - **Upper Limit:** - **Value:** 1.50 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.44 - **Upper Limit:** - **Value:** 1.27 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 71 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.364 - **Upper Limit:** - **Value:** 0.045 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.863 - **Upper Limit:** - **Value:** 0.403 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 cGFR (in mL/min/1.73 m2) = 186.3\*(C-1.154)\*(A-0.203)\*G\*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full Analysis Set-Last observation carried forward (FAS-LOCF)- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable but for this analysis only participants that had values at Month 18 were analyzed **Reporting Status:** POSTED **Time Frame:** Month 18 **Title:** Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 **Type:** PRIMARY **Unit of Measure:** mL/min ##### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** OG000 **Title:** CNI-regimen ##### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** OG001 **Title:** CNI-free-regimen #### Outcome Measure 2 **Description:** Treatment failure was defined as composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade ≥ 3A resp. ISHLT 2004 grade ≥ 2R, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present). If participant had an occurrence in each period it was counted for each period. **Parameter Type:** NUMBER **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Reporting Status:** POSTED **Time Frame:** Month 6 to Month 9; Month 9 to Month 18 **Title:** Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18 **Type:** SECONDARY **Unit of Measure:** Occurences ##### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** OG000 **Title:** CNI-regimen ##### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** OG001 **Title:** CNI-free-regimen #### Outcome Measure 3 **Description:** Major cardiac events (MACE) was defined as one of the following: any death, myocardial infarction, coronary artery bypass grafting **Parameter Type:** NUMBER **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Reporting Status:** POSTED **Time Frame:** Month 6 to Month 18 **Title:** Occurrence of Major Cardiac Events (MACE) From Month 6 to 18 **Type:** SECONDARY **Unit of Measure:** Occurences ##### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** OG000 **Title:** CNI-regimen ##### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** OG001 **Title:** CNI-free-regimen #### Outcome Measure 4 **Description:** Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 12 and 18. For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl) **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full Analysis Set-Last observation carried forward (FAS-LOCF)- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable but for this analysis only participants that had values at Month 12 \& 18 were analyzed **Reporting Status:** POSTED **Time Frame:** Month 12 and 18 **Title:** Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18 **Type:** SECONDARY **Unit of Measure:** mL/min ##### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** OG000 **Title:** CNI-regimen ##### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** OG001 **Title:** CNI-free-regimen #### Outcome Measure 5 **Description:** Serum Creatinine is an indicator of renal function measured in the blood **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Reporting Status:** POSTED **Time Frame:** Month 6, 8, 9, 10 12 and 18 **Title:** Serum Creatinine at Month 6, 8, 9, 10 12 and 18 **Type:** SECONDARY **Unit of Measure:** μmol/L ##### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** OG000 **Title:** CNI-regimen ##### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** OG001 **Title:** CNI-free-regimen #### Outcome Measure 6 **Description:** Reciprocal Creatinine Slope is an indication of renal function over time with a higher slope value indicating an improvement in renal function. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable **Reporting Status:** POSTED **Time Frame:** Between Month 6 and Month 18 **Title:** Reciprocal Creatinine Slope Between Month 6 and Month 18 **Type:** SECONDARY **Unit of Measure:** 1/(μmol/L)/(hour) ##### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** OG000 **Title:** CNI-regimen ##### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** OG001 **Title:** CNI-free-regimen ### Participant Flow Module #### Group **Description:** CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids **ID:** FG000 **Title:** CNI-regimen #### Group **Description:** CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids **ID:** FG001 **Title:** CNI-free-regimen #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Patient withdrew consent ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Administrative problems ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 84 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 78 ##### Milestone **Type:** Full Analysis Set (FAS) ###### Achievement **Group ID:** FG000 **Number of Subjects:** 74 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 71 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 76 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 71 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 7 **Recruitment Details:** 232 patients were screened, of these , 193 patients were included in safety set which included 31 non-randomized and 162 randomized. Of these, 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable and included in the Full Analysis Set FAS. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00452179 **Brief Title:** Safety and Efficacy Study of APD125 in Patient With Insomnia **Official Title:** A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Effects of APD125 in Patients With Chronic Primary Insomnia #### Organization Study ID Info **ID:** APD125-004 #### Organization **Class:** INDUSTRY **Full Name:** Arena Pharmaceuticals ### Status Module #### Completion Date **Date:** 2007-06 **Type:** ACTUAL #### Last Update Post Date **Date:** 2007-09-10 **Type:** ESTIMATED **Last Update Submit Date:** 2007-09-06 **Overall Status:** COMPLETED #### Start Date **Date:** 2007-02 **Status Verified Date:** 2007-09 #### Study First Post Date **Date:** 2007-03-27 **Type:** ESTIMATED **Study First Submit Date:** 2007-03-23 **Study First Submit QC Date:** 2007-03-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Arena Pharmaceuticals ### Description Module **Brief Summary:** The purpose of this study is to determine the effects of APD125 in patients with sleep maintenance insomnia. ### Conditions Module **Conditions:** - Insomnia **Keywords:** - Sleep maintenance - Insomnia - Sleep Consolidation - Sleep - Insomnia, primarily sleep maintenance ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 173 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** APD125 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Conventional PSG parameters #### Secondary Outcomes **Measure:** Patient reported subjective sleep parameters ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Primary insomnia as defined in DSM-IV-TR, with predominant complaint of impaired sleep maintenance and confirmed by PSG * PSQI \>/= to 5 * Qualifying screening PSG parameters * Generally good health Exclusion Criteria: * History of any sleep disorder, other than primary insomnia (e.g., restless leg syndrome, narcolepsy, sleep apnea, and disorders of REM/NREM sleep) * Any clinically significant medical condition, laboratory finding, or ECG finding * Pregnant and/or lactating females * History of substance abuse within 2 years or positive urine drug screen * Positive Hepatitis B/C results or HIV markers * Apnea-Hypopnea Index (AHI) or a Periodic Limb Movement Arousal Index (PLMAI) \> 10 as determined by screening PSG * History of treatment with an investigational drug within the last month * Recent travel involving crossing more than 3 time zones or plans to travel to another time zone (\> 3 time zones) during the study **Maximum Age:** 64 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Diego **Country:** United States **State:** California **Zip:** 92121 #### Overall Officials **Official 1:** **Affiliation:** Arena Pharmaceuticals **Name:** Warren A Prosser **Role:** STUDY_DIRECTOR ### References Module #### See Also Links **Label:** Arena Pharmaceuticals Home Page **URL:** http://www.arenapharm.com ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020919 - Term: Sleep Disorders, Intrinsic - ID: D000020920 - Term: Dyssomnias - ID: D000012893 - Term: Sleep Wake Disorders - ID: D000009422 - Term: Nervous System Diseases - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10356 - Name: Sleep Initiation and Maintenance Disorders - Relevance: HIGH - As Found: Insomnia - ID: M22242 - Name: Parasomnias - Relevance: LOW - As Found: Unknown - ID: M22654 - Name: Sleep Disorders, Intrinsic - Relevance: LOW - As Found: Unknown - ID: M22655 - Name: Dyssomnias - Relevance: LOW - As Found: Unknown - ID: M15696 - Name: Sleep Wake Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007319 - Term: Sleep Initiation and Maintenance Disorders ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04154579 **Brief Title:** Arts & Health Education to Improve Health, Resilience, and Well-Being **Official Title:** A Randomized Controlled Trial Utilizing the Arts to Improve Health, Resilience, and Well-Being in Individuals With Chronic Health Conditions in Underserved Neighborhoods #### Organization Study ID Info **ID:** IRB#19-854 #### Organization **Class:** OTHER **Full Name:** The Cleveland Clinic ### Status Module #### Completion Date **Date:** 2020-06-23 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-09-09 **Type:** ACTUAL **Last Update Submit Date:** 2022-09-06 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2020-06-23 **Type:** ACTUAL #### Start Date **Date:** 2019-07-01 **Type:** ACTUAL **Status Verified Date:** 2022-09 #### Study First Post Date **Date:** 2019-11-06 **Type:** ACTUAL **Study First Submit Date:** 2019-10-02 **Study First Submit QC Date:** 2019-11-04 **Why Stopped:** COVID-19 pandemic. Unable to restart as had hoped. ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** National Endowment for the Arts, United States **Class:** UNKNOWN **Name:** Cuyahoga Arts and Culture **Class:** OTHER **Name:** The Cleveland Clinic #### Lead Sponsor **Class:** OTHER **Name:** Lisa Gallagher #### Responsible Party **Investigator Affiliation:** The Cleveland Clinic **Investigator Full Name:** Lisa Gallagher **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an 8-week randomized controlled trial to help address health, resilience, and well-being. Participants are randomized into either a health education group or an arts-based health education group. Both groups will attend for 8 weeks and various study assessments will be conducted in order to measure the experience and impact of the program. Anyone 18 years and older with a chronic health condition (for example, diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disorder, asthma, weight, anxiety, depression, cardiac, arthritis, multiple sclerosis, and many more) are eligible to participate. **Detailed Description:** Within the healthcare field today there is an increased concern with public health, population health, wellness, and prevention, all of which include focusing on physical health, obesity, chronic health conditions, unhealthy lifestyles, aging, and mental health issues. As healthcare professionals attempt to improve individuals' health outcomes, quality of life, well-being, coping skills, and health indicators, they also must try to promote behavior change that helps keep patients out of the hospital. These are concerns faced by individuals of all ages, genders, ethnicities, cultural backgrounds, socioeconomic statuses, and diagnoses. Therefore, it is important to find multiple means of addressing these concerns with the various populations as it is likely that no one particular method would be effective for every individual. Programs and interventions have been created to address health, resilience, and well-being at the individual and the social level. They demonstrate the importance of providing support, encouraging behavior changes, and reinforcing objectives determined by the healthcare system. Many of these programs have focused on improving resilience and increasing participants' ability to thrive or recover from the illnesses and challenges they face. The broad problem to be addressed by this study is to assess if arts-based programs are superior to non-arts-based health education programs at improving individuals' physical and mental health outcomes, quality of life, well-being, resilience, coping skills, stress, and health indicators while promoting behavior change and keeping them out of the hospital. Previous programs have focused on improving resilience. Individual arts interventions such as music, art, craft, choir singing, writing, theater, and movement have been utilized and in many cases found to be helpful in addressing resilience, coping, health, and well-being; however, it is not known what effect a program utilizing multiple arts-based interventions would have on adults with chronic health conditions. The primary benefit of conducting research into the effectiveness of different arts-based programs is the identification of the specific benefits of programs aimed at influencing health, resilience, and well-being in individuals with a variety of chronic health conditions. The purpose of this randomized controlled study is to determine the outcomes of an 8-week arts-based program on the health, resilience, and well-being of individuals with chronic health conditions in an outpatient underserved community setting as compared to outcomes from individuals participating in a separate 8-week-non-arts-based health education program in the same setting. The purpose of including a variety of arts experiences is so that individuals will hopefully find at least one art form to which they can relate and will utilize in their lives to assist with their health, resilience, and well-being. The non-arts-based program will include educational topics related to health, resilience, and well-being. ### Conditions Module **Conditions:** - Hypertension - Diabetes - Obesity - COPD - CHF - High Cholesterol - Asthma - Chronic Pain - Multiple Sclerosis - Depression - Anxiety - Heart Diseases - Stroke **Keywords:** - Chronic health conditions - Arts-based program - Health education program - Health - Resilience - Well-being ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** This is a randomized controlled trial utilizing a mixed methods, pre-post intervention, and parallel group analysis. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This is an 8 week, arts-based session that includes educational \& experiential components. Topics include: Introduction to Arts \& Health; Music, Well-Being, \& Resilience; Movement \& Physical Activity; Art \& Well-Being; Writing \& Communication/Self-Expression; Theater \& Socialization; Art Appreciation \& a Healthy Brain; \& Summary/Integration of the Arts into Daily Lives. **Intervention Names:** - Behavioral: HeRe We Arts **Label:** HeRe We Arts **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This is an 8 week, non-arts-based health education session that includes educational \& some experiential components. Topics include: Introduction to Health, Resilience, \& Well-Being; Nutrition \& Healthy Eating; Exercise, Chair Yoga, \& Sleep; Mental Health, Stress Management, \& Life Satisfaction; Holistic Approaches: Wellness, Integrative Medicine, \& Complementary \& Alternative Medicine; Chronic Illnesses \& Chronic Pain; Health \& Behaviors; Summary \& Navigating the Healthcare System. **Intervention Names:** - Behavioral: HeRe We Ed **Label:** HeRe We Ed (Health Education Group) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - HeRe We Arts **Description:** Art Therapy interventions to promote health, resilience \& well-being will discussed; \& experiences such as key chain making, collaging on journal covers, creating sculpture garden will be utilized. Music therapy interventions such as lyric discussion, singing, instrument playing, \& music-assisted relaxation techniques will be utilized; \& discussion of use of music to elicit positive physical \& emotional responses will be held. Drums Alive (drumming \& movement) will be used to promote physical activity. Art appreciation will include discussion of public art forms. Journaling will include different techniques for journaling, writing poetry, etc. Theater games such as Password, Press Conference, Props Only, \& Draw What You Hear will be utilized. Chair yoga will be introduced as a form of exercise. Education will be provided on the various topics. **Name:** HeRe We Arts **Other Names:** - Music Therapy - Drums Alive - Art Appreciation - Journaling - Theater Games - Art Therapy **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - HeRe We Ed (Health Education Group) **Description:** Educational components and some experiential components will be utilized to educate the participants on health, resilience, well-being, nutrition, healthy eating, weight management, eating disorders, obesity, exercise, physical activity, sleep hygiene and the importance of sleep, mental health, stress management, the importance of improving life satisfaction, holistic approaches, wellness, integrative medicine, complementary and alternative medicine, chronic illness, chronic pain, methods for dealing with chronic versus acute illnesses, changing behaviors and/or maintaining healthy behaviors in order to promote health and stay out of the hospital, and navigating the healthcare system. Specific experiential components will include Chair Yoga and Stress Management Techniques. **Name:** HeRe We Ed **Other Names:** - Health Education - Chair Yoga - Stress Management Techniques **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Participants will identify a goal each week, and the next week they will report on whether or not they completed their goal. This does not include a scale. It is merely a Yes or No. **Measure:** Weekly Take-Away Goals **Time Frame:** Weeks 1-8 **Description:** Phenomenological interviews will be conducted in order to gather qualitative information regarding participants' experience with the program, as well as its impact and meaning in their lives. This does not include a scale. It involves open-ended, qualitative information that is shared. **Measure:** Phone Interview **Time Frame:** Week 9 **Description:** Survey to determine progress, maintenance, and/or follow through at Week 16 (2 months after completion of the program). This does not involve a scale. It seeks to determine if skills are still being used 16 weeks after the start of the program via the use of open-ended and multiple choice questions. **Measure:** HeRe We Arts Week 16 Survey **Time Frame:** Week 16 **Description:** Survey to determine progress, maintenance, and/or follow through at Week 16 (2 months after completion of the program). This does not involve a scale. It seeks to determine if skills are still being used 16 weeks after the start of the program via the use of open-ended and multiple choice questions. **Measure:** HeRe We Ed Week 16 Survey **Time Frame:** Week 16 #### Primary Outcomes **Description:** Means of assessing change in mood. Contains 6 items, 3 negative \& 3 positive. Participants think about how they felt in the past 7 days \& rate the frequency of each item on a 4-point scale. Scale ranges include scores between 0 and 18. Higher scores indicate higher levels of happiness. **Measure:** Change in Short Depression-Happiness Scale from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** Means of assessing change in mood. Contains 6 items, 3 negative \& 3 positive. Participants think about how they felt in the past 7 days \& rate the frequency of each item on a 4-point scale. Scale ranges include scores between 0 and 18. Higher scores indicate higher levels of happiness. **Measure:** Change in Short Depression-Happiness Scale from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** Means of assessing change in mood. Contains 6 items, 3 negative \& 3 positive. Participants think about how they felt in the past 7 days \& rate the frequency of each item on a 4-point scale. Scale ranges include scores between 0 and 18. Higher scores indicate higher levels of happiness. **Measure:** Change in Short Depression-Happiness Scale from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** Participants answer 7 questions by choosing the answer that best describes their experience over the last 2 weeks. Designed to measure the feeling and functioning aspects of positive mental well-being. Scores range from 7 to 35. Higher scores represent higher positive mental well-being. **Measure:** Change in Short Warwick-Edinburgh Mental Well-Being Scale from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** Participants answer 7 questions by choosing the answer that best describes their experience over the last 2 weeks. Designed to measure the feeling and functioning aspects of positive mental well-being. Scores range from 7 to 35. Higher scores represent higher positive mental well-being. **Measure:** Change in Short Warwick-Edinburgh Mental Well-Being Scale from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** Participants answer 7 questions by choosing the answer that best describes their experience over the last 2 weeks. Designed to measure the feeling and functioning aspects of positive mental well-being. Scores range from 7 to 35. Higher scores represent higher positive mental well-being. **Measure:** Change in Short Warwick-Edinburgh Mental Well-Being Scale from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** A 4-item measure designed to identify participants' abilities to cope with stress. It may be helpful for recognizing those who may need to learn techniques to help improve their coping skills and resilience. Scores range from 4-20. Scores of 4-13 represent low resilient copers, those of 14-16 represent medium resilient copers, and those of 17-20 represent high resilient copers. **Measure:** Change in Brief Resilient Coping Scale from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** A 4-item measure designed to identify participants' abilities to cope with stress. It may be helpful for recognizing those who may need to learn techniques to help improve their coping skills \& resilience. Scores range from 4-20. Scores of 4-13 represent low resilient copers, those of 14-16 represent medium resilient copers, and those of 17-20 represent high resilient copers. **Measure:** Change in Brief Resilient Coping Scale from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** A 4-item measure designed to identify participants' abilities to cope with stress. It may be helpful for recognizing those who may need to learn techniques to help improve their coping skills \& resilience. Scores range from 4-20. Scores of 4-13 represent low resilient copers, those of 14-16 represent medium resilient copers, and those of 17-20 represent high resilient copers. **Measure:** Change in Brief Resilient Coping Scale from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** Measures amount of physical activity. Asks participants how many times on average, over a 7-day period, they engage in strenuous, moderate, or mild exercise for more than 15 minutes, and the average frequency of activity that leads to increased heart rate. Scores range from 0-24. Higher scores indicate higher levels of physical activity. **Measure:** Change in Godin-Shephard Leisure-Time Physical Activity Questionnaire from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** Measures amount of physical activity. Asks participants how many times on average, over a 7-day period, they engage in strenuous, moderate, or mild exercise for more than 15 minutes, and the average frequency of activity that leads to increased heart rate. Scores range from 0-24. Higher scores indicate higher levels of physical activity. **Measure:** Change in Godin-Shephard Leisure-Time Physical Activity Questionnaire from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** Measures amount of physical activity. Asks participants how many times on average, over a 7-day period, they engage in strenuous, moderate, or mild exercise for more than 15 minutes, and the average frequency of activity that leads to increased heart rate. Scores range from 0-24. Higher scores indicate higher levels of physical activity. **Measure:** Change in Godin-Shephard Leisure-Time Physical Activity Questionnaire from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** A self-report measure to identify symptoms, feelings, behaviors, \& functions in the areas of physical, mental, \& social health. Raw scores for mental health and for physical health are translated into T-scores. The mean for the T-score is 50 and there is a standard deviation of 10. Therefore, a higher T-score represents higher physical health or higher mental health. **Measure:** Change in PROMIS Scale v1.2 - Global Health from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** A self-report measure to identify symptoms, feelings, behaviors, \& functions in the areas of physical, mental, \& social health. Raw scores for mental health and for physical health are translated into T-scores. The mean for the T-score is 50 and there is a standard deviation of 10. Therefore, a higher T-score represents higher physical health or higher mental health. **Measure:** Change in PROMIS Scale v1.2 - Global Health from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** A self-report measure to identify symptoms, feelings, behaviors, \& functions in the areas of physical, mental, \& social health. Raw scores for mental health and for physical health are translated into T-scores. The mean for the T-score is 50 and there is a standard deviation of 10. Therefore, a higher T-score represents higher physical health or higher mental health. **Measure:** Change in PROMIS Scale v1.2 - Global Health from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** At the start of each session an investigator will take and document each participants' systolic and diastolic blood pressure. **Measure:** Change in Systolic and Diastolic Blood Pressure from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** At the start of each session an investigator will take and document each participants' systolic and diastolic blood pressure. **Measure:** Change in Systolic and Diastolic Blood Pressure from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** At the start of each session an investigator will take and document each participants' systolic and diastolic blood pressure. **Measure:** Change in Systolic and Diastolic Blood Pressure from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** At the start of each session an investigator will take and document each participant's heart rate. **Measure:** Change in Heart Rate from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** At the start of each session an investigator will take and document each participant's heart rate. **Measure:** Change in Heart Rate from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** At the start of each session an investigator will take and document each participant's heart rate. **Measure:** Change in Heart Rate from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 **Description:** At the start of each session an investigator will take and document each participant's pulse oximetry. **Measure:** Change in Pulse Oximetry from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** At the start of each session an investigator will take and document each participant's pulse oximetry. **Measure:** Change in Pulse Oximetry from Week 8 to Week 16 **Time Frame:** Weeks 8 and 16 **Description:** At the start of each session an investigator will take and document each participant's pulse oximetry. **Measure:** Change in Pulse Oximetry from Week 1 to Week 16 **Time Frame:** Weeks 1 and 16 #### Secondary Outcomes **Description:** A pre-test/post-survey utilized to test knowledge on arts and well-being, as well as satisfaction at endpoints. This is not a standardized measure and does not include a scale. It involves changes in knowledge and use of arts techniques, as well as satisfaction with the program via the use of open-ended and multiple choice questions. **Measure:** Change in HeRe We Arts Survey from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** A pre-test/post-test utilized to test knowledge on health education \& well-being, as well as satisfaction, at endpoints. This is not a standardized measure and does not include a scale. It involves changes in knowledge and use of arts techniques, as well as satisfaction with the program via the use of open-ended and multiple choice questions. **Measure:** Change in HeRe We Ed Survey from Week 1 to Week 8 **Time Frame:** Weeks 1 and 8 **Description:** Completed by participants at the end of each session in order to obtain information on learning and satisfaction. This is not a standardized measure and does not include a scale. It involves changes in knowledge and use of arts techniques, as well as satisfaction with the program via the use of open-ended and multiple choice questions. **Measure:** Weekly Post-Session Survey **Time Frame:** Weeks 1-8 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * At least 18 years old * Diagnosed with at least one chronic health condition (as reported by the participant) * Able to participate safely in all program sessions * Proficient in English * Cognitively able to consent to participate Exclusion Criteria: * Severe visual or auditory impairment * Severe and/or uncontrolled comorbidity precluding safe participation in the program **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Euclid **Country:** United States **Facility:** Cleveland Clinic Euclid Hospital **State:** Ohio **Zip:** 44119 #### Overall Officials **Official 1:** **Affiliation:** The Cleveland Clinic **Name:** Lisa M Gallagher, MA **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Ahern NR, Kiehl EM, Sole ML, Byers J. A review of instruments measuring resilience. Issues Compr Pediatr Nurs. 2006 Apr-Jun;29(2):103-25. doi: 10.1080/01460860600677643. **PMID:** 16772239 **Citation:** Beesley K, White JH, Alston MK, Sweetapple AL, Pollack M. Art after stroke: the qualitative experience of community dwelling stroke survivors in a group art programme. Disabil Rehabil. 2011;33(23-24):2346-55. doi: 10.3109/09638288.2011.571333. Epub 2011 Apr 18. **PMID:** 21501042 **Citation:** Connor KM, Davidson JR. Development of a new resilience scale: the Connor-Davidson Resilience Scale (CD-RISC). Depress Anxiety. 2003;18(2):76-82. doi: 10.1002/da.10113. **PMID:** 12964174 **Citation:** Davydov DM, Stewart R, Ritchie K, Chaudieu I. Resilience and mental health. Clin Psychol Rev. 2010 Jul;30(5):479-95. doi: 10.1016/j.cpr.2010.03.003. Epub 2010 Mar 25. **PMID:** 20395025 **Citation:** Deshields TL, Heiland MF, Kracen AC, Dua P. Resilience in adults with cancer: development of a conceptual model. Psychooncology. 2016 Jan;25(1):11-8. doi: 10.1002/pon.3800. Epub 2015 Mar 18. **PMID:** 25787828 **Citation:** Dingle GA, Williams E, Jetten J, Welch J. Choir singing and creative writing enhance emotion regulation in adults with chronic mental health conditions. Br J Clin Psychol. 2017 Nov;56(4):443-457. doi: 10.1111/bjc.12149. Epub 2017 Jul 18. **PMID:** 28722166 **Citation:** Fancourt D, Perkins R, Ascenso S, Carvalho LA, Steptoe A, Williamon A. Effects of Group Drumming Interventions on Anxiety, Depression, Social Resilience and Inflammatory Immune Response among Mental Health Service Users. PLoS One. 2016 Mar 14;11(3):e0151136. doi: 10.1371/journal.pone.0151136. eCollection 2016. **PMID:** 26974430 **Citation:** Gallagher LM, Lagman R, Bates D, Edsall M, Eden P, Janaitis J, Rybicki L. Perceptions of family members of palliative medicine and hospice patients who experienced music therapy. Support Care Cancer. 2017 Jun;25(6):1769-1778. doi: 10.1007/s00520-017-3578-y. Epub 2017 Jan 19. **PMID:** 28105524 **Citation:** Gallagher LM, Lagman R, Rybicki L. Outcomes of Music Therapy Interventions on Symptom Management in Palliative Medicine Patients. Am J Hosp Palliat Care. 2018 Feb;35(2):250-257. doi: 10.1177/1049909117696723. Epub 2017 Mar 9. **PMID:** 28274132 **Citation:** Gloria CT, Steinhardt MA. Relationships Among Positive Emotions, Coping, Resilience and Mental Health. Stress Health. 2016 Apr;32(2):145-56. doi: 10.1002/smi.2589. Epub 2014 Jun 24. **PMID:** 24962138 **Citation:** Goubert L, Trompetter H. Towards a science and practice of resilience in the face of pain. Eur J Pain. 2017 Sep;21(8):1301-1315. doi: 10.1002/ejp.1062. Epub 2017 Jun 2. **PMID:** 28573783 **Citation:** Khan WU, Moss H. Increasing Public Health Awareness of and Capacity for Arts-Based Therapy in Medicine. JAMA Neurol. 2017 Sep 1;74(9):1029-1030. doi: 10.1001/jamaneurol.2017.1639. No abstract available. **PMID:** 28783804 **Citation:** Lesiuk T. The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study. Oncol Nurs Forum. 2015 May;42(3):276-82. doi: 10.1188/15.ONF.276-282. **PMID:** 25901379 **Citation:** Orjasaeter KB, Ness O. Acting Out: Enabling Meaningful Participation Among People With Long-Term Mental Health Problems in a Music and Theater Workshop. Qual Health Res. 2017 Sep;27(11):1600-1613. doi: 10.1177/1049732316679954. Epub 2016 Nov 28. **PMID:** 27899473 **Citation:** Petriwskyj A, Parker D, O'Dwyer S, Moyle W, Nucifora N. Interventions to build resilience in family caregivers of people living with dementia: a comprehensive systematic review. JBI Database System Rev Implement Rep. 2016 Jun;14(6):238-73. doi: 10.11124/JBISRIR-2016-002555. **PMID:** 27532659 **Citation:** Phinney A, Moody EM, Small JA. The Effect of a Community-Engaged Arts Program on Older Adults' Well-being. Can J Aging. 2014 Sep;33(3):336-45. doi: 10.1017/S071498081400018X. Epub 2014 Aug 11. **PMID:** 25110936 **Citation:** Robb SL, Burns DS, Stegenga KA, Haut PR, Monahan PO, Meza J, Stump TE, Cherven BO, Docherty SL, Hendricks-Ferguson VL, Kintner EK, Haight AE, Wall DA, Haase JE. Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group. Cancer. 2014 Mar 15;120(6):909-17. doi: 10.1002/cncr.28355. Epub 2014 Jan 27. **PMID:** 24469862 **Citation:** Stuckey HL, Nobel J. The connection between art, healing, and public health: a review of current literature. Am J Public Health. 2010 Feb;100(2):254-63. doi: 10.2105/AJPH.2008.156497. Epub 2009 Dec 17. **PMID:** 20019311 **Citation:** Swarthout M, Bishop MA. Population health management: Review of concepts and definitions. Am J Health Syst Pharm. 2017 Sep 15;74(18):1405-1411. doi: 10.2146/ajhp170025. **PMID:** 28887342 **Citation:** Zarobe L, Bungay H. The role of arts activities in developing resilience and mental wellbeing in children and young people a rapid review of the literature. Perspect Public Health. 2017 Nov;137(6):337-347. doi: 10.1177/1757913917712283. Epub 2017 Jun 14. **PMID:** 28613107 **Citation:** Ali A, Wolfert S. Theatre as a treatment for posttraumatic stress in military veterans: Exploring the psychotherapeutic potential of mimetic induction. The Arts in Psychotherapy 50: 58-65, 2016. **Citation:** Bennington R, Backso A, Harrison J, Reader AE, Carolan R. Art therapy in art museums: Promoting social connectedness and psychological well-being of older adults. The Arts in Psychotherapy 49: 34-43, 2016. **Citation:** Coholic D, Eys, M, Lougheed S. Investigating the effectiveness of an arts-based and mindfulness-based group program for the improvement of resilience in children in need. 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Crafting, health, and wellbeing: Findings from the survey of public participation in the arts and considerations for art therapists. Arts & Health 9(1): 81-90, 2017. **Citation:** Kindig D, Stoddart G. What is population health? Am J Public Health. 2003 Mar;93(3):380-3. doi: 10.2105/ajph.93.3.380. **PMID:** 12604476 **Citation:** Letwin L, Silverman MJ. No between-group difference but tendencies for patient support: A pilot study of a resilience-focused music therapy protocol for adults on a medical oncology/hematology unit. The Arts in Psychotherapy 55: 116-125, 2017. **Citation:** Pasiali V. Resilience, music therapy, and human adaptation: Nurturing young children and families. Nordic Journal of Music Therapy 21(1): 36-56, 2012. **Citation:** Rankanen M. Clients' experiences of the impacts of an experiential art therapy group. The Arts in Psychotherapy 50: 101-110, 2016. **Citation:** Sabogal M. 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Arizona State University, Tempe, AZ, 2016. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000006949 - Term: Hyperlipidemias - ID: D000050171 - Term: Dyslipidemias - ID: D000052439 - Term: Lipid Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: LOW - As Found: Unknown - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M7058 - Name: Depression - Relevance: LOW - As Found: Unknown - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M7061 - Name: Depressive Disorder - Relevance: LOW - As Found: Unknown - ID: M4556 - Name: Asthma - Relevance: LOW - As Found: Unknown - ID: M22306 - Name: Stroke - Relevance: LOW - As Found: Unknown - ID: M29442 - Name: Chronic Pain - Relevance: HIGH - As Found: Chronic Pain - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: HIGH - As Found: Heart Disease - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M9988 - Name: Hypercholesterolemia - Relevance: HIGH - As Found: High Cholesterol - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M10000 - Name: Hyperlipidemias - Relevance: LOW - As Found: Unknown - ID: M10002 - Name: Hyperlipoproteinemias - Relevance: LOW - As Found: Unknown - ID: M26181 - Name: Dyslipidemias - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000006331 - Term: Heart Diseases - ID: D000006937 - Term: Hypercholesterolemia - ID: D000059350 - Term: Chronic Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05923879 **Brief Title:** Mechanism Investigation of Selinexor Combined With Lenalidomide and Rituximab in the Treatment of Diffuse Large B-cell Lymphoma **Official Title:** Mechanism Investigation of Selinexor Combined With Lenalidomide and Rituximab in the Treatment of Diffuse Large B-cell Lymphoma #### Organization Study ID Info **ID:** SR2-DLBCL #### Organization **Class:** OTHER **Full Name:** Ruijin Hospital ### Status Module #### Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2023-06-30 **Type:** ESTIMATED **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2023-06-28 **Type:** ACTUAL **Study First Submit Date:** 2023-06-03 **Study First Submit QC Date:** 2023-06-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ruijin Hospital #### Responsible Party **Investigator Affiliation:** Ruijin Hospital **Investigator Full Name:** Zhao Weili **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** This is a retrospective observational study of the therapeutic mechanism and resistance mechanism of the treatment of Selinexor combined with lenalidomide and rituximab in diffuse large B-cell lymphoma patients. By detecting the immune cells in peripheral blood and tumor tissues of patients before and after treatment, the key immune cell subsets and immune molecules linked to the action and resistance of the treatment of Selinexor combined with lenalidomide and rituximab, so as to provide the basis for the optimization of the treatment or the combination of other immunotherapies. ### Conditions Module **Conditions:** - Lymphoma, Large B-Cell, Diffuse ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Selinexor combined with lenalidomide and rituximab **Name:** Selinexor combined with lenalidomide and rituximab **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Tumor tissues collected before treatment and at the point of progression if available for DNA sequencing after quality control. On the one hand, the difference of tumor mutations will be analyzed in pre-treatment biopsy samples of patients grouped by efficacy; on the other hand, the changes of tumor mutations will be analyzed between pre-treatment and post-treatment biopsy samples of patients. **Measure:** Tumor tissues collected before treatment and at the point of progression if available for DNA sequencing after quality control. **Time Frame:** 2023/06/30-2025/06/30 **Description:** Tumor tissues collected before treatment and at the point of progression if available for bulky RNA sequencing, single-cell RNA sequencing and spatial transcriptome sequencing after quality control. On the one hand, the difference of characteristics of tumor microenvironment will be analyzed in pre-treatment biopsy samples of patients grouped by efficacy; on the other hand, the changes of characteristics of tumor microenvironment will be analyzed between pre-treatment and post-treatment biopsy samples of patients. **Measure:** Tumor tissues collected before treatment and at the point of progression if available for RNA sequencing after quality control. **Time Frame:** 2023/06/30-2025/06/30 **Description:** Peripheral blood collected before each cycle and at the point of progression if available for Mass Cytometry to analyze the changes of immune celltypes and chemokines and cytokines. **Measure:** Peripheral blood collected before each cycle and at the point of progression if available for Mass Cytometry. **Time Frame:** 2023/06/30-2025/06/30 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. At least 18 years old. 2. Histopathologically confirmed diffuse large B-cell lymphoma according to World Health Organization (WHO) classification criteria 2016. 3. There is evidence of relapsed or refractory disease. 4. Treatment with Selinexor combined with lenalidomide and rituximab. Exclusion Criteria: * No **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Over 18-year-old recurrent or refractory diffuse large B-cell lymphoma patients receiving Selinexor combined with lenalidomide and rituximab would be enrolled. ### Contacts Locations Module #### Locations **Location 1:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Email:** zwl_trial@163.com - **Name:** Weili Zhao - **Role:** CONTACT **Country:** China **Facility:** Ruijin Hospital, Shanghai Jiao Tong University School of Medicine ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000016393 - Term: Lymphoma, B-Cell - ID: D000008228 - Term: Lymphoma, Non-Hodgkin ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: HIGH - As Found: Lymphoma - ID: M18831 - Name: Lymphoma, Large B-Cell, Diffuse - Relevance: HIGH - As Found: Lymphoma, Large B-Cell, Diffuse - ID: M18828 - Name: Lymphoma, B-Cell - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M11222 - Name: Lymphoma, Non-Hodgkin - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma - ID: T640 - Name: B-cell Lymphoma - Relevance: HIGH - As Found: B-cell Lymphoma - ID: T1866 - Name: Diffuse Large B-Cell Lymphoma - Relevance: HIGH - As Found: Diffuse Large B-Cell Lymphoma ### Condition Browse Module - Meshes - ID: D000008223 - Term: Lymphoma - ID: D000016403 - Term: Lymphoma, Large B-Cell, Diffuse ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018501 - Term: Antirheumatic Agents - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000006131 - Term: Growth Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M373 - Name: Rituximab - Relevance: HIGH - As Found: Healthy - ID: M1725 - Name: Lenalidomide - Relevance: HIGH - As Found: Respiratory - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069283 - Term: Rituximab - ID: D000077269 - Term: Lenalidomide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00836979 **Acronym:** RRISK3 **Brief Title:** Urinary Incontinence: Reproductive/Hormonal Risk Factors **Official Title:** Urinary Incontinence: Reproductive/Hormonal Risk Factors III #### Organization Study ID Info **ID:** CN-08Svand-01-H #### Organization **Class:** OTHER **Full Name:** Kaiser Permanente #### Secondary ID Infos **ID:** P50DK064538 **Link:** https://reporter.nih.gov/quickSearch/P50DK064538 **Type:** NIH ### Status Module #### Completion Date **Date:** 2012-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-04-07 **Type:** ESTIMATED **Last Update Submit Date:** 2015-04-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Start Date **Date:** 2008-10 **Status Verified Date:** 2015-04 #### Study First Post Date **Date:** 2009-02-04 **Type:** ESTIMATED **Study First Submit Date:** 2009-02-03 **Study First Submit QC Date:** 2009-02-03 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of California, San Francisco #### Lead Sponsor **Class:** OTHER **Name:** Kaiser Permanente #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is a continuation or follow-up of two previous studies (RRISK and RRISK2) conducted at the Kaiser Division of Research. This study will invite previous study participants, as well as a randomly selected group of Northern California Kaiser Permanente Members, to participate in an interview, mailed survey and lab visit. The purpose of this study is to examine the risk factors for bladder and pelvic problems. **Detailed Description:** Using a cohort established during two previous studies (RRISK, CN-97Svand-01-H and RRISK2 CN-02Svand-07-H), this study will follow a well characterized cohort of middle-aged and older women who have been members of Kaiser Permanente Medical Care Plan (KPMCP) of Northern California continuously since age 18. The cohort is composed of over 2000 women for whom we have data from abstracted medical records, in-person interview, voiding diaries, physical assessments, laboratory data, and banked sera. Our cohort is unique in including a substantial number of women from the 4 major ethnic/race groups (white non-Hispanic, Black, Asian and Hispanic.) For this study, we will re-interview as many study participants from RRISK and RRISK2 as are willing. This study will also expand to further increase its diversity by adding a total of 450 Black, Asian and Hispanic women to the cohort. The overall goal of the study is to advance our understanding of mechanisms of Urinary Incontinence and facilitate the translational development of novel approaches to treatment and prevention. ### Conditions Module **Conditions:** - Urinary Incontinence **Keywords:** - Urinary Incontinence - Incontinence - bladder problems - bladder dysfunction ### Design Module #### Bio Spec **Description:** Sera will be banked for this cohort. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 2161 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Other Outcomes **Description:** To further characterize the association between hormones and UI and to determine if phytoestrogens are a risk factor for UI we will (a) use pharmacy records, supplemented by self-report, to ascertain the type, dose, duration and delivery for estrogens and for selective estrogen reuptake inhibitors (SERMs) and test their association with UI; (b) estimate phytoestrogen exposure from self-reported intake of key foods and botanicals and test the association with UI using multivariate analysis. **Measure:** Hormones **Time Frame:** up to 48 months **Description:** To test the association between estrogen receptor gene polymorphisms and UI we will use banked serum samples from the RRISK cohort to assay for polymorphisms of the two estrogen receptor genes (ESR1 and ESR2) and determine their associations with urinary incontinence. **Measure:** Gene Polymorphisms **Time Frame:** up to 48 months **Description:** We will analyze approximately 20,000 person-years of observational data using multiple regression techniques to (a) determine rates of new UI and changes in UI frequency/severity (including remission) and (b) identify risk factors for new UI and change in UI severity. **Measure:** New UI and Progressive UI **Time Frame:** up to 48 months **Description:** To investigate the association between pre-diabetes and increased risk of UI recently reported by members of our group we will (a) examine the cross-sectional association between pre-diabetes and UI, controlling for multiple other variables including body mass, waist circumference, inflammatory markers, and coronary heart disease; (b) conduct in-person interviews, measure physical parameters, and obtain blood tests on the approximately 400 women in the current study cohort with pre-diabetes. This additional prospective data on pre-diabetic women will allow us to characterize the natural history of the association between pre-diabetes and progression or new onset of UI. **Measure:** Pre-Diabetes **Time Frame:** up to 48 months #### Primary Outcomes **Description:** To investigate the two- to three-fold greater prevalence of stress UI in White women, compared to Black and Asian women which we previously reported we will (a) create and compare risk factor models of UI for each racial/ethnic group (White, Black, Hispanic, Asian); b) determine the extent to which racial differences can be explained by differences in newly measured exposures and genetic polymorphisms in addition to previously identified risk factors. To increase study power, we will enroll an additional 450 women (150 Black, 150 Asian and 150 Hispanic) into the RRRISK cohort. **Measure:** Race/Ethnicity **Time Frame:** up to 48 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * previously participated in the RRISK or RRISK2 studies at the kaiser Division of Research. Exclusion Criteria: * Not a part of the previous RRISK or RRISK2 cohorts. **Maximum Age:** 69 Years **Minimum Age:** 40 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** A previously identified cohort of approximately 2000 women who are members of Kaiser Permanente Northern California (KPNC) health plan, having seen a Provider for bladder/incontinence related issues and have previously participated in the RRISK and RRISK2 studies. We will also randomly identify an additional cohort of women who are current members KPNC which report race/ethnicity as Asian, Hispanic or Black/African American (to total an additional 450 women across all groups.) ### Contacts Locations Module #### Locations **Location 1:** **City:** Oakland **Country:** United States **Facility:** Kaiser Division of Research **State:** California **Zip:** 94612 #### Overall Officials **Official 1:** **Affiliation:** Kaiser Division of Research **Name:** Stephen K Van Den Eeden, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** UCSF/Mr. Zion WHCRC **Name:** Jeanette Brown, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** UCSF/Family and Community Medicine **Name:** David Thom, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014555 - Term: Urination Disorders - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000059411 - Term: Lower Urinary Tract Symptoms - ID: D000020924 - Term: Urological Manifestations - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019960 - Term: Elimination Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M17299 - Name: Urinary Incontinence - Relevance: HIGH - As Found: Urinary Incontinence - ID: M7936 - Name: Enuresis - Relevance: HIGH - As Found: Urinary Incontinence - ID: M27171 - Name: Nocturnal Enuresis - Relevance: LOW - As Found: Unknown - ID: M17305 - Name: Urination Disorders - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M29464 - Name: Lower Urinary Tract Symptoms - Relevance: LOW - As Found: Unknown - ID: M22659 - Name: Urological Manifestations - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21832 - Name: Elimination Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014549 - Term: Urinary Incontinence - ID: D000004775 - Term: Enuresis ### Intervention Browse Module - Browse Branches - Abbrev: Coag - Name: Coagulants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16684 - Name: Thromboplastin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00001679 **Brief Title:** Prognostic Indicators and Determinants of the 2-5 Year Outcome in a Cohort of Early Synovitis Patients **Official Title:** Prognostic Indicators and Determinants of the 2-5 Year Outcome in a Cohort of Early Synovitis Patients #### Organization Study ID Info **ID:** 980150 #### Organization **Class:** NIH **Full Name:** National Institutes of Health Clinical Center (CC) #### Secondary ID Infos **ID:** 98-AR-0150 ### Status Module #### Completion Date **Date:** 2000-06 #### Expanded Access Info #### Last Update Post Date **Date:** 2008-03-04 **Type:** ESTIMATED **Last Update Submit Date:** 2008-03-03 **Overall Status:** COMPLETED #### Start Date **Date:** 1998-08 **Status Verified Date:** 1999-08 #### Study First Post Date **Date:** 2002-12-10 **Type:** ESTIMATED **Study First Submit Date:** 1999-11-03 **Study First Submit QC Date:** 2002-12-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ### Description Module **Brief Summary:** This study will evaluate the 2-5 year outcome of a cohort of 250 patients with early synovitis, who were recruited into protocol 94-AR-0194 (The Pathogenesis of Inflammatory Synovitis: A Study of Early Arthritis). Clinical, radiographic, and functional outcome parameters, particularly those relating to articular damage and functional loss, will be evaluated and related back to clinical, serologic, immunogenetic, and pathologic variables identified at the onset of the arthropathy. A model will be generated which incorporates and weighs the variables in order to determine diagnostic and prognostic markers in the early stages of arthritis. Synovial tissue samples have been obtained from the entire cohort at the initial visit of protocol 94-AR-0194. Studies of these biopsies have so far demonstrated evidence for the presence of infectious agents in a proportion of the samples, and have generated information regarding the cytokine profiles in the early stages of synovitis. In an attempt to further define the pathogenetic mechanisms of synovitis longitudinally, biopsies will be repeated on selected subsets of the cohort. Specific questions to be answered relate to the persistence of microbial agents in the synovium, and to the evolution of cellular and molecular mechanisms which mediate the invasive, destructive potential of the synovial lesion. It is anticipated that these studies should prove valuable to clinicians who are attempting to stratify patients for therapeutic strategies, early in their disease course. They should also prove valuable in enhancing the understanding of the pathogenetic mechanisms of synovitis. **Detailed Description:** This study will evaluate the 2-5 year outcome of a cohort of 250 patients with early synovitis, who were recruited into protocol 94-AR-0194 (The Pathogenesis of Inflammatory Synovitis: A Study of Early Arthritis). Clinical, radiographic, and functional outcome parameters, particularly those relating to articular damage and functional loss, will be evaluated and related back to clinical, serologic, immunogenetic, and pathologic variables identified at the onset of the arthropathy. A model will be generated which incorporates and weighs the variables in order to determine diagnostic and prognostic markers in the early stages of arthritis. Synovial tissue samples have been obtained from the entire cohort at the initial visit of protocol 94-AR-0194. Studies of these biopsies have so far demonstrated evidence for the presence of infectious agents in a proportion of the samples, and have generated information regarding the cytokine profiles in the early stages of synovitis. In an attempt to further define the pathogenetic mechanisms of synovitis longitudinally, biopsies will be repeated on selected subsets of the cohort. Specific questions to be answered relate to the persistence of microbial agents in the synovium, and to the evolution of cellular and molecular mechanisms which mediate the invasive, destructive potential of the synovial lesion. It is anticipated that these studies should prove valuable to clinicians who are attempting to stratify patients for therapeutic strategies, early in their disease course. They should also prove valuable in enhancing the understanding of the pathogenetic mechanisms of synovitis. ### Conditions Module **Conditions:** - Arthritis, Reactive - Arthritis, Rheumatoid - Synovitis **Keywords:** - Immunogenetics - Joint Damage - Reactive Arthritis - Rheumatoid Arthritis - Synovium - Synovitis ### Design Module #### Enrollment Info **Count:** 250 **Study Type:** OBSERVATIONAL ### Eligibility Module **Eligibility Criteria:** All patients who have been recruited into, and completed, the 1 year follow up of protocol 94-AR-0194. FOR ENTRY ONTO 98-AR-0150 JOINT MRI: Patients currently being evaluated at the NIH through Protocol 94-AR-0194 or 98-AR-1050. Must have at least one clinically active arthritic joint that is under consideration for percutaneous needle synovial biopsy. No patients who have any of the following: cardiac pacemakers, auto defribrillators, neural stimulators, aneurysm clips, metallic prostheses, cochlear (ear) implants, any implanted devices (pumps, infusion devices, etc.), metal fragments in the eye, or shrapnel injuries. No patients who exceed the size limitations of the MRI scanner. No patients who suffer from claustrophobia. No patients who have had a previous anaphylactoid reaction to gadolinium-based contrast material. No patients who are currently pregnant. **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bethesda **Country:** United States **Facility:** National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) **State:** Maryland **Zip:** 20892 ### References Module #### References **Citation:** Emery P, Symmons DP. What is early rheumatoid arthritis?: definition and diagnosis. Baillieres Clin Rheumatol. 1997 Feb;11(1):13-26. doi: 10.1016/s0950-3579(97)80030-1. **PMID:** 9088522 **Citation:** Harrison BJ, Symmons DP, Brennan P, Bankhead CR, Barrett EM, Scott DG, Silman AJ. Inflammatory polyarthritis in the community is not a benign disease: predicting functional disability one year after presentation. J Rheumatol. 1996 Aug;23(8):1326-31. **PMID:** 8856609 **Citation:** Hulsemann JL, Zeidler H. Undifferentiated arthritis in an early synovitis out-patient clinic. Clin Exp Rheumatol. 1995 Jan-Feb;13(1):37-43. **PMID:** 7774101 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000001170 - Term: Arthritis, Infectious - ID: D000007239 - Term: Infections - ID: D000025242 - Term: Spondylarthropathies - ID: D000025241 - Term: Spondylarthritis - ID: D000013166 - Term: Spondylitis - ID: D000013122 - Term: Spinal Diseases - ID: D000001847 - Term: Bone Diseases - ID: D000094025 - Term: Post-Infectious Disorders - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC01 - Name: Infections - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4476 - Name: Arthritis - Relevance: HIGH - As Found: Arthritis - ID: M4480 - Name: Arthritis, Rheumatoid - Relevance: HIGH - As Found: Arthritis, Rheumatoid - ID: M16362 - Name: Synovitis - Relevance: HIGH - As Found: Synovitis - ID: M19262 - Name: Arthritis, Reactive - Relevance: HIGH - As Found: Arthritis, Reactive - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M4478 - Name: Arthritis, Infectious - Relevance: LOW - As Found: Unknown - ID: M23036 - Name: Spondylarthropathies - Relevance: LOW - As Found: Unknown - ID: M15961 - Name: Spondylitis - Relevance: LOW - As Found: Unknown - ID: M23035 - Name: Spondylarthritis - Relevance: LOW - As Found: Unknown - ID: M15919 - Name: Spinal Diseases - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M3014 - Name: Post-Infectious Disorders - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T5554 - Name: Synovitis - Relevance: HIGH - As Found: Synovitis - ID: T4887 - Name: Reactive Arthritis - Relevance: HIGH - As Found: Arthritis, Reactive - ID: T5412 - Name: Spondylarthropathy - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000016918 - Term: Arthritis, Reactive - ID: D000001168 - Term: Arthritis - ID: D000001172 - Term: Arthritis, Rheumatoid - ID: D000013585 - Term: Synovitis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06156579 **Acronym:** VenSwitch **Brief Title:** Combination Salvage Therapy With Venetoclax and Decitabine in Relapsed/Refractory AML **Official Title:** Phase II Study of (Early) Combination Salvage Therapy With Venetoclax and in Intensified Decitabine in Relapsed/Refractory AML #### Organization Study ID Info **ID:** VenSwitch #### Organization **Class:** OTHER **Full Name:** University Hospital Tuebingen ### Status Module #### Completion Date **Date:** 2025-03-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-05 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-30 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-04 **Type:** ESTIMATED #### Start Date **Date:** 2023-11-04 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2023-12-05 **Type:** ACTUAL **Study First Submit Date:** 2023-11-13 **Study First Submit QC Date:** 2023-11-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital Tuebingen #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this prospective, phase II single center, one arm, open label clinical trial is to test the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in patients with newly diagnosed AML (acute myeloid leukemia) and primary induction failure and patients with relapse of AML/MDS IB2 (myelodysplastic neoplasm with increased blasts 2) after chemotherapy. The primary endpoint is hematologic remission after treatment with Decitabine and Venetoclax. Participants eligible for the trial will receive a treatment of ten days of Decitabine and twenty-eight days of Venetoclax for one or two cycles, after which hematological remission will be assessed. Follow up will include the first one hundred days after end of treatment. **Detailed Description:** This is a prospective, phase II single center one arm, open label clinical trial testing the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in relapsed or refractory AML and MDS IB2. Enrolled will be twenty-seven patients with newly diagnosed AML and primary induction failure to conventional anthracycline-based induction chemotherapy, as well as patients with a relapse of AML oder MDS IB2 after chemotherapy. Patients will receive a combination therapy of ten days of Decitabine and twenty-eigt days of Venetoclax. If hematologic remission is not achieved after one cycle of treatment, patients receive a second cycle. After treatment, a follow-up period of 100 days will ensue. The main aim of the trial is the assessment of hematologic remission after combining Venetoclax with a time-dense immediate application of the hypomethylating agent Decitabine after failure of a chemotherapy approach, thus additionally altering backbone treatment modalities from chemotherapy to epigenetic and anti-BCL2 (B-cell lymphoma 2) treatment. A first assessment of safety and feasibility will take place after the treatment of three patients and a second assessment for safety, feasibility and efficacy/futility after nine patients. ### Conditions Module **Conditions:** - AML - MDS **Keywords:** - Venetoclax - Decitabine - salvage therapy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** single center, one arm, open label clinical trial ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 27 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Salvage therapy with Venetoclax and intensified Decitabine **Intervention Names:** - Drug: Decitabine - Drug: Venetoclax **Label:** Treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment **Description:** Decitabine 20 mg/m\^2, i.v., once daily, 10 days **Name:** Decitabine **Other Names:** - Dacogen **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Treatment **Description:** Venetoclax, 400 mg, p.o., once daily, 28 days **Name:** Venetoclax **Other Names:** - Venclyxto - Venclexta **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** defined as best response in bone marrow aspiration cytology with \<5% residual bone marrow blasts **Measure:** Rate of hematological remissions **Time Frame:** measured after the first and second cycle (each cycle is 28 days) #### Secondary Outcomes **Description:** evaluated by the incidence of CTCAEs ≥ grade 3 **Measure:** Rate of CTCAEs ≥ grade 3 **Time Frame:** observed during the first and second cycle (each cycle is 28 days) **Description:** hematopoietic recovery defined as absolute neutrophil counts ≥0.5 and ≥1.0 x 109/L; platelets ≥50 and ≥100 x 109/L) **Measure:** Time to hematopoietic recovery in days **Time Frame:** after he first and second cycle (each cycle is 28 days) and the first 100 days after end of treatment **Description:** cytogenetic MRD is evaluated after each cycle of Decitabine/ Venetoclax in those patients with an established MRD-marker **Measure:** Rate of MRD-negativity (measurable residual disease) **Time Frame:** measured after the first and second cycle (each cycle is 28 days) **Description:** evaluated by the incidence of infections requiring i.v. antibiotic treatment (CTCAEs ≥ grade 3) **Measure:** Rate of infectious complications **Time Frame:** measured during the first and second cycle and the first 28 days after end of treatment (each cycle is 28 days) **Description:** defined as days from diagnosis of primary induction failure or relapse to infusion of allogeneic hematopoietic stem cells **Measure:** Time to transplant in days **Time Frame:** until day 100 after end of treatment **Description:** defined as rate of patients alive without hematological progression at day 100 after end of treatment **Measure:** Progression-free survival **Time Frame:** day 100 after end of treatment **Description:** defined as rate of patients alive at day 100 after end of treatment **Measure:** Overall survival **Time Frame:** day 100 after end of treatment **Description:** Defined patients non longer alive at day 30 after start of treatment **Measure:** Early Mortality **Time Frame:** day 30 after start of treatment **Description:** evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) at screening, and at the end of cycle one and two, as well as at follow up; scale scores ranging from 0 to 100 with higher scores indicating better outcomes **Measure:** Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30)) **Time Frame:** at screening and at the end of cycle one and two (one cycle is 28 days) and at follow up (day 100 after end of treatment) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Diagnosis of AML according to WHO (world health organization) criteria regardless of subtype a. Including de novo and transformed MPN (myeloproliferative neoplasm) and transformed MDS 2. Refractory to induction chemotherapy consisting of Daunorubicin+Cytarabine ("3+7") based chemotherapy, including CPX351, including combination with the FLT3- inhibitor (fms-like tyrosine kinase) Midostaurin or Mylotarg, defined as 1. ≥5% medullary blasts in bone marrow assessments after first cycle of induction chemotherapy 3. Relapse of AML/MDS IB2 after chemotherapy (≥5% medullary blasts in bone marrow assessment) 4. Must be ≥ 18 years at the time of signing the informed consent. 5. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. 6. Able to adhere to the study visit schedule and other protocol requirements. 7. Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist 8. No known history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) \>40% (adjusted for hemoglobin, if available) and FEV1/FVC \>50% (Forced expiratory volume in one second/ forced vital capacity) 9. Subject (male or female (FCBP))1 is willing to use highly effective birth control methods during treatment and for 3 months (male) and 6 months (female) after the end of treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system bilateral tubal occlusion, vasectomized partner, sexual abstinence). Female subjects who use hormonal contraceptives should also use a barrier method. <!-- --> 1. A FCBP is defined as any female who does not meet the criteria of non childbearing potential. These are as follows: * documented hysterectomy, bilateral oophorectomy (ovariectomy), or bilateral tubal ligation * post-menopausal (a practical definition accepts menopause ≥ 1 year without menses with an appropriate clinical profile, e.g. age \> 45 years in the absence of hormone replacement therapy (HRT). In questionable cases, the subject must have a follicle stimulating hormone (FSH) value \> 40 mIU/ml and an estradiol value \< 40pg/ml. 2. Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success 3. In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 10. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment. 11. All subjects must agree not to share medication. Exclusion Criteria: 1. Acute Promyelocytic Leukemia (AML with t (15;17)) 2. Not consenting to chemotherapy in general 3. Previous Treatment with allogeneic stem cell transplantation 4. ECOG \>3 (Eastern Cooperative Oncology Group) 5. Medical History of hypersensitivity to to the active substances of Venetoclax and Decitabine or to any of the excipients listed in the respective SmPCs (summary of product characteristics) 6. Women during pregnancy and lactation. 7. Significant active cardiac disease within 6 months prior to the start of study treatment, including: • New York Heart Association (NYHA) class III or IV congestive heart failure; • Myocardial infarction; • Unstable angina and/or stroke; * Severe cardiac arrhythmias * Left ventricular ejection fraction (LVEF) \<40% by ultrasound obtained within 28 days prior to the start of study treatment. 8. Severe obstructive or restrictive ventilation disorder 9. Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. (Note: Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening) 10. Active infection, including hepatitis B or hepatitis C antibody or Human Immunodeficiency Virus (HIV) infection, that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or which could expose the patient to undue risk through the participation in the clinical trial; an infection controlled with an approved antibiotic/ antiviral/ antifungal treatment that is not a strong or moderate CYP3A (cytochrome P450) inducer is allowed. 11. Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation 12. Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs 13. Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at \<30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed: • Basal or squamous cell carcinoma of the skin; * Carcinoma in situ of the cervix; * Carcinoma in situ of the breast; * Incidental histologic finding of prostate cancer 14. Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: patients, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy). **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** lucas.mix@med.uni-tuebingen.de **Name:** Lucas Mix, Dr. **Phone:** (+49)70712961781 **Role:** CONTACT #### Locations **Location 1:** **City:** Tuebingen **Contacts:** ***Contact 1:*** - **Email:** lucas.mix@med.uni-tuebingen.de - **Name:** Lucas Mix, Dr. - **Phone:** (+49)70712961781 - **Role:** CONTACT ***Contact 2:*** - **Name:** Claudia Lengerke, Prof. - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Wolfgang Bethge, Prof. - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Wichard Vogel, Prof. - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Lucas Mix, Dr. - **Role:** SUB_INVESTIGATOR **Country:** Germany **Facility:** University Hospital **State:** Baden-Wuerttemberg **Status:** RECRUITING **Zip:** 72076 #### Overall Officials **Official 1:** **Affiliation:** University Hospital Tuebingen **Name:** Claudia Lengerke, Prof. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1697 - Name: Decitabine - Relevance: HIGH - As Found: Above - ID: M249656 - Name: Venetoclax - Relevance: HIGH - As Found: Third - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000579720 - Term: Venetoclax - ID: D000077209 - Term: Decitabine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01767779 **Brief Title:** Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC **Official Title:** Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC #### Organization Study ID Info **ID:** 1P20NS080199-01 **Link:** https://reporter.nih.gov/quickSearch/1P20NS080199-01 **Type:** NIH #### Organization **Class:** OTHER **Full Name:** University of Alabama at Birmingham ### Status Module #### Completion Date **Date:** 2018-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-04-11 **Type:** ACTUAL **Last Update Submit Date:** 2019-04-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-12 **Type:** ACTUAL #### Start Date **Date:** 2012-09 **Status Verified Date:** 2019-04 #### Study First Post Date **Date:** 2013-01-14 **Type:** ESTIMATED **Study First Submit Date:** 2013-01-07 **Study First Submit QC Date:** 2013-01-10 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Children's Hospital Medical Center, Cincinnati **Class:** OTHER **Name:** The University of Texas Health Science Center, Houston **Class:** OTHER **Name:** University of California, Los Angeles **Class:** OTHER **Name:** Boston Children's Hospital #### Lead Sponsor **Class:** OTHER **Name:** University of Alabama at Birmingham #### Responsible Party **Investigator Affiliation:** University of Alabama at Birmingham **Investigator Full Name:** Martina Bebin **Investigator Title:** Associate Professor of Neurology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** To determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial. Since not all patients with TSC develop epilepsy, it would be useful to have a biomarker that could predict those patients destined to have epilepsy and thus identify those TSC patients most appropriate for an antiepileptogenic drug trial. A recent study suggests that treating TSC patients with an abnormal EEG prior to onset of infantile spasms with vigabatrin may improve neurological outcome, but the use of EEG as a reliable biomarker of future epilepsy has not been rigorously validated. In this specific aim, we will test the reliability of EEG in predicting future development of infantile spasms or epilepsy in TSC patients during the first year of life. **Detailed Description:** Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease progression. In recent years, there have been tremendous interest and effort by basic scientists and clinicians in epilepsy in developing disease-modifying or "antiepileptogenic" therapies. However, these efforts are hindered by a couple significant limitations: 1) difficulty in identifying an appropriate high-risk patient population in which a preventative approach is feasible and justifiable, and 2) lack of appropriate drug targets with antiepileptogenic properties. Tuberous Sclerosis Complex (TSC) is one of the most common genetic causes of epilepsy and a subset of TSC patients may represent a rational, feasible population to target with an antiepileptogenic approach for several reasons. First of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due to non-neurological findings - thus, it is feasible to identify these patients and initiate a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these patients are at high risk for developing epilepsy (\~80%) in the future, including infantile spasms (\~35%), a particularly devastating type of childhood epilepsy with a poor prognosis - thus, initiating a therapy with potential side effects in a pre-symptomatic stage can likely be justified in TSC patients. Finally, the identification of the mTOR pathway in the pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties in TSC, as already supported by pre-clinical animal studies - thus, a rational mechanistically-based treatment potentially already exists and can be readily tested in TSC patients. However, there may be significant risks and side effects of mTOR inhibitors, especially during early childhood, such as chronic immunosuppression and theoretical effects on learning, growth, and development. Thus, before initiating an antiepileptogenic drug trial in TSC patients, it would be beneficial to obtain further evidence to optimize the selection criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR inhibitors. The aim of this clinical trial is to determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial. ### Conditions Module **Conditions:** - Tuberous Sclerosis Complex **Keywords:** - Epilepsy - TSC - Tuberous Sclerosis Complex - Infants - Seizures - Biomarkers - EEG ### Design Module #### Bio Spec **Description:** A single venous blood sample will be drawn from the child and parents/family guardian for future research studies and future genetic testing **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC **Label:** seizure free infants with dx of TSC #### Arm Group 2 **Description:** Parent or family guardian of infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC. **Label:** Parents or family guardian of cohort 1 ### Outcomes Module #### Primary Outcomes **Description:** Physical/neurological exam, Video EEG, Developmental assessments, Blood draw from child and parents/guardian, and Seizure diaries. **Measure:** Identification of EEG biomarkers as predictors of developing epilepsy in infants with Tuberous Sclerosis Complex **Time Frame:** 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Cohort 1 * \< 6 months of age; Seizure free at the time of study enrollment; and meets genetic or clinical diagnostic criteria for TSC (Tuberous Sclerosis), the latter based on current recommendations for diagnostic evaluation, such as physical exam, neuroimaging, echocardiogram. Cohort 2 * Parent or family guardian of infant Exclusion Criteria: Cohort 1 * ≥ 6months of age; history of seizures and/or infantile spasms; patients receiving vigabatrin or any anti-epileptic medication or mTOR inhibitor prior to study enrollment Cohort 2 * not parent or family guardian **Maximum Age:** 6 Months **Minimum Age:** 1 Day **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** Infants that are seizure free at the time of the study enrollment and meets genetic or clinical diagnostic criteria for TSC (determined as standard of care); parent/family guardian health status is unknown ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham **State:** Alabama **Zip:** 35294 **Location 2:** **City:** Los Angeles **Country:** United States **Facility:** UCLA **State:** California **Zip:** 90095 **Location 3:** **City:** Boston **Country:** United States **Facility:** Boston Children's Hospital **State:** Massachusetts **Zip:** 02115 **Location 4:** **City:** Cincinnati **Country:** United States **Facility:** Cincinnati Children's Hospital **State:** Ohio **Zip:** 45229 **Location 5:** **City:** Houston **Country:** United States **Facility:** University of Texas in Houston **State:** Texas **Zip:** 77030 #### Overall Officials **Official 1:** **Affiliation:** University of Alabama at Birmingham **Name:** Martina Bebin, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006222 - Term: Hamartoma - ID: D000009369 - Term: Neoplasms - ID: D000009378 - Term: Neoplasms, Multiple Primary - ID: D000009386 - Term: Neoplastic Syndromes, Hereditary - ID: D000065703 - Term: Malformations of Cortical Development, Group I - ID: D000054220 - Term: Malformations of Cortical Development - ID: D000009421 - Term: Nervous System Malformations - ID: D000020752 - Term: Neurocutaneous Syndromes - ID: D000020271 - Term: Heredodegenerative Disorders, Nervous System - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000000013 - Term: Congenital Abnormalities - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M7983 - Name: Epilepsy - Relevance: HIGH - As Found: Epilepsy - ID: M15452 - Name: Seizures - Relevance: LOW - As Found: Unknown - ID: M17152 - Name: Tuberous Sclerosis - Relevance: HIGH - As Found: Tuberous Sclerosis - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M9314 - Name: Hamartoma - Relevance: LOW - As Found: Unknown - ID: M12323 - Name: Neoplasms, Multiple Primary - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M12331 - Name: Neoplastic Syndromes, Hereditary - Relevance: LOW - As Found: Unknown - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M27589 - Name: Malformations of Cortical Development - Relevance: LOW - As Found: Unknown - ID: M12365 - Name: Nervous System Malformations - Relevance: LOW - As Found: Unknown - ID: M22509 - Name: Neurocutaneous Syndromes - Relevance: LOW - As Found: Unknown - ID: M22092 - Name: Heredodegenerative Disorders, Nervous System - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: T5751 - Name: Tuberous Sclerosis Complex - Relevance: HIGH - As Found: Tuberous Sclerosis Complex ### Condition Browse Module - Meshes - ID: D000014402 - Term: Tuberous Sclerosis - ID: D000004827 - Term: Epilepsy - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01241279 **Brief Title:** Accommodation Measurements After Bilateral Implantation of an Aspheric Accommodating Lens and Monofocal Aspheric Lenses **Official Title:** A Two Arm Prospective, Randomized, Double-Masked Clinical Evaluation of Accommodation Measurements After Bilateral Implantation of an Aspheric Accommodating Lens and Monofocal Aspheric Lenses #### Organization Study ID Info **ID:** 657 #### Organization **Class:** INDUSTRY **Full Name:** Bausch & Lomb Incorporated ### Status Module #### Completion Date **Date:** 2011-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-11-26 **Type:** ESTIMATED **Last Update Submit Date:** 2014-11-25 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2011-11 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-11-26 **Type:** ESTIMATED **Results First Submit Date:** 2013-05-17 **Results First Submit QC Date:** 2014-11-25 #### Start Date **Date:** 2010-10 **Status Verified Date:** 2014-11 #### Study First Post Date **Date:** 2010-11-16 **Type:** ESTIMATED **Study First Submit Date:** 2010-11-12 **Study First Submit QC Date:** 2010-11-12 **Why Stopped:** Terminated due to low enrollment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Bausch & Lomb Incorporated #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of this study is to demonstrate the correlation of near vision and changes in higher order aberrations following lens extraction and to characterize the defocus curves of Crystalens® AO™ intraocular lens (IOL) versus the monofocal aspheric SofPort® LI61AO IOL in adults. ### Conditions Module **Conditions:** - Cataract **Keywords:** - cataract surgery - intraocular lens ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 6 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A silicone multi-piece accommodating intraocular lens **Intervention Names:** - Device: Crystalens AO **Label:** Crystalens AO **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** A silicone multi-piece foldable aspheric intraocular lens **Intervention Names:** - Device: SoftPort LI61AO **Label:** SoftPort LI61AO **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Crystalens AO **Description:** Participants will undergo small incision cataract surgery (phacoemulsification). At the time of surgery, eligible participants will be implanted bilaterally with the Crystalens AO intraocular lens. **Name:** Crystalens AO **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - SoftPort LI61AO **Description:** Participants will undergo small incision cataract surgery (phacoemulsification). At the time of surgery, eligible participants will be implanted bilaterally with the SoftPort LI61AO intraocular lens. **Name:** SoftPort LI61AO **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The measurement of optical change in the power of the eye when viewing from far to near. Accommodation decreases as age increases resulting in an inability to focus on near objects. **Measure:** Amplitude of Accommodation **Time Frame:** Visit 4 (postoperative day 120-180) #### Secondary Outcomes **Description:** Number of correct letters on an early treatment diabetic retinopathy study (ETDRS) chart to measure distance visual acuity and the smallest readable print size on an Minnesota Low-Vision Reading (MNREAD) acuity chart for intermediate and near visual acuity (VA). Visual acuity measured in LogMAR. **Measure:** Visual Acuity **Time Frame:** All visits through visit 4 (day 160-180) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects must have clear intraocular media other than cataract. * Subjects must have a clinically documented diagnosis of age-related bilateral cataracts that are considered amenable to treatment with standard phacoemulsification cataract extraction. * Subjects must be undergoing primary IOL implantation for the correction of aphakia following central continuous curvilinear anterior capsulorrhexis and phacoemulsification cataract extraction. * Subjects must require a spherical lens power from 10.00 D to 30.00 D. * Subjects must be willing and able to return for all scheduled follow-up examinations for each eye from days 1 through 180 following surgery. * Subjects must have ≤ 1.25 D of preoperative corneal astigmatism. Exclusion Criteria: * Subjects with corneal pathology potentially affecting topography. * Subjects whose fundus cannot be assessed preoperatively. * Subjects with diagnoses of degenerative visual disorders (eg, macular degeneration, or other retinal disorders) that cause potential acuity losses to a level worse than 20/30 as verified by OCT. * Subjects with conditions with increased risk of zonular rupture, such as pseudoexfoliation syndrome. * Subjects who have any active inflammation or edema (swelling) of the cornea, including but not limited to the following: keratitis, keratoconjunctivitis, and keratouveitis. * Subjects with uncontrolled glaucoma. * Subjects with previous retinal detachment. * Subjects with visually significant diabetic retinopathy (proliferative or non-proliferative) which reduces potential acuity to 20/30 or worse. * Subjects with rubella, bilateral congenital, traumatic, complicated or polar cataract. * Subjects with marked microphthalmos or aniridia. * Subjects who have had previous corneal surgery. * Subjects with irregular corneal astigmatism. * Subjects with amblyopia which reduces potential acuity to worse than 20/30. * Subjects with optic atrophy. * Subjects with iris neovascularization. * Subjects with clinically significant retinal pigment epithelium/macular changes which reduces potential acuity to 20/30 or worse. * Subjects with chronic use of systemic steroids or immunosuppressive medications. * Subjects lacking intact binocular vision. **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Irvine **Country:** United States **Facility:** Bausch & Lomb **State:** California **Zip:** 92618 #### Overall Officials **Official 1:** **Affiliation:** Valeant Pharmaceuticals/Bausch & Lomb Incorporated **Name:** Johnson Varughese **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Crystalens AO **Description:** A silicone multi-piece accommodating intraocular lens **ID:** EG000 **Other Num at Risk:** 4 **Serious Number At Risk:** 4 **Title:** Crystalens AO **Group ID:** EG001 **Title:** SoftPort LI61AO **Description:** A silicone multi-piece foldable aspheric intraocular lens **ID:** EG001 **Other Num at Risk:** 2 **Serious Number At Risk:** 2 **Title:** SoftPort LI61AO **Frequency Threshold:** 1 **Time Frame:** 180 days ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 4 **Group ID:** BG001 **Value:** 2 **Group ID:** BG002 **Value:** 6 **Units:** Participants ### Group **ID:** BG000 **Title:** Crystalens AO **Description:** A silicone multi-piece accommodating intraocular lens ### Group **ID:** BG001 **Title:** SoftPort LI61AO **Description:** A silicone multi-piece foldable aspheric intraocular lens ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 6 **Class Title:** Age 54 to 70 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** NUMBER **Title:** Age, Customized **Unit of Measure:** participants ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** Study data generated as a result of this study will be regarded as confidential, until appropriate analysis and review by the Sponsor or its designee and the Investigator(s) are completed. The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Limitations and Caveats **Description:** Study terminated early due to lack of enrollment ### Point of Contact **Email:** Johnson.Varughese@valeant.com **Organization:** Valeant Pharmaceuticals/Bausch & Lomb **Phone:** 908-927-1162 **Title:** Johnson Varughese ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 #### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The measurement of optical change in the power of the eye when viewing from far to near. Accommodation decreases as age increases resulting in an inability to focus on near objects. **Population Description:** DUE TO THE SMALL SAMPLE SIZE, NO STATISTICAL OR CLINICALLY MEANINGFUL CONCLUSIONS RELATED TO THE STUDY ENDPOINTS CAN BE MADE. **Reporting Status:** POSTED **Time Frame:** Visit 4 (postoperative day 120-180) **Title:** Amplitude of Accommodation **Type:** PRIMARY ##### Group **Description:** A silicone multi-piece accommodating intraocular lens **ID:** OG000 **Title:** Crystalens AO ##### Group **Description:** A silicone multi-piece foldable aspheric intraocular lens **ID:** OG001 **Title:** SoftPort LI61AO #### Outcome Measure 2 **Description:** Number of correct letters on an early treatment diabetic retinopathy study (ETDRS) chart to measure distance visual acuity and the smallest readable print size on an Minnesota Low-Vision Reading (MNREAD) acuity chart for intermediate and near visual acuity (VA). Visual acuity measured in LogMAR. **Population Description:** DUE TO THE SMALL SAMPLE SIZE, NO STATISTICAL OR CLINICALLY MEANINGFUL CONCLUSIONS RELATED TO THE STUDY ENDPOINTS CAN BE MADE. **Reporting Status:** POSTED **Time Frame:** All visits through visit 4 (day 160-180) **Title:** Visual Acuity **Type:** SECONDARY ##### Group **Description:** A silicone multi-piece accommodating intraocular lens **ID:** OG000 **Title:** Crystalens AO ##### Group **Description:** A silicone multi-piece foldable aspheric intraocular lens **ID:** OG001 **Title:** SoftPort LI61AO ### Participant Flow Module #### Group **Description:** A silicone multi-piece accommodating intraocular lens **ID:** FG000 **Title:** Crystalens AO #### Group **Description:** A silicone multi-piece foldable aspheric intraocular lens **ID:** FG001 **Title:** SoftPort LI61AO #### Period **Title:** Overall Study ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 **Pre-Assignment Details:** Due to the small sample size, NO STATISTICAL OR CLINICALLY MEANINGFUL CONCLUSIONS RELATED TO THE STUDY ENDPOINTS CAN BE MADE. **Recruitment Details:** A total of 6 subjects (11 eyes) were enrolled at one investigational site in the US. First participant enrolled 10/26/2010; last participant visit 12/01/2011. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04993079 **Acronym:** CLOTOUT **Brief Title:** Clotild® Smart Guidewire System (CSGS) Evaluation in EndovascUlar Thrombectomy Procedure **Official Title:** Clotild® Smart Guidewire System Evaluation in Endovascular Thrombectomy Procedure #### Organization Study ID Info **ID:** SEN_CLOTILD_FIH_1 #### Organization **Class:** INDUSTRY **Full Name:** Sensome ### Status Module #### Completion Date **Date:** 2024-04-13 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ESTIMATED **Last Update Submit Date:** 2024-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-04-13 **Type:** ACTUAL #### Start Date **Date:** 2021-08-26 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2021-08-06 **Type:** ACTUAL **Study First Submit Date:** 2020-09-01 **Study First Submit QC Date:** 2021-08-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sensome #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this First-in-Human study is to evaluate the safety of using the Clotild® system to guide the endovascular thrombectomy (EVT) device to the clot location during EVT for the treatment of an acute ischemic stroke eligible to EVT, whatever the EVT device chosen. A secondary purpose is to assess the clinical performance, defined as the feasibility of measuring clot electrophysiological parameters in vivo during EVT procedures. **Detailed Description:** Clotild® is a neurovascular guidewire equipped with the Sensome proprietary impedance sensor. The latter allows the measurement of the electrophysiological characteristics of the surrounding tissues. Clotild® could categorize the thrombus occluding the cerebral blood vessel, and support the neurointerventionist during mechanical thrombectomy for the treatment of ischemic stroke. The aim of the study is to evaluate the safety and the performance of the device. The electrophysiological measurements will be used to update Clotild®'s database and thus improve the prediction accuracy of the model in providing physicians with insights for mechanical thrombectomy. ### Conditions Module **Conditions:** - Stroke ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 41 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects presenting an acute ischemic stroke due to M1 or middle cerebral artery (MCA) bifurcation occlusion, eligible for Endovascular Thrombectomy (EVT) based on neuro-interventionist and/or neurologist investigators' opinion will be eligible. Twenty (20) patients will be initially enrolled. Up to 42 patients will be enrolled following an analysis of the data of the first 20 enrolled patients by a data safety monitoring board (DSMB) and its' recommendation to proceed with the study. Clots will be retrieved and analysed in a group of participants for which Clotild® is used as neurovascular guidewire. **Intervention Names:** - Device: Clotild® **Label:** Clotild® **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Clotild® **Description:** Use of Clotild® as neurovascular guidewire **Name:** Clotild® **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Tthe proportion of patients having intracranial vessel perforation and / or dissection due to Clotild® usage at the site of usage in intracranial vessels will be assessed by Interventional Neuroradiologist during the procedure and final adjudication of the DSA (Digital Subtraction Angiography) by the Data Safety Monitoring Board. **Measure:** The proportion of patients having intracranial vessel perforation and / or dissection due to Clotild® usage at the site of usage in intracranial vessels **Time Frame:** Measured during the procedure **Description:** The ability to perform binary classification of individual electrophysiological parameter measurements will be assessed by distinguishing local regions with substantial red blood cell content (RBC-rich) from regions with negligible red blood cell content (RBC-poor) in the occlusion. **Measure:** The ability to perform binary classification of individual electrophysiological parameter measurements **Time Frame:** Measured during the procedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke eligible for EVT 2. M1 and/or MCA bifurcation arterial occlusion on Computed tomography angiography (CTA) or MRA (Magnetic resonance angiography) of an intracranial vessel amenable to EVT 3. Informed Consent by subject, subject's Legally Authorized Representative (LAR) or anyone approved by the Ethics Committee (EC) and/or regulatory agencies to provide consent on behalf of the subject. Exclusion Criteria: 1. Patient having an intracranial occlusion other than M1 and/or MCA bifurcation, especially tandem occlusion and ICA (internal carotid artery) occlusion. 2. Current participation in another investigational device or drug study that has not completed the primary endpoint or that clinically interferes with the current study endpoints 3. Candidates not eligible for EVT based on neurointerventionist and/or neurologist investigators' opinion 4. Pregnancy or lactating subjects **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Liverpool **Country:** Australia **Facility:** Liverpool Hospital **State:** New South Wales **Zip:** NSW 2170 **Location 2:** **City:** Southport **Country:** Australia **Facility:** Gold Coast University Hospital **State:** Queensland **Zip:** QL 5215 **Location 3:** **City:** Limoges **Country:** France **Facility:** CHU Limoges **Zip:** 87000 #### Overall Officials **Official 1:** **Affiliation:** Liverpool Hospital, Liverpool NSW, Australia **Name:** Andrew Cheung, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Liverpool Hospital, Liverpool NSW, Australia **Name:** Dennis Cordato, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M22306 - Name: Stroke - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02577679 **Brief Title:** Associations Between Periodontitis and Autoimmune Antibodies in Rheumatoid Arthritis Disease **Official Title:** Associations Between Periodontitis and Autoimmune Antibodies in Rheumatoid Arthritis Disease #### Organization Study ID Info **ID:** 201503116RINA #### Organization **Class:** OTHER **Full Name:** National Taiwan University Hospital ### Status Module #### Completion Date **Date:** 2015-11 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2015-10-16 **Type:** ESTIMATED **Last Update Submit Date:** 2015-10-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2015-09 **Type:** ACTUAL #### Start Date **Date:** 2015-06 **Status Verified Date:** 2015-10 #### Study First Post Date **Date:** 2015-10-16 **Type:** ESTIMATED **Study First Submit Date:** 2015-09-23 **Study First Submit QC Date:** 2015-10-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** National Taiwan University Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this case control study is to explore the possible association between periodontal destruction and serum anti-CCP antibodies in RA patients and healthy subjects. **Detailed Description:** In patients with RA, the anti-CCP antibody titer seems positively correlated to their periodontal destruction and disease activity in comparison with healthy subjects. ### Conditions Module **Conditions:** - Periodontitis, Rheumatoid Arthritis, Autoimmunity, **Keywords:** - Dentistry ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 47 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Lower then 7 Unit/milliliter: negative 7-10 Unit/milliliter: weak positive Higher then 10 Unit/milliliter: positive **Measure:** Serum level of anti-cyclic citrullinated peptide/protein antibody **Time Frame:** Base line **Description:** Lower then 4 millimeter: normal Higher then 4 millimeter: diseased/previously diseased **Measure:** Periodontal pocket depth and clinical attachment level **Time Frame:** Baseline #### Secondary Outcomes **Description:** Recorded in picogram per milliliter **Measure:** Serum level of tumor necrotic factor alpha **Time Frame:** Baseline **Description:** Recorded in Unit per milliliter **Measure:** Serum level of anti-mutated citrullinated vimentin **Time Frame:** Baseline **Description:** Recorded in picogram per milliliter **Measure:** Serum level of interleukin 6 **Time Frame:** Baseline **Description:** Recorded in picogram per milliliter **Measure:** Serum level of interleukin 17 **Time Frame:** Baseline ### Eligibility Module **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 60 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Physically healthy persons, especially free of any autoimmune diseases, DM, CVD. No history of periodontal treatment. ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei **Country:** Taiwan **Facility:** National Taiwan University Hospital **Zip:** 100 #### Overall Officials **Official 1:** **Affiliation:** Assistant professor **Name:** Yi-Wen Chen, PhD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000010510 - Term: Periodontal Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M13427 - Name: Periodontitis - Relevance: HIGH - As Found: Periodontitis - ID: M4476 - Name: Arthritis - Relevance: HIGH - As Found: Arthritis - ID: M4480 - Name: Arthritis, Rheumatoid - Relevance: HIGH - As Found: Rheumatoid Arthritis - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M13419 - Name: Periodontal Diseases - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001168 - Term: Arthritis - ID: D000001172 - Term: Arthritis, Rheumatoid - ID: D000010518 - Term: Periodontitis ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4625 - Name: Autoantibodies - Relevance: LOW - As Found: Unknown - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00827879 **Brief Title:** Strength at Home Couples Program (PTSD-Focused Relationship Enhancement Therapy for Returning Veterans) **Official Title:** Strength at Home Couples Program (Formerly: PTSD-Focused Relationship Enhancement Therapy for Returning Veterans and Their Partners) #### Organization Study ID Info **ID:** U49CE001248 **Link:** https://reporter.nih.gov/quickSearch/U49CE001248 **Type:** NIH #### Organization **Class:** OTHER **Full Name:** Boston VA Research Institute, Inc. ### Status Module #### Completion Date **Date:** 2014-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-07-12 **Type:** ACTUAL **Last Update Submit Date:** 2017-07-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-10 **Type:** ACTUAL #### Start Date **Date:** 2009-02 **Status Verified Date:** 2017-07 #### Study First Post Date **Date:** 2009-01-23 **Type:** ESTIMATED **Study First Submit Date:** 2009-01-22 **Study First Submit QC Date:** 2009-01-22 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** Centers for Disease Control and Prevention #### Lead Sponsor **Class:** OTHER **Name:** Boston VA Research Institute, Inc. #### Responsible Party **Investigator Affiliation:** Boston VA Research Institute, Inc. **Investigator Full Name:** Casey Taft **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of the project is to develop and test a couples-based relationship enhancement group intervention for married or partnered Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans to prevent the perpetration of intimate partner aggression (IPA) among participants. **Detailed Description:** The focus of this project is to produce a well-defined and standardized intervention, labeled Strength at Home Couples Group, that can improve intimate relationship satisfaction, decrease the likelihood of relationship aggression, increase the intimacy and closeness of the relationship, and help with anger management. We hope to learn more about how to improve relationships, how to prevent anger and violence, and about what factors help people successfully complete treatment. Strength at Home Couples Group will incorporate components of several interventions for PTSD and IPA and will target mechanisms implicated in the PTSD-IPA association. The development of this type of integrated intervention is critical due to high rates of PTSD-IPA co-occurrence and the pressing need to efficiently address both problems among military veterans. Specific aims of this project are: (1) to develop and standardize Strength at Home Couples Group for male combat veterans, including the development of a clinician-friendly intervention manual detailing Strength at Home Couples Group, along with intervention adherence measures and therapist training and certification procedures; (2) to test the efficacy of Strength at Home Couples Group for OEF/OIF/OND veterans by conducting a multiple site randomized trial comparing 10 sessions of Strength at Home Couples Group to 10 sessions of a supportive group therapy (ST) condition; and (3) to explore differences in compliance and process factors across conditions. ### Conditions Module **Conditions:** - Aggression - Post Traumatic Stress Disorders **Keywords:** - Intimate partner aggression - Couples intervention - PTSD - Veterans - Prevention - Violence Prevention - Prevention of pertetration of intimate partner aggression. ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 156 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** PTSD-Focused Cognitive Behavioral Therapy for Couples **Intervention Names:** - Behavioral: Strength at Home Couples Group **Label:** Strength at Home Couples Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Supportive therapy for couples **Intervention Names:** - Behavioral: Supportive Group Therapy **Label:** Supportive Group Therapy **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Strength at Home Couples Group **Description:** A multiple site randomized trial will compare 10 sessions of PF-RET to 10 sessions of a supportive group therapy. PF-RET focuses on 1) deployment stress and traumatic experiences impacting intimate relationships; 2) communication between intimate partners; 3) conflict and anger management; and 4) closeness and intimacy. **Name:** Strength at Home Couples Group **Other Names:** - PTSD-Focused Relationship Enhancement Therapy - Returning Veterans and Partners **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Supportive Group Therapy **Description:** A general support group designed to enhance support for healthy relationship building. **Name:** Supportive Group Therapy **Other Names:** - Psychological/Behavioral Placebo Control **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** Evidence of change in incidence and frequency of intimate partner physical assault and psychological aggression assessed by questionnaires and clinical interviews. **Time Frame:** Change determined by assessments pre and post treatment, 6 months, 12 months, and 18 months following treatment #### Secondary Outcomes **Measure:** Evidence of change in risk factors (i.e. PTSD symptoms, anger, relationship satisfaction) implicated in the development of IPA assessed by questionnaires, clinical interviews, and psychophysiological measurements. **Time Frame:** Change determined by assessments pre and post treatment, 6 months, 12 months, and 18 months following treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * couples must have been in a committed relationship for at least six months * veterans and their partners must be over the age of 18 * male members of the couple report no occurrence of physical aggression during the last six months in their current relationship on the Revised Conflict Tactics Scale (CTS2; Straus et al, 1996) * female members of the couple may report that they have engaged in low level aggression during the past six months in their current relationship on the Revised Conflict Tactics Scale (CTS2; Straus et al., 1996) * one partner of the couple averages at or below a score of 29 on the 6-item Quality of Marriage Index (QMI; Norton, 1983) or a 100 or below on the Dyadic Adjustment Score (DAS; Spanier, 1976), which are cutoff scores often used to distinguish distressed and non-distressed couples (e.g., Slep, Heyman, Williams, Van Dyke, \& O'Leary, 2006), or one member of the couple endorses veteran-perpetrated psychological aggression (defined as scoring above the 75%ile on the CTS2 minor psychological aggression subscale, or any endorsement of items on the severe psychological aggression subscale on the CTS2 or the Dominance/Intimidation scale of the Multidimensional Measure of Emotional Abuse, MMEA; Murphy \& Hoover, 1999;) * both members of the couple provide research consent Exclusion Criteria: * reading difficulties prevent valid completion of the assessment instruments * the participant evidences severe organicity or active psychosis * the participant expresses prominent suicidal or homicidal ideation * the participant meets diagnostic criteria for alcohol and/or drug dependence, if not in early full remission or sustained partial remission * female members of the couple report their violence includes the use of weapons during the past six months in their current relationship on the Revised Conflict Tactics Scale (CTS2; Straus et al., 1996) * violence perpetrated by female members of the couple produces injuries in men * male members of the couple indicate they are fearful of the female partner * male members of the couple report they are physically violent in any way during the past six months or severely violent in the past 12 months of their current relationship on the Revised Conflict Tactics Scale (CTS2; Straus et al., 1996) * male members of the couple have had any bruising or injuries inflicted by the female partner during the past six months in their current relationship. Criteria b through d will be assessed using the Mini-International Neuropsychiatric Interview (MINI; Sheehan et al., 1998) and clinical interview **Healthy Volunteers:** True **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** National Center for PTSD, VA Boston Healthcare System **State:** Massachusetts **Zip:** 02130 **Location 2:** **City:** Providence **Country:** United States **Facility:** Providence VA Medical Center **State:** Rhode Island **Zip:** 02908 #### Overall Officials **Official 1:** **Affiliation:** National Center for PTSD, VA Boston Healthcare System **Name:** Casey T Taft, Ph.D. **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Providence VA Medical Center **Name:** Suzannah Creech, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Norton, R. (1983). Measuring marital quality: A critical look at the dependent variable. Journal of Marriage and the Family, 45, 141-151. **Citation:** Straus, M. A., Hamby, S. L., Boney-McCoy, S., & Sugarman, D. B. (1996). The Revised Conflict Tactics Scales (CTS2): Development and preliminary psychometric data. Journal of Family Issues,17, 283-316. **Citation:** Spanier, G. B. (1976). Measuring dyadic adjustment: New scales for assessing the quality of marriage and similar dyads. Journal of Marriage and the Family, 38, 154-28. **Citation:** Murphy CM, Hoover SA. Measuring emotional abuse in dating relationships as a multifactorial construct. Violence Vict. 1999 Spring;14(1):39-53. **PMID:** 10397625 **Citation:** Taft CT, Creech SK, Gallagher MW, Macdonald A, Murphy CM, Monson CM. Strength at Home Couples program to prevent military partner violence: A randomized controlled trial. J Consult Clin Psychol. 2016 Nov;84(11):935-945. doi: 10.1037/ccp0000129. Epub 2016 Sep 5. **PMID:** 27599224 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000068099 - Term: Trauma and Stressor Related Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000096762 - Term: Aberrant Motor Behavior in Dementia - ID: D000001526 - Term: Behavioral Symptoms ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M16103 - Name: Stress Disorders, Post-Traumatic - Relevance: HIGH - As Found: Post Traumatic Stress Disorder - ID: M24916 - Name: Stress Disorders, Traumatic - Relevance: HIGH - As Found: Traumatic Stress Disorder - ID: M3724 - Name: Aggression - Relevance: HIGH - As Found: Aggression - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M222 - Name: Trauma and Stressor Related Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M6904 - Name: Dementia - Relevance: LOW - As Found: Unknown - ID: M3259 - Name: Aberrant Motor Behavior in Dementia - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000040921 - Term: Stress Disorders, Traumatic - ID: D000013313 - Term: Stress Disorders, Post-Traumatic - ID: D000000374 - Term: Aggression ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05574179 **Brief Title:** Comparison of Sedative Effect of Dexmedetomidine and Midazolam for TIVA **Official Title:** Comparison of Sedative Effect of Dexmedetomidine and Midazolam for TIVA in Pediatric Population Undergoing Inguinal Hernia Repair, Randomized Controlled Trial #### Organization Study ID Info **ID:** Sheikh Zayed Medical College #### Organization **Class:** OTHER_GOV **Full Name:** Sheikh Zayed Medical College ### Status Module #### Completion Date **Date:** 2023-10-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-10-10 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-06 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2023-07-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-01-01 **Type:** ESTIMATED **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2022-10-10 **Type:** ACTUAL **Study First Submit Date:** 2022-10-06 **Study First Submit QC Date:** 2022-10-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Sheikh Zayed Medical College #### Responsible Party **Investigator Affiliation:** Sheikh Zayed Medical College **Investigator Full Name:** Barzah Durrani **Investigator Title:** Dr Barzah durrani **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Comparison of sedative effects of dexmedetomidine and midazolam using ramsay sedation scores intraoperatively in children undergoing inguinal hernia repair. **Detailed Description:** a randomized controlled trial to compare the sesative effects of dexmedetomidine and midazolam in pediatric population planned for inguinal herna repair under TIVA in sheikh zayed hospital rahim yar khan. ### Conditions Module **Conditions:** - Choosing Better Drug Option for Sedation in Pediatric Population Intraoperatively ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Inj.midazolam **Intervention Names:** - Drug: Midazolam **Label:** midazola. **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** inj.dexmedetomidine **Intervention Names:** - Drug: Dexmedetomidine injection **Label:** Dexnedetomidine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dexnedetomidine **Description:** Inj precedex 200mcg in 1ml given in stat doses **Name:** Dexmedetomidine injection **Other Names:** - Precidex **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - midazola. **Description:** Inj.midazolam 5mg/5ml given in stat doses **Name:** Midazolam **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Dexmedetomidine is better sedative agent than midazolam in pediatric population **Time Frame:** 25 minutes #### Secondary Outcomes **Measure:** Midazolam is better sedating agent than dexmedetomidine in pediatric population **Time Frame:** 25 minutes **Measure:** Midazolam and dexmedetomidine are equally good sedating agents in pediatric population **Time Frame:** 25 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ASA I and II Age 6 to 12 years Any gender Exclusion Criteria: * ASA III and above Age less than 2 years and above 12 years Congenital heart disease Cardiac arrythmias Congenital abnormalities Respiratory disease Endocrine disorders Mental retardation Organ dysfunction Bleeding disorders Physician or family refusal Previous surgeries Allergy to any drug **Healthy Volunteers:** True **Maximum Age:** 12 Years **Minimum Age:** 6 Years **Sex:** ALL **Standard Ages:** - CHILD ### IPD Sharing Statement Module **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** From synopsis approval till completion of sample size ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9625 - Name: Hernia - Relevance: LOW - As Found: Unknown - ID: M9630 - Name: Hernia, Inguinal - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000058647 - Term: Adrenergic alpha-2 Receptor Agonists - ID: D000000316 - Term: Adrenergic alpha-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000759 - Term: Adjuvants, Anesthesia - ID: D000014151 - Term: Anti-Anxiety Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000018686 - Term: Anesthetics, Intravenous - ID: D000018681 - Term: Anesthetics, General - ID: D000000777 - Term: Anesthetics - ID: D000018757 - Term: GABA Modulators - ID: D000018682 - Term: GABA Agents ### Intervention Browse Module - Browse Branches - Abbrev: Analg - Name: Analgesics - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AdjAn - Name: Adjuvants, Anesthesia - Abbrev: PsychDr - Name: Psychotropic Drugs ### Intervention Browse Module - Browse Leaves - ID: M22662 - Name: Dexmedetomidine - Relevance: HIGH - As Found: Twice daily - ID: M11845 - Name: Midazolam - Relevance: HIGH - As Found: Induction - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3668 - Name: Adrenergic alpha-Agonists - Relevance: LOW - As Found: Unknown - ID: M3673 - Name: Adrenergic Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4089 - Name: Adjuvants, Anesthesia - Relevance: LOW - As Found: Unknown - ID: M16905 - Name: Anti-Anxiety Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M20766 - Name: Anesthetics, Intravenous - Relevance: LOW - As Found: Unknown - ID: M20761 - Name: Anesthetics, General - Relevance: LOW - As Found: Unknown - ID: M20827 - Name: GABA Modulators - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008874 - Term: Midazolam - ID: D000020927 - Term: Dexmedetomidine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04200079 **Acronym:** KCOCO **Brief Title:** Kingston Chronic Obstructive Pulmonary Disease (COPD) Multidimensional Long Term Follow up Cohort **Official Title:** Kingston COPD Cohort #### Organization Study ID Info **ID:** 43105 #### Organization **Class:** OTHER **Full Name:** Queen's University ### Status Module #### Completion Date **Date:** 2030-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2021-09-14 **Type:** ACTUAL **Last Update Submit Date:** 2021-09-07 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2030-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2020-01-14 **Type:** ACTUAL **Status Verified Date:** 2021-09 #### Study First Post Date **Date:** 2019-12-16 **Type:** ACTUAL **Study First Submit Date:** 2019-12-12 **Study First Submit QC Date:** 2019-12-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dr. Juan Pablo de Torres Tajes #### Responsible Party **Investigator Affiliation:** Queen's University **Investigator Full Name:** Dr. Juan Pablo de Torres Tajes **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Background: Chronic Obstructive Pulmonary (COPD) patients are the paradigm of the chronic complex patient. Their follow up can sometimes be difficult and challenging (1). There are patients with recurrent exacerbations that put an enormous burden on health care resources (2). They also have multiple comorbidities (3) that can sometimes make their management difficult. In an attempt to coordinate all these efforts KGH, HDH and Providence Care have numerous essential resources to take care of COPD patients like the nurse navigators, nurse practitioners and the pulmonary rehabilitation program. These programs provide an excellent support to the clinical activity of Respirologists and other health care providers. Rationale: The main rationale for the development of the Kingston COPD cohort is to translate that highly demanding clinical activity in a teaching and research oriented activity that could be used by clinicians, medical students, residents and fellows. Having a guideline complained established protocol in COPD patients that are usually follow at KGH and HDH could help in not only in unified the way COPD patients are seeing (preserving the importance of the personalized approach) but most importantly established a multidimensional (clinical, physiological, radiological, laboratory) database. This could help know not only the results of our clinical activity but also have a long term (\>5yrs) database for clinical research projects in collaboration with national and international research groups. Therefore this proposal is important because it will help translate our busy daily clinical work in a highly productive teaching and research activity. **Detailed Description:** Aims: establish a long term multidimensional follow up of a large COPD cohort of COPD patients in Kingston, Ontario. Specific Objectives: 1. established a simple and easy to apply follow up protocol in COPD patients. 2. Hire a research assistant 3. Set up the database. Data source: Patients included in the present cohort will be those usually follow at the Respirology clinic at Hotel Dieu Hospital in Kingston Ontario. Data elements: this will include clinical, laboratory, physiological and radiological data. Clinical: baseline and yearly evaluation. The following information will be collected and registered: Age, gender, history of prematurity and low weight at birth, maternal smoking during pregnancy, history of infections or wheezing during infancy, pack year history: (age of smoking initiation, years smoking, packs per day, age of quitting if quit), active or former smokers, use of vaping or marihuana?, registration of Comorbidities using the Copd cOmorbidiTy indEx COTE index, use of medications: LABA, LAMA, dual, LABA/ICS, ICS, Roflumilast, Erithromycin, NAC, etc, use of O2 at home: lt/min and duration, CPAP and BiPAP and pressures, degree of dyspnea measure by the Medical Research Council scale, height, weight, Body Mass Index, Free Fat Mass Index determined by electrical bioimpedance, handgrip, abdominal and pelvic girth. Laboratory: baseline and yearly The following information from the patient chart will be collected and registered: CBC (including differential specifically eosinophilia), CRP, baseline alfa 1 AT levels (only baseline), fibrinogen, basal ABG. Physiological information: yearly evaluation The following information will be collected and registered: FEV1, FVC, FEV1/FVC, TLC, IC/TLC, RV/TLC, DLCO, KCO. MIP, MEP, 6MWD with and without O2 in those O2 Sat 90% or lower. In a sample of interest full Cardiopulmonary exercise test. Radiological information: Yearly Low dose chest CT The following information will be registered from the final reports of the chest CT: Emphysema presence, type, extent and localization, PulmArt/Ao diameter ratio measurement, presence of bronchiectasis (type and localization), presence of air trapping, presence (type and localization) of interstitial changes, presence of coronary calcifications, presence of osteoporosis, presence of lung nodules---- Lung cancer. Data storage and identification Data will be stored in an encrypted file behind a firewall in a KGH server. For research purpose patient's information will be anonimized by using a study ID number that will be linked to the CR number of every patient in a different encrypted file. There will be no personal identifiable information during the entire process of each of the proposed studies. Statistical analysis plan The description of the characteristics of the participants will follow the following methodology: qualitative data will be described using relative frequencies. We will use the Kolmogorov-Smirnov test (K-S) to determine if a quantitative variable has a normal distribution. Quantitative data with a normal distribution will be expressed using the mean and the standard deviation (SD). When comparison between groups is planned the following methodological plan will be applied: quantitative data with non-normal distribution will be described with the median and the interquartile range (IQR). Differences will be compared with chi square for qualitative data or student t test and Mann-Whitney U test for quantitative data according to each variable distribution. ### Conditions Module **Conditions:** - COPD - Emphysema ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 400 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 10 Years ### Arms Interventions Module #### Arm Group 1 **Description:** Long term (at least 10 years) multidimensional (clinical, laboratory, physiological and radiological) follow up of chronic Obstructive Pulmonary Disease patients. **Label:** COPD ### Outcomes Module #### Primary Outcomes **Description:** Patients that will die during the follow up period **Measure:** Mortality **Time Frame:** 10 years **Description:** Number of COPD exacerbations per year **Measure:** Exacerbations **Time Frame:** 10 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patients ages between 40-85 years old. 2. Smoking history of at least 10 pack year history 3. Active of former smokers 4. Diagnosis of COPD according to the GOLD definition (4): post bronchodilator spirometry FEV1/FVC ≤0.70, including those with other associated respiratory diseases like asthma, bronchiectasis, stable lung cancer or Interstitial Lung Disease. 5. Ability to perform all study procedures (complete pulmonary function tests, six minute walking test (6MWT) and chest computed tomography) and provide/sign informed consent. Exclusion Criteria: 1. Patients not willing to sign the consent form 2. Patients with a life expectancy of less than 3 yrs. 3. Patients in palliative care. 4. Patients with chronic airway obstruction ie: FEV1/FVC≤0.70 of other etiology and without a smoking history of less than 10 packs year history. 5. Patients unable ort not able to perform the pulmonary function test, the 6MWT or the chest CT. **Maximum Age:** 85 Years **Minimum Age:** 40 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** COPD patients usually followed at a Respirology clinic ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** jpdt@queensu.ca **Name:** Juan P de Torres, MD **Phone:** 613 549 6666 **Phone Ext:** 6905 **Role:** CONTACT **Contact 2:** **Email:** nederalb@gmail.com **Name:** Alberto Neder, MD **Phone:** 613 549 6666 **Phone Ext:** 3198 **Role:** CONTACT #### Locations **Location 1:** **City:** Kingston **Contacts:** ***Contact 1:*** - **Email:** jpdt@queensu.ca - **Name:** Juan P de Torres, MD - **Phone:** 613 549 6666 - **Phone Ext:** 6905 - **Role:** CONTACT **Country:** Canada **Facility:** KHSC **State:** Ontario **Status:** RECRUITING **Zip:** K7L2V6 #### Overall Officials **Official 1:** **Affiliation:** Queen's University **Name:** Juan P de Torres, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Only on specific request **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: M23449 - Name: Pulmonary Disease, Chronic Obstructive - Relevance: LOW - As Found: Unknown - ID: M7812 - Name: Emphysema - Relevance: HIGH - As Found: Emphysema - ID: M14510 - Name: Pulmonary Emphysema - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004646 - Term: Emphysema ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05628779 **Acronym:** TRACE-NL **Brief Title:** Evaluating Edge-to-edge Transcatheter Tricuspid Valve Repair in Patients With Severe Symptomatic Tricuspid Regurgitation **Official Title:** Evaluation of the Safety, Efficacy and Cost-effectiveness of Transcatheter Tricuspid Valve Repair in Patients With Severe Tricuspid Regurgitation in the Netherlands. #### Organization Study ID Info **ID:** NL81645.100.22 #### Organization **Class:** OTHER **Full Name:** St. Antonius Hospital ### Status Module #### Completion Date **Date:** 2027-11-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-16 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-15 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2027-11-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-12-12 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2022-11-29 **Type:** ACTUAL **Study First Submit Date:** 2022-10-27 **Study First Submit QC Date:** 2022-11-16 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** ZonMw: The Netherlands Organisation for Health Research and Development #### Lead Sponsor **Class:** OTHER **Name:** St. Antonius Hospital #### Responsible Party **Investigator Affiliation:** St. Antonius Hospital **Investigator Full Name:** Martin J. Swaans **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a national multicenter, open-label, randomized controlled trial to show superiority of edge-to-edge Transcatheter Tricuspid Valve repair (TTVr) on top of the Standard Of Care (SOC; heart failure medication) over the SOC alone in patients with symptomatic severe Tricuspid Regurgitation (TR) in the Netherlands. **Detailed Description:** Tricuspid valve regurgitation (TR) is a common heart valve disease associated with mortality, heart failure hospitalization (HHF) and a significant negative impact on quality of life (QoL). The prevalence of moderate or severe TR in the Netherlands is estimated at 0.55% and becoming more prevalent. Surgery is rarely performed, because in-hospital mortality is high and there is little evidence for the efficacy. The majority of patients does therefore entirely dependent on treatment with heart failure medication. However, a subset of these patients experience (progressive) symptoms of refractory congestive heart failure despite the SOC with heart failure medication. Transcatheter Tricuspid Valve repair (TTVr) offers several new strategies to address severe TR; one promising technique to treat patients with symptomatic severe TR is edge-to-edge tricuspid valve (TV) repair through leaflet approximation. Edge-to-edge TTVr may provide an elegant alternative treatment for many patients, because it is less burdensome due to the minimally invasive nature. Moreover, multiple single-arm trials already reported promising outcomes in terms of efficacy and safety, and the technique is very similar to Transcatheter Mitral Valve repair (TMVr), with yet proven feasibility, efficacy and safety. The aim of this study is to evaluate the safety, efficacy and cost-effectiveness of TTVr for patients with symptomatic severe TR despite the SOC and high/prohibitive surgical risk in the Netherlands. ### Conditions Module **Conditions:** - Tricuspid Valve Regurgitation, Nonrheumatic - Cardiac Catheterization - Heart Failure, Right Sided - Valve Regurgitation, Tricuspid **Keywords:** - Transcatheter tricuspid valve repair - Tricuspid valve regurgitation - Tricuspid valve - Leaflet approximation devices ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A total of 150 patients will be randomly assigned with a 2:1 allocation to either interventional (n=100) or control group (n=50). ##### Masking Info **Masking:** NONE **Masking Description:** Randomized controlled trial with open-label extension **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 150 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) **Intervention Names:** - Device: TriClip TTVr system (Abbott Vascular) - Device: PASCAL TTVr system (Edwards Lifesciences) **Label:** Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients will continue the SOC with heart failure medication following the European Society of Cardiology guideline 2021 recommendations (e.g. diuretics) **Label:** Standard Of Care (SOC) **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) **Description:** Edge-to-edge leaflet approximation for the tricuspid valve **Name:** TriClip TTVr system (Abbott Vascular) **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Transcatheter Edge-to-Edge Repair (TEER) on top of the Standard Of Care (SOC) **Description:** Edge-to-edge leaflet approximation for the tricuspid valve **Name:** PASCAL TTVr system (Edwards Lifesciences) **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Quality of Life is measured with the Kansas City Cardiomyopathy Questionnaire with a 5 point change as clinically significant (0-100 points, higher score is better outcome) **Measure:** Hierarchical composite of all-cause mortality, heart failure hospitalization and Quality of Life **Time Frame:** 12 months #### Secondary Outcomes **Description:** Mortality of any cause **Measure:** All-cause mortality **Time Frame:** 12 months **Description:** Hospitalization for acute decompensated heart failure **Measure:** Hospitalization for heart failure **Time Frame:** 12 months **Description:** 5 point change is considered clinically significant (0-100 points with higher score is a better outcome), change of 5 points in Kansas City Cardiomyopathy Questionnaire is considered clinically meaningful **Measure:** Change in Kansas City Cardiomyopathy Questionnaire **Time Frame:** 12 months **Description:** Cardiovascular mortality, myocardial infarction, stroke, major bleeding, device embolisation, new onset renal failure, endocarditis requiring surgery, non-elective cardiovascular surgery for device related adverse events. **Measure:** Number of participants without Major Adverse Events (MAE) **Time Frame:** 30 days and 12 months **Description:** ranging from 0 to 4 (no limitation to severe limitation) **Measure:** Change in New York Heart Association **Time Frame:** 12 months **Description:** Distance in meters (higher score is a better outcome) **Measure:** Change in 6-Minute Walk Test **Time Frame:** 12 months **Description:** Echocardiographic assessment of Tricuspid Regurgitation (at least from severe to moderate or less) **Measure:** Reduction tricuspid regurgitation **Time Frame:** 30 days, 6 months and 12 months **Description:** The investigators will compare the cost-effectiveness of the intervention group versus the control group based on lifetime horizon by constructing a Markov model with model parameters populated from the trial results as well as other published literature. The model will estimate the incremental cost-effectiveness ratio between the two groups **Measure:** Cost-effectiveness as assessed by the Markov model **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. The patient is symptomatic (New York Heart Association Functional Class II, III or ambulatory class IV) despite Standard Of Care (SOC). The Central Screening Committee (CSC) will assess whether the patient is receiving SOC. The CSC will also ensure that in case of the presence of atrial fibrillation, left sided heart valve disease (not requiring intervention) or coronary artery disease, conditions are first treated adequately with medication and/or (surgical) intervention. 2. The patient suffers from ≥ grade 3 isolated TR as determined by the assessment of a qualifying transthoracic echocardiogram (TTE) and three-dimensional transesophageal echocardiogram (3DTEE) and confirmed by the CSC, according to European Association for Percutaneous Cardiovascular Interventions (Tricuspid Focus Group) consensus document (in press). Note: If cardiac procedure(s) occur after eligibility was determined, TR grade will be re-assessed 30 days after the procedure. 3. The cardiac surgeon of the sites' local heart team concurs that the patient is at high estimated risk for mortality or morbidity with TV surgery. 4. The patient is ≥18 years of age at time of consent. 5. The patient must provide written informed consent prior to any trial related procedure. Exclusion Criteria: 1. Systolic pulmonary artery pressure (sPAP) \> 70 mmHg or fixed pre-capillary pulmonary hypertension as assessed by right heart catheterization. Severe uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 180 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 110 mmHg. 2. Any condition that would interfere with a TTVr procedure, such as prior tricuspid valve repair or tricuspid valve leaflet anatomy which may preclude device implantation (e.g. calcification in grasping area, a severe coaptation defect of the tricuspid leaflets (no clip placement possible), pacemaker or Implantable Cardioverter Defibrillator (ICD) leads that would prevent appropriate placement or visualization of TTVr devices, Ebstein Anomaly (normal annulus position, but valve leaflets attached to walls and septum of the right ventricle), tricuspid valve anatomy non evaluable by echo, known allergy or hypersensitivity to dual antiplatelet therapy AND anticoagulant therapy or to device materials, femoral venous mass or thrombus or vegetation. 3. Indication for left-sided (e.g. severe aortic stenosis, severe mitral regurgitation) or pulmonary valve correction within prior 60 days. Note: concomitant mitral valve disease (e.g. mitral regurgitation) will be treated first and patients will be reassessed for the trial after 60 days. 4. Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg. 5. Left Ventricular Ejection Fraction (LVEF) ≤20% 6. Active endocarditis, active rheumatic heart disease, other ongoing infection requiring antibiotic therapy (enrolment possible 30 days after discontinuation of antibiotics with no active infection) or leaflets degenerated from rheumatic disease (i.e. noncompliant, perforated) 7. Myocardial infarction known unstable angina, or percutaneous coronary intervention within prior 30 days. 8. Hemodynamic instability defined as systemic systolic pressure \<90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support or hemodynamic support device (e.g. intra-aortic balloon pump). 9. Cerebrovascular Accident (CVA) within prior 90 days 10. Chronic dialysis 11. Bleeding disorders or hypercoagulable state, inability to use dual antithrombotic therapy due to contraindication, allergy or hypersensitivity 12. Active peptic ulcer or active gastrointestinal (GI) bleeding 13. Life expectancy of less than 12 months 14. Subject currently participating in another clinical trial (not yet completed primary endpoint) or in another clinical investigation for valvular heart disease. 15. Pregnant or nursing patients or those who plan pregnancy during the course of the trial. Women of childbearing age are required to have a negative pregnancy test 7 days prior to baseline visit. Women of childbearing age should be instructed to use safe contraception or have a sterilized regular partner. 16. Presence of anatomic or comorbid conditions, or other medical, social or psychological conditions that, in the eye of the investigator, limits the subject's ability to participate in the clinical investigation or comply with follow-up requirements, or impact the scientific soundness of the investigation results. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Amsterdam **Country:** Netherlands **Facility:** Amsterdam UMC **Location 2:** **City:** Groningen **Country:** Netherlands **Facility:** UMC Groningen **Location 3:** **City:** Leiden **Country:** Netherlands **Facility:** Leiden UMC **Location 4:** **City:** Maastricht **Country:** Netherlands **Facility:** Maastricht UMC+ **Location 5:** **City:** Nieuwegein **Country:** Netherlands **Facility:** St. Antonius Hospital Nieuwegein **Location 6:** **City:** Rotterdam **Country:** Netherlands **Facility:** Erasmus University Medical Center #### Overall Officials **Official 1:** **Affiliation:** St. Antonius Hospital **Name:** M.J. Swaans, MD,PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** These criteria will be made in consultation with the legal advisor of our institution and have not yet been drafted. Specific degrees in the field of research have to be demonstrated, as wel as links with hospitals or research institutes of the researcher/physician (e.g. an employee contract) **Description:** At the end of the study, the data will be locally saved at the st. Antonius Hospital and can be made available at request for reuse in other studies. **Info Types:** - STUDY_PROTOCOL - SAP **IPD Sharing:** YES **Time Frame:** After publishing the main study articles, raw and modified data can be made available at request ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006349 - Term: Heart Valve Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure, Right-Sided - ID: M17014 - Name: Tricuspid Valve Insufficiency - Relevance: HIGH - As Found: Tricuspid Valve Regurgitation - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M9437 - Name: Heart Valve Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure - ID: D000014262 - Term: Tricuspid Valve Insufficiency ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M7411 - Name: Diuretics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06061679 **Acronym:** OMRON **Brief Title:** Impact of Switching COPD Patients From Inhaler Devices to the Omron C28P Nebuliser. **Official Title:** Impact of Switching COPD Patients From Inhaler Devices to the Omron C28P Nebuliser: a Prospective, Real-world Study #### Organization Study ID Info **ID:** 5432 #### Organization **Class:** OTHER **Full Name:** Fondazione Policlinico Universitario Agostino Gemelli IRCCS ### Status Module #### Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-29 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-25 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-04 **Type:** ESTIMATED #### Start Date **Date:** 2023-11 **Type:** ESTIMATED **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2023-09-29 **Type:** ACTUAL **Study First Submit Date:** 2023-09-01 **Study First Submit QC Date:** 2023-09-25 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** University of Florence, UNIFI University of Florence, Florence, Italy Florence #### Lead Sponsor **Class:** OTHER **Name:** Fondazione Policlinico Universitario Agostino Gemelli IRCCS #### Responsible Party **Investigator Affiliation:** Fondazione Policlinico Universitario Agostino Gemelli IRCCS **Investigator Full Name:** BONINI MATTEO **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The cornerstone of COPD therapy is based on the use of inhalation drugs. The correct use of devices is crucial; a suboptimal use technique is the cause of a possible clinical deterioration with a consequent increase in exacerbations and healthcare expenditure. Inhalation of drugs by nebulizer, in specific populations of patients who have shown poor adherence to inhalation therapy and poor symptomatological control, could be a more advantageous therapeutic strategy than pMDIs or DPIs, not requiring coordination at the time of delivery and not requiring an effective inspiratory effort. The objective of this study is to evaluate the effects of the transition from portable inhalers (pMDIs or DPIs) to an innovative prototype Omron C28P nebulizer, measured primarily as changes in treatment adhesion and respiratory symptoms. The sudy design is open, single-arm, real-life, prospective study conducted in two tertiary level respiratory centers in Italy, with assessments conducted on the occasion of patients' visits to their doctor. **Detailed Description:** The cornerstone of pharmacological treatment of COPD is represented by bronchodilator and corticosteroid medications delivered by pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Any inhaler device category can be equally effective in treating patients if properly used. However, each device exhibits distinct properties that warrant consideration in achieving successful medication delivery. Errors frequently observed in patients with obstructive pulmonary diseases are incorrect coordination between inspiration and pMDIs activation and insufficient inspiratory effort or wrong device preparation with DPIs. Suboptimal inhaler technique is the prominent reason for the lack of efficacy and can contribute to poor adherence to medications that, in turn, is associated with worsening in disease control, increased rate of exacerbations, increased healthcare resource consumption, and consequently increased healthcare expenditure. Inhaler devices, which may seem simple to use to healthcare providers, frequently present challenges particularly for elderly patients with COPD. The combined effects of co-morbidities, the complexity of the accompanying medication regimens, as well as age- and disease-related lung function decline may add to the complexity of using different inhalers. Once set up, nebulisers are easier for patients to use than pMDIs or DPIs as they only require tidal respiration for effective drug delivery with, therefore, no need to coordinate inspiration with device activation as for pMDIs, or to require high inspiratory effort as for DPIs. The primary aim of the present study is to assess the effect on inhaler adherence and disease control of switching patients from their portable inhalers (either pMDIs or DPIs) to the Omron C28P nebuliser, as assessed by means of the Test of Adherence to Inhalers (TAI) questionnaire and the COPD Assessment Test (CAT), respectively. The investigators plan to enroll 99 adult outpatients of both genders with a diagnosis of COPD of any functional severity; a sample size of 99 patients was chosen to design the study to have a 80% statistical power of detecting a difference of 2.07 (±1.03 SD) and of 3 (±5 SD) in TAI and CAT score, respectively, after device switching. The study consists of a baseline (T0) and 2 follow-up visits at 8 (T1) and 24 (T2) weeks (±2) after enrolment. On each study visit, after completion of clinical history and measurements of vital parameters, patients will be requested to rate their adherence to inhalers by filling the TAI questionnaire. Impact of COPD on health status and dyspnoea perception will be assessed by measuring the CAT score and the mMRC score. After completion of the above-mentioned procedures, patients will be carefully instructed by trained investigators on the use of the Omron C28P nebuliser. To this end, practical session with the nebuliser and dedicated videos will be used. ### Conditions Module **Conditions:** - COPD (Chronic Obstructive Pulmonary Disease) With Acute Lower Respiratory Infection ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Open, single-arm, real-life, prospective study ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 99 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients diagnosed with COPD using the study device (OMRONC28P) for 24 weeks. **Intervention Names:** - Device: Omron C28P nebuliser **Label:** Omron C28P cohort **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Omron C28P cohort **Description:** switch from portable inhalers to the Omron C28P nebuliser **Name:** Omron C28P nebuliser **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The primary aim of the present study is to assess the effect on inhaler adherence to the Omron C28P, assessed by means of the Test of Adherence to Inhalers (TAI) questionnaire **Measure:** The primary aim of the present study is to assess the effect on inhaler adherence to the Omron C28P **Time Frame:** 24 weeks **Description:** The co-primary aim of the present study is to assess the effect on disease control of switching patients from their portable inhalers (either pMDIs or DPIs) to the Omron C28P assessed by means of the COPD Assessment Test (CAT) **Measure:** The co-primary aim of the present study is to assess the effect on disease control of switching patients from their portable inhalers (either pMDIs or DPIs) to the Omron C28P **Time Frame:** 24 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * COPD patients treated by inhaled bronchodilators, corticosteroids or their combinations delivered by inhaler devices * COPD patients not adherent (TAI ≤ 45) to recommended therapy * COPD patients with a CAT score ≥18. * Must be capable of giving informed consent to participate, and available to comply with the requirements and procedures foreseen by the study protocol. Exclusion Criteria: * COPD patients with history of recent (\< 4 weeks) upper respiratory tract infections and/or airways exacerbations * patients with recent (\< 2 months) pulmonary surgery or any active diseases that, in the judgement of the investigator, may interfere with the study protocol. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** matteo.bonini@policlinicogemelli.it **Name:** Matteo Bonini, Professor **Phone:** 0630157724 **Role:** CONTACT **Contact 2:** **Email:** stefania.cortese@guest.policlinicogemelli.it **Name:** Stefania Cortese, Dr **Phone:** 0630157724 **Role:** CONTACT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000007239 - Term: Infections ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: HIGH - As Found: Respiratory Infection - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: HIGH - As Found: Obstructive Pulmonary Disease - ID: M23449 - Name: Pulmonary Disease, Chronic Obstructive - Relevance: HIGH - As Found: Chronic Obstructive Pulmonary Disease - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000029424 - Term: Pulmonary Disease, Chronic Obstructive ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04590079 **Acronym:** Epikarthrose **Brief Title:** Innovative Device for Pain Management by Millimeter Band Radiation : Electronic-Pain Killer. **Official Title:** Innovative Device for Pain Management by Millimeter Band Radiation : Electronic-Pain Killer. Evaluation in Patients With Peripheral Osteoarthritis: A Single Center, Prospective, Randomized in Cross-over, Comparative and Open-label Study #### Organization Study ID Info **ID:** 38RC20.088 #### Organization **Class:** OTHER **Full Name:** University Hospital, Grenoble ### Status Module #### Completion Date **Date:** 2022-08-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-02-14 **Type:** ACTUAL **Last Update Submit Date:** 2023-02-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-08-24 **Type:** ACTUAL #### Start Date **Date:** 2020-12-14 **Type:** ACTUAL **Status Verified Date:** 2022-02 #### Study First Post Date **Date:** 2020-10-19 **Type:** ACTUAL **Study First Submit Date:** 2020-09-18 **Study First Submit QC Date:** 2020-10-09 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Remedee SA **Class:** NETWORK **Name:** Clinical Investigation Centre for Innovative Technology Network #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Grenoble #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** In this study, in addition of conventional treatment, the efficacy of the medical device, Remedee One, in medical care of patients with peripheral osteoarthritis pain is evaluated. **Detailed Description:** Osteoarthritis affects 10 millions people in France (17% of the population). It's the second cause of disability and consultation after the cardiovascular diseases in France. For the moment, there is no curative treatment for osteoarthritis The main clinical sign of this disease is pain and care is based on the treatment of pain and on the improvement of functionnal disability. The proposed treatments are mainly based on the use of oral analgesics treatments . At present, patients report to be insufficiently relieved. New strategies need to be developed. The hypothesis is that the use of an innovative medical device, Remedee One, can reduce the pain felt by patients, improve their quality of life and reduce the analgesics consumption. The choice is oriented on the peripheral osteoarthritis and excludes spinal osteoarthritis because it's an osteoarthritis always asymptomatic and painless. ### Conditions Module **Conditions:** - Osteoarthritis - Peripheral - Pain **Keywords:** - Osteoarthritis - Pain - Medical device - Radiation in millimeter band - Life quality - Peripheral - Treatment ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** First intervention group: patients with peripheral osteoarthritis who will have: 3 months of conventional pain treatment and daily sessions with the medical device followed by 1 month of wash out and then 3 months of conventional pain treatment. Second intervention group: patients with peripheral osteoarthritis who will have: 3 months of conventional pain treatment followed by 1 month of wash out followed by 3 months of conventional pain treatment and daily sessions with the medical device. ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients suffering from peripheral osteoarthritis who will have : 3 months of conventional pain treatment and daily sessions with the medical device - 1 month of wash-out - 3 months of conventional pain treatment. **Intervention Names:** - Device: Conventional pain treatment with daily sessions with innovative medical device, Remedee One, for pain management by Millimeter Band Radiation **Label:** First intervention group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients suffering from peripheral osteoarthritis who will have : 3 months of conventional pain treatment - 1 month of wash-out - 3 months of conventional pain treatment and daily sessions with the medical device. **Intervention Names:** - Device: Conventional pain treatment with daily sessions with innovative medical device, Remedee One, for pain management by Millimeter Band Radiation **Label:** Second intervention group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - First intervention group - Second intervention group **Description:** Conventional pain treatement with daily sessions with innovative medical device for pain management (radiation in millimeter band) at the rate of 1 to 3 sessions by day of 40 minutes for 3 months. **Name:** Conventional pain treatment with daily sessions with innovative medical device, Remedee One, for pain management by Millimeter Band Radiation **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** At the end of each month for each period of the cross-over, the pain is evaluated using a visual analogue scale (VAS). **Measure:** Comparison of pain (evaluates with visual analogue scale ) with and without the use of medical device in patients with peripheral osteoarthritis who benefit from their conventional pain treatment. **Time Frame:** 7 months #### Secondary Outcomes **Description:** At the end of each of the cross-over period, the quality of life is evaluated with the score obtained using the EQ5D-5L (5-level EuroQol version) questionnaire. **Measure:** Comparison of quality of life (evaluated with the EQ5D5L questionnaire), with and without the use of the medical device, in patients with peripheral osteoarthritis who benefit from their conventional pain treatment. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the depressive state and coping are evaluated with the score obtained using the HAD (Hospital Anxiety and Depression Scale) questionnaire. **Measure:** Comparison of depressive state and coping (evaluated with the HAD questionnaire), with and without the use of the medical device in patients with peripheral osteoarthritis receiving their conventional pain treatment.. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the functional capacity is evaluated with the score obtained using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) questionnaire. **Measure:** Comparison of functional capacity (evaluated with the WOMAC questionnaire) with and without the use of the medical device in patients suffering from osteoarthritis of the lower limbs and benefiting from their conventional pain treatment. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the functional capacity is evaluated with the score obtained using the DREISER (Functional Index for Hand OsteoArthritis) questionnaire. **Measure:** Comparison of the functional capacity (evaluatet with the DREISER questionnaire) with and without the use of the medical device in patients with digital osteoarthritis and benefiting from their conventional pain treatment. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the analgesic consumption are assessed by their class, dose and number of dose taken. **Measure:** Number of analgesic consumption, with and without the use of the medical device, in patients with peripheral osteoarthritis and benefiting from their conventional pain treatment. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the number of drugs consumed (phytotherapy, homeopathy, food supplements), the number of medical acts, medical consultations, hospitalisations, the number of complementary medicine (acupuncture...) and psycho-behavioural therapies are assessed. **Measure:** Number of care consumption with and without the use of the medical device in patients with peripheral osteoarthritis and benefiting from their conventional pain treatment. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the number of adverse effects from the medical device is assessed. **Measure:** Adverse effect from the medical device. **Time Frame:** 7 months **Description:** At the end of each of the cross-over period, the sleep quality is evaluated using a qualitative visual satisfaction scale (score between 0 to 10). **Measure:** Charaterization of the sleep quality (evaluated with a qualitative visual satisfaction scale) with and without the use of medical device in patients with peripheral osteoarthritis and benefiting from their conventional pain treatment. **Time Frame:** 7 months **Description:** Log files of the medical device are extracted. The number and the duration of each session are analysed. **Measure:** Description of the medical device use **Time Frame:** 7 months **Description:** Open question will be asked in a questionnaire without scale. A descriptive analysis will be done with the answers. **Measure:** Medical device acceptability : descriptive analysis **Time Frame:** 7 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult ≥ 50 years * Patient followed in rhumatology consultation or at the center of the pain of the University Hospital of Grenoble or in liberal for peripheral osteoarthritis (ankle, knee, hip, shoulder, elbow, digital) clinically and radiologically confirmed according to the recommendations of the American College of Rheumatology. * Patient with a pain score on a Visual Analog Scale (VAS) ≥ 4 on a numerical scale of 0 to 10 (average VAS intensity over the week prior to the inclusion visit), * Patient with a stable analgesic treatment without introduction of a new therapeutic class within the last 3 months, * Patient with a wrist size compatible with the size of the medical device * Patient affiliated to social security or beneficiary of such a scheme. * Having signed a consent to participate. Exclusion Criteria: * Patient with chronic inflammatory joint disease (chronic inflammatory rheumatism, rheumatoid arthritis, psoriatic rheumatism, spondyloarthritis, lupus), * Patient who received an intra-articular corticosteroid injection within 3 months prior to inclusion, * Patient with surgery scheduled within the next eight months, * Patient presenting at both wrists a dermatological pathology such as oozing dermatosis, hyper sweating or an unhealed lesion, * Patient having a piercing or implanted metallic material on both wrists, * Patient with a tattoo on both wrists, * Patient deprived of liberty by judicial or administrative decision * Patient subject to legal protection or unable to express his consent (guardianship or curatorship) * Patient in exclusion period of another interventional study **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Grenoble **Country:** France **Facility:** University Hospital **Zip:** 38043 #### Overall Officials **Official 1:** **Affiliation:** University Hospital, Grenoble **Name:** Caroline MAINDET, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Usichenko TI, Edinger H, Gizhko VV, Lehmann C, Wendt M, Feyerherd F. Low-intensity electromagnetic millimeter waves for pain therapy. Evid Based Complement Alternat Med. 2006 Jun;3(2):201-7. doi: 10.1093/ecam/nel012. Epub 2006 Apr 24. **PMID:** 16786049 #### See Also Links **Label:** Bourgeois P, Berenhaum F, Gibert E. Peut-on prévenir l'arthrose ? Arthrolink. **URL:** https://www.arthrolink.com/fr/dossiers-arthrose/tous-les-dossiers/peut-on-prevenir-l-arthrose **Label:** Innovative Device for Pain Management by Millimeter Band Radiation: Electronic-Pain Killer (EPIKARD) **URL:** https://clinicaltrials.gov/ct2/show/NCT03889288?term=EPIKARD&draw=2&rank=1 **Label:** Clinical Investigation Centre for Innovative Technology Network website **URL:** http://www.cic-it.fr/cic-it-grenoble.php ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis ### Intervention Browse Module - Browse Branches - Abbrev: Analg - Name: Analgesics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03524079 **Acronym:** RV-BrS **Brief Title:** Right Ventricle Morphology and Hemodynamics in BrS **Official Title:** Morphological and Functional Characteristics of the Right Ventricle in Patients With Brugada Syndrome #### Organization Study ID Info **ID:** RV & BrS #### Organization **Class:** OTHER **Full Name:** IRCCS Policlinico S. Donato ### Status Module #### Completion Date **Date:** 2019-11-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-05-18 **Type:** ACTUAL **Last Update Submit Date:** 2021-05-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-11-08 **Type:** ACTUAL #### Start Date **Date:** 2018-04-19 **Type:** ACTUAL **Status Verified Date:** 2021-05 #### Study First Post Date **Date:** 2018-05-14 **Type:** ACTUAL **Study First Submit Date:** 2018-04-19 **Study First Submit QC Date:** 2018-05-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** IRCCS Policlinico S. Donato #### Responsible Party **Investigator Affiliation:** IRCCS Policlinico S. Donato **Investigator Full Name:** Carlo Pappone **Investigator Title:** Head of Arrhythmology Department **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The study purpose is to evaluate the morphological, functional and electrophysiological characteristics of the right ventricle before and after ajmaline in patients diagnosed with Brugada syndrome as well as to correlate CMR findings and substrate size. **Detailed Description:** All consecutive patients with either spontaneous or ajmaline-induced BrS-ECG pattern will be screened. A total of 30 BrS patients and 30 normal age, sex and BSA matched normal controls will be selected and enrolled. Patients will perform cardiac magnetic resonance imaging to evaluate and compare morphological and functional characteristics of the 2 groups before and after ajmaline. BrS patients will also perform a standardized programmed ventricular stimulation protocol and electroanatomical mapping to determine the substrate size. ### Conditions Module **Conditions:** - Brugada Syndrome ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ajmaline 17-(Chloroacetate) Monohydrochloride **Intervention Names:** - Drug: Ajmaline 17-(Chloroacetate) Monohydrochloride **Label:** BrS Group #### Arm Group 2 **Description:** Ajmaline 17-(Chloroacetate) Monohydrochloride **Intervention Names:** - Drug: Ajmaline 17-(Chloroacetate) Monohydrochloride **Label:** No BrS group ### Interventions #### Intervention 1 **Arm Group Labels:** - BrS Group - No BrS group **Description:** Ajmaline 17-(Chloroacetate) Monohydrochloride(1mg/kg in 5 minutes) **Name:** Ajmaline 17-(Chloroacetate) Monohydrochloride **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Changes of PR, QRS, and QT parameters, before and after ajmaline in Brugada patients as compared with control subjects **Measure:** Electrocardiographic changes **Time Frame:** 1 day during Electrocardiography **Description:** MRI changes of left and right ventricular function before and after ajmaline in Brugada patients as compared with control subjects **Measure:** MRI changes of left and right ventricular function **Time Frame:** 1day during MRI **Description:** Changes of right ventricular areal strain before and after ajmaline in Brugada patients as compared with controls **Measure:** CMR parameters changes of the right and left ventricle function **Time Frame:** 1 day during CMR **Description:** electroanatomical epicardial mapping for substrate determination before and after ajmaline **Measure:** Electrical substrate changes of the right ventricle **Time Frame:** 1 day after ICD implantation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Brugada syndrome with either spontaneous or ajmaline- induced type 1 ECG pattern * Indication to ajmaline testing and programmed ventricular stimulation * Age \> or equal to 18 years * Written informed consent Exclusion Criteria: * Pregnancy * Contraindication to CMRI or to ajmaline * Live espectance \< 12 months **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** A total of 60 selected subjects (30 BrS patients and 30 normal controls) will be enrolled. ### Contacts Locations Module #### Locations **Location 1:** **City:** San Donato Milanese **Country:** Italy **Facility:** IRCCS Policlinico S. Donato **State:** Milano **Zip:** 20097 #### Overall Officials **Official 1:** **Affiliation:** IRCCS San Donato University Hospital Policlinico San Donato, Milan, Italy **Name:** Carlo Pappone, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Pappone C, Santinelli V, Mecarocci V, Tondi L, Ciconte G, Manguso F, Sturla F, Vicedomini G, Micaglio E, Anastasia L, Pica S, Camporeale A, Lombardi M. Brugada Syndrome: New Insights From Cardiac Magnetic Resonance and Electroanatomical Imaging. Circ Arrhythm Electrophysiol. 2021 Nov;14(11):e010004. doi: 10.1161/CIRCEP.121.010004. Epub 2021 Oct 25. **PMID:** 34693720 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000075224 - Term: Cardiac Conduction System Disease - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M27508 - Name: Brugada Syndrome - Relevance: HIGH - As Found: Brugada Syndrome - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M1472 - Name: Cardiac Conduction System Disease - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: T882 - Name: Brugada Syndrome - Relevance: HIGH - As Found: Brugada Syndrome ### Condition Browse Module - Meshes - ID: D000053840 - Term: Brugada Syndrome - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Ancestors - ID: D000000889 - Term: Anti-Arrhythmia Agents - ID: D000061567 - Term: Voltage-Gated Sodium Channel Blockers - ID: D000026941 - Term: Sodium Channel Blockers - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: ChanBlk - Name: Channel Blockers - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M3752 - Name: Ajmaline - Relevance: HIGH - As Found: Myxoid - ID: M4213 - Name: Anti-Arrhythmia Agents - Relevance: LOW - As Found: Unknown - ID: M23177 - Name: Sodium Channel Blockers - Relevance: LOW - As Found: Unknown - ID: M30025 - Name: Diuretics, Potassium Sparing - Relevance: LOW - As Found: Unknown - ID: T357 - Name: Ajmaline - Relevance: HIGH - As Found: Myxoid ### Intervention Browse Module - Meshes - ID: D000000404 - Term: Ajmaline ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05965479 **Acronym:** DECIPHER **Brief Title:** Developing ctDNA Guided Adjuvant Therapy for Gastrooesophageal Cancer **Official Title:** A Single Arm Phase II Trial of Trastuzumab Deruxtecan in Patients With Gastrooesophageal Adenocarcinoma Cancer Who Are ctDNA and HER2 Positive #### Organization Study ID Info **ID:** 68838 #### Organization **Class:** OTHER **Full Name:** University of Southampton #### Secondary ID Infos **ID:** 2022-003445-34 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2028-04-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-16 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-14 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-03-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-04-10 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2023-07-28 **Type:** ACTUAL **Study First Submit Date:** 2023-07-06 **Study First Submit QC Date:** 2023-07-27 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** AstraZeneca **Class:** INDUSTRY **Name:** Natera, Inc. #### Lead Sponsor **Class:** OTHER **Name:** University of Southampton #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Multicentre, single arm, open label UK phase II trial to assess the efficacy of trastuzumab deruxtecan in reducing micrometastatic disease burden in HER2 positive GOA patients who are ctDNA positive after chemotherapy and surgery. 25 patients will be recruited from approximately 15 NHS secondary care sites. **Detailed Description:** Gastrooesophageal (GOA) cancer is a common, global cancer which often presents at an advanced stage. Those diagnosed early will generally have neoadjuvant treatment with FLOT chemotherapy followed by surgery followed by the same FLOT chemotherapy post surgery. Treatment however is curative in less than 50%. Circulating tumour DNA (ctDNA) is found in the bloodstream. It refers to DNA that comes from cancerous cells and tumours. If ctDNA is positive it means that there are microscopic traces of tumour in the bloodstream (minimal residual disease). Patients who are ctDNA positive after chemotherapy and surgery are less likely to benefit from further FLOT chemotherapy and more likely to relapse. HER2 positive describes cells that have a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that make too much HER2 may grow more quickly and are more likely to spread to other parts of the body. Trastuzumab deruxtecan (T-DXd) is an antibody that targets HER2 cells. It attaches to the HER2 cells on the tumour and destroys them. In the UK, trastuzumab deruxtecan (Enhertu) is currently offered to patients with advanced breast cancer who are HER2 positive. In the US, Israel and Japan it is licenced in patients with advanced HER2 positive GOA. DECIPHER aims to treat patient's with GOA post-surgery who are both HER2 and ctDNA positive with trastuzumab deruxtecan (Enhertu) instead of standard care FLOT chemotherapy. The aim of the trial is to treat the minimal residual disease reducing the chance of relapse. All trial patients will be followed for up to 2 years to record their response to treatment. 25 patients will be recruited over 18 months. Patients will be treated with 6.4 mg/kg trastuzumab deruxtecan every 21 days for 8 cycles. ### Conditions Module **Conditions:** - Gastrooesophageal Cancer **Keywords:** - Gastrooesophageal adenocarcinoma - Oesophageal cancer - Gastric cancer - HER2 - ctDNA - Minimal residual disease ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants in the study will be treated with trastuzumab deruxtecan at a dose of 6.4 mg/kg intravenously every 21 days for 8 cycles. If required, patients may dose reduce to level -1 or level -2: * Dose level 0 is 6.4 mg/kg intravenously every 21 days * Dose level -1 is 5.4 mg/kg intravenously every 21 days * Dose level -2 is 4.4 mg/kg intravenously every 21 days T-DXd will be administered using an IV bag containing 5% (w/v) Dextrose Injection infusion solution and delivered through an IV administration set with a 0.2 or 0.22 μm filter. The standard infusion time for T-DXd is approximately 90 minutes +/- 10 minutes for the first infusion. If the first infusion is well tolerated and the participant does not experience an infusion-related reaction, then the minimum infusion time for subsequent cycles is 30 minutes. However, if there are interruptions during the infusion, the total time must not exceed 3 hours at room temperature. **Intervention Names:** - Drug: Trastuzumab deruxtecan **Label:** Trastuzumab deruxtecan **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Trastuzumab deruxtecan **Description:** Trastuzumab deruxtecan is an antibody-drug conjugate that contains trastuzumab covalently linked to deruxtecan, a topoisomerase I inhibitor. It is given by intravenous infusion. **Name:** Trastuzumab deruxtecan **Other Names:** - Enhertu **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Absolute and relative ctDNA reduction in individual patients, duration of ctDNA response, correlation between ctDNA response and radiological recurrence and survival outcomes **Measure:** Measurement of the quantity of ctDNA present in blood using the Signatera assay **Time Frame:** From date of surgery until the date of recurrence or date of death from any cause, whichever comes first, assessed up to 30 months **Description:** Correlation between tumour HER2 IHC and copy numbers status, other molecular markers and ctDNA dynamics and patient outcomes **Measure:** Measurement of the quantity of ctDNA present in blood using Signatera assay **Time Frame:** From date of surgery until the date of recurrence or date of death from any cause, whichever comes first, assessed up to 30 months #### Primary Outcomes **Description:** Percentage of people who are classed ctDNA negative, as measured by the Signatera assay **Measure:** ctDNA clearance **Time Frame:** At the end of Cycle 4 (each cycle is 21 days) #### Secondary Outcomes **Description:** Percentage of people who are ctDNA negative after each cycle **Measure:** ctDNA clearance (yes/no) **Time Frame:** Up to completion of cycle 8 (where each cycle is 21 days) **Description:** Time from surgery to recurrence of macroscopic disease of radiological imaging or death **Measure:** Disease Free Survival **Time Frame:** At 12 months and 24 months **Description:** Time from surgery to death **Measure:** Overall survival **Time Frame:** 12, 18 and 24 months **Description:** Quality of life scored from QLQ-C30 **Measure:** QLQ-C30 **Time Frame:** Up to 30 months post surgery **Description:** Quality of life scored from QLQ-OG25 **Measure:** QLQ-OG25 **Time Frame:** Up to 30 months post surgery **Description:** Quality of life scored from EQ-5D-5L **Measure:** EQ-5D-5L **Time Frame:** Up to 30 months post surgery **Description:** Frequency of adverse events and percentage of people experiencing them **Measure:** Safety and tolerability of T-DXd **Time Frame:** Up to 100 days post last dose of trial treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pathologically documented adenocarcinoma of the stomach (clinical stage before surgery of AJCC I-III), gastroesophageal junction, or lower oesophagus (to include Type I Siewert only), with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results. * ctDNA positive after surgery as per Signatera assay * Capable of giving signed informed consent prior to any mandatory study specific procedures, sampling, or analyses and which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. * Male and female participants must be at least 18 years of age at the time of signing the ICF. * Treated with neoadjuvant chemotherapy before surgery for at least six weeks. * Surgical resection with clear margins (R0). * Recovered from surgery in the opinion of the investigator. * No previous treatment with trastuzumab or other HER2 directed therapy. * No evidence of metastatic disease on post-surgical CT. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Has LVEF ≥ 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before treatment. * Has adequate organ and bone marrow function within 14 days before treatment allocation as below: * Platelet count ≥ 100x109/L (Platelet transfusion is not allowed within 1 week prior to screening assessment, use of thrombopoietin receptor agonists is not allowed within 2 weeks prior to screening assessment) * Haemoglobin ≥ 80 g/L. Participants requiring transfusions or growth factor support to maintain haemoglobin ≥ 80 g/L are not eligible. (Red blood cell transfusions is not allowed within 1 week prior to screening assessment) * Absolute neutrophil count ≥ 1.5 x 109/L (granulocyte-colony stimulating factor \[G-CSF\] administration is not allowed within 1 week prior to screening assessment * ALT/AST ≤ 3 x ULN * Total bilirubin ≤ 1.5 x ULN or \< 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) * Serum albumin ≥ 3.0 g/dl * Creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault equation * Adequate clotting function International Normalized Ratio (INR) or prothrombin time and either partial thromboplastin or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. * Reproduction: * Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilised male partner. * For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IMP. * Women of childbearing potential are defined as those who are not surgically sterile (i.e., underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. I. Women aged \<50 years will be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the site. II. Women aged ≥ 50 years will be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago. * Female participants of childbearing potential who are sexually active with a non-sterilised male partner must use at least one highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 7 months after the last dose of IMP. Not all methods of contraception are highly effective. * Female participants must refrain from breastfeeding and must not donate (or retrieve their own for use) ova, from the time of screening, throughout the study treatment period, and for at least 7 months after the last dose of IMP. * Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasion abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. * Non-sterilised male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IMP. * It is strongly recommended for the female partners of a male participant to also use at least one highly effective method of contraception throughout this period. In addition, male participants should refrain from fathering a child or freezing or donating sperm from screening, throughout the study treatment period, and for at least 4 months after the last dose of IMP. * Investigators should advise male participants on the conservation of sperm prior to starting treatment because of the possibility of irreversible infertility/testicular damage due to IMP administered in this study. * Female subjects must not donate, or retrieve for their own use, ova from the time of enrolment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova prior to enrolment in this study, can be discussed with the patient if clinically appropriate to do so. Exclusion Criteria: * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AE's, or compromise the ability of the participant to give written informed consent. * Participants with a medical history of myocardial infarction within 6 months before treatment or symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\<6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer)m and without myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out myocardial infarction. * Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG * History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Any of the following: 1. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., clinically significant pulmonary emboli within 3 months of treatment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, clinically significant pleural effusion etc.) 2. Any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), where there is documented, or a suspicion of, pulmonary involvement at the time of screening 3. Prior pneumonectomy (complete) * Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals * Multiple primary malignancies within the prior 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumours curatively treated. * A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt. * Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline. The following exemption will apply; stable chronic G2 toxicity which in the opinion of the investigator is not reasonably expected to be exacerbated by treatment with study drugs. * Known allergy or hypersensitivity to T-DXd or any of the study drug components * History of severe hypersensitivity reactions or other monoclonal antibodies * Pregnant or breastfeeding female participants, or participants who are planning to become pregnant * Involvement in the planning and/or conduct of the study * Has substance abuse or any other medical conditions, that may, in the opinion of the investigator, interfere with the subjects participation in the clinical study or evaluation of the clinical study results * Receipt of live, attenuated vaccine within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP * Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Judgement by the Investigator that the participant should not participate in the study, if the participant is unlikely to comply with study procedures, restrictions, and requirements. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** elizabeth.smyth2@nhs.net **Name:** Elizabeth Smyth **Phone:** 023 81205773 **Role:** CONTACT **Contact 2:** **Email:** decipher@soton.ac.uk **Name:** Daniel Griffiths **Phone:** 02381205154 **Role:** CONTACT #### Locations **Location 1:** **City:** Southampton **Contacts:** ***Contact 1:*** - **Name:** Andrew Bateman - **Role:** CONTACT ***Contact 2:*** - **Name:** Andrew Bateman - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** University Hospital Southampton NHS Foundation Trust, Southampton General Hospital **State:** Hampshire **Status:** NOT_YET_RECRUITING **Zip:** SO16 6YD **Location 2:** **City:** Guildford **Contacts:** ***Contact 1:*** - **Name:** Madeleine Hewish - **Role:** CONTACT ***Contact 2:*** - **Name:** Madeleine Hewish - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Royal Surrey NHS Foundation Trust, Royal Surrey County Hospital **State:** Surrey **Status:** NOT_YET_RECRUITING **Zip:** GU2 7XX **Location 3:** **City:** Coventry **Contacts:** ***Contact 1:*** - **Name:** Hannah Tween - **Role:** CONTACT ***Contact 2:*** - **Name:** Hannah Tween - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** University Hospitals Coventry and Warwickshire, University Hospital Coventry **State:** Warwickshire **Status:** RECRUITING **Zip:** CV2 2DX **Location 4:** **City:** Belfast **Contacts:** ***Contact 1:*** - **Name:** Richard Turkington - **Role:** CONTACT ***Contact 2:*** - **Name:** Richard Turkington - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Belfast Health and Social Care Trust, Belfast City Hospital **Status:** NOT_YET_RECRUITING **Zip:** BT9 7AB **Location 5:** **City:** Cambridge **Contacts:** ***Contact 1:*** - **Name:** Hugo Ford - **Role:** CONTACT ***Contact 2:*** - **Name:** Hugo Ford - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Cambridge University Hospital NHS Foundation Trust, Addenbrookes Hospital **Status:** RECRUITING **Zip:** CB2 0QQ **Location 6:** **City:** Derby **Contacts:** ***Contact 1:*** - **Name:** Lalith Seneviratne - **Role:** CONTACT ***Contact 2:*** - **Name:** Lalith Seneviratne - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** University Hospitals of Derby and Burton NHS Foundation Trust, Royal Derby Hospital **Status:** NOT_YET_RECRUITING **Zip:** DE22 3NE **Location 7:** **City:** Dundee **Contacts:** ***Contact 1:*** - **Name:** Russell Petty - **Role:** CONTACT ***Contact 2:*** - **Name:** Russell Petty - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** NHS Tayside, Ninewells Hospital **Status:** RECRUITING **Zip:** DD2 1UB **Location 8:** **City:** Hull **Contacts:** ***Contact 1:*** - **Name:** Rajarshi Roy - **Role:** CONTACT ***Contact 2:*** - **Name:** Rajarshi Roy - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Hull University Teaching Hospitals NHS Trust, Castel Hill Hospital **Status:** RECRUITING **Zip:** HU16 5JQ **Location 9:** **City:** Leeds **Contacts:** ***Contact 1:*** - **Name:** Daniel Swinson - **Role:** CONTACT ***Contact 2:*** - **Name:** Daniel Swinson - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Leeds Teaching Hospitals NHS Trust, St James's University Hospital **Status:** RECRUITING **Zip:** LS9 7TF **Location 10:** **City:** London **Contacts:** ***Contact 1:*** - **Name:** John Bridgewater - **Role:** CONTACT ***Contact 2:*** - **Name:** John Bridgewater - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** University College London Hospitals NHS Foundation Trust, University College Hospital London **Status:** NOT_YET_RECRUITING **Zip:** NW1 2BU **Location 11:** **City:** London **Contacts:** ***Contact 1:*** - **Name:** Sarah Ngan - **Role:** CONTACT ***Contact 2:*** - **Name:** Sarah Ngan - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Guys & St Thomas NHS Foundation Trust, Guy's Hospital **Status:** NOT_YET_RECRUITING **Zip:** SE1 9RT **Location 12:** **City:** Manchester **Contacts:** ***Contact 1:*** - **Name:** Was Mansoor - **Role:** CONTACT ***Contact 2:*** - **Name:** Was Mansoor - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** The Christie NHS Foundation Trust **Status:** RECRUITING **Zip:** M20 4BX **Location 13:** **City:** Norwich **Contacts:** ***Contact 1:*** - **Name:** Daniel Holyoake - **Role:** CONTACT ***Contact 2:*** - **Name:** Daniel Holyoake - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Norfolk and Norwich University Hospitals NHS Foundation Trust, Norfolk and Norwich University Hospital **Status:** NOT_YET_RECRUITING **Zip:** NR4 7UY **Location 14:** **City:** Oxford **Contacts:** ***Contact 1:*** - **Name:** Elizabeth Smyth - **Role:** CONTACT ***Contact 2:*** - **Name:** Elizabeth Smyth - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Oxford University Hospitals NHS Trust, Churchill Hospital **Status:** RECRUITING **Zip:** OX3 7LE **Location 15:** **City:** Preston **Contacts:** ***Contact 1:*** - **Name:** Catherine Mitchell - **Role:** CONTACT ***Contact 2:*** - **Name:** Catherine Mitchell - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital **Status:** RECRUITING **Zip:** PR2 9HT **Location 16:** **City:** Whitchurch **Contacts:** ***Contact 1:*** - **Name:** Carys Morgan - **Role:** CONTACT ***Contact 2:*** - **Name:** Carys Morgan - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United Kingdom **Facility:** Velindre University NHS Trust, Velindre Cancer Centre **Status:** NOT_YET_RECRUITING **Zip:** CF14 2TL #### Overall Officials **Official 1:** **Affiliation:** University of Oxford **Name:** Elizabeth Smyth **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Data access requests will be reviewed against specific eligibility criteria by the SCTU data custodian and key members of the trial team. **Description:** IPD will be made available, including data dictionaries, for approved data sharing requests. Individual participant data will be shared that underlie the results after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available. Pseudonymised participant data within the clinical trial dataset will be available for sharing via controlled access by authorised Southampton Clinical Trials Unit (SCTU) staff. The request for data access will need to detail the specific requirements and the proposed research, statistical analysis, publication plan and evidence of research group qualifications. Data will be shared once all parties have signed relevant data sharing documentation covering SCTU conditions for sharing and if required, an additional data sharing agreement from the sponsor. Proposals should be directed to ctu@soton.ac.uk. **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** Anonymous data will be available for request from 3 months after the publication of the results to researchers who provide a completed data sharing request form that describes a methodologically sound proposal, for the purpose of the approved proposal and if appropriate, signed a data-sharing agreement. **URL:** http://www.southampton.ac.uk/ctu/index.page? ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16064 - Name: Stomach Neoplasms - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M20497 - Name: Neoplasm, Residual - Relevance: LOW - As Found: Unknown - ID: T5486 - Name: Stomach Cancer - Relevance: LOW - As Found: Unknown - ID: T2141 - Name: Esophageal Cancer - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000018796 - Term: Immunoconjugates - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M325 - Name: Trastuzumab - Relevance: HIGH - As Found: Medication - ID: M233243 - Name: Trastuzumab deruxtecan - Relevance: HIGH - As Found: Corrected - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M29349 - Name: Topoisomerase I Inhibitors - Relevance: LOW - As Found: Unknown - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M20855 - Name: Immunoconjugates - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068878 - Term: Trastuzumab - ID: C000614160 - Term: Trastuzumab deruxtecan ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02512679 **Brief Title:** Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells **Official Title:** Protocol for Related Donor Hematopoietic Stem Cell Transplantation (HSCT) for Treatment of Symptomatic Genetic Lymphohematological Diseases #### Organization Study ID Info **ID:** CCI-06-00177 #### Organization **Class:** OTHER **Full Name:** Children's Hospital Los Angeles ### Status Module #### Completion Date **Date:** 2014-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-02-27 **Type:** ACTUAL **Last Update Submit Date:** 2017-01-12 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2013-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-06-17 **Type:** ESTIMATED **Results First Submit Date:** 2016-01-29 **Results First Submit QC Date:** 2016-05-11 #### Start Date **Date:** 2007-02 **Status Verified Date:** 2017-01 #### Study First Post Date **Date:** 2015-07-31 **Type:** ESTIMATED **Study First Submit Date:** 2015-05-21 **Study First Submit QC Date:** 2015-07-29 **Why Stopped:** Optimal dose obtained for engraftment and minimizing toxicity ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Lucile Packard Children's Hospital #### Lead Sponsor **Class:** OTHER **Name:** Children's Hospital Los Angeles #### Responsible Party **Investigator Affiliation:** Children's Hospital Los Angeles **Investigator Full Name:** Neena Kapoor, M.D. **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Many genetic diseases of lymphohematopoietic cells (such as sickle cell anemia, thalassemia, Diamond-Blackfan anemia, Combined Immune Deficiency (CID), Wiskott-Aldrich syndrome, chronic granulomatous disease, X-linked lymphoproliferative disease, and metabolic diseases affecting hematopoiesis) are sublethal diseases caused by mutations that adversely affect the development or function of different types of blood cells. Although pathophysiologically diverse, these genetic diseases share a similar clinical course of significant progressive morbidity, overall poor quality of life, and ultimate death from complications of the disease or its palliative treatment. Supportive care for these diseases includes chronic transfusion, iron chelation, and surgery (splenectomy or cholecystectomy) for the hemoglobinopathies; prophylactic antibiotics, intravenous immunoglobulin, and immunomodulator therapies for the immune deficiencies; and enzyme replacement injections and dietary restriction for some of the metabolic diseases. The suboptimal results of such supportive care measures have led to efforts to implement more aggressive therapeutic interventions to cure these lymphohematopoietic diseases. The most logical strategies for cure of these diseases have been either replacement of the patient's own hematopoietic stem cells (HSC) with those derived from a normal donor allogeneic bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT), or to genetically modify the patient's own stem cells to replace the defective gene (gene therapy). **Detailed Description:** The present study is to evaluate de-escalation of the cyclophosphamide (CY) dose in an innovative conditioning regimen with fludarabine and alemtuzumab as additional agents to achieve immunoablation, in combination with Busulfan (BU) to achieve myeloablation. Replacement of at least part of the cyclophosphamide dose by fludarabine in the conditioning regimen would be expected to maintain immunosuppression (and, therefore, engraftment) while reducing transplant-related complications (mucositis, hepatotoxicity, cardiotoxicity, pulmonary toxicity, hemorrhagic cystitis, mucositis, and possibly GVHD), thereby improving disease-free survival rates. Similarly, the potential benefits of alemtuzumab in the proposed conditioning regimen are increased rates of hematopoietic engraftment with less toxicity than that observed with cyclophosphamide, ultimately resulting in improved immune function and enhanced quality of life (12,13). A fludarabine/alemtuzumab-based, less intensive conditioning regimen with adequate immunosuppressive activity could conceivably allow more successful engraftment of stem cells from related donors in patients with genetic lymphohematological diseases, as well as lower rates of transplant-related mortality. Regimen-related toxicity is also believed to be a major contributing factor to GVHD (14). Therefore, conditioning regimens that cause less tissue injury may also lead to reduced GVHD. In the present study, the use of alemtuzumab in the conditioning regimen may be an added benefit, as this antibody causes T-cell depletion, thus, the risk of GVHD may also be reduced (15). The overall goal of the study is to improve the therapeutic index of HSCT by decreasing and, if possible, eliminating cyclophosphamide as a component of the pre-transplant conditioning for patients with genetic diseases of lymphohematopoiesis. The investigation will explore the risks and benefits of the proposed novel-conditioning regimen using a decreased dose of cyclophosphamide and additional immunosuppression with fludarabine and alemtuzumab to prevent graft rejection and recurrence of disease. The investigators will evaluate this regimen's impact on conditioning-related morbidity and mortality, and measure the success of the transplant procedure by engraftment and disease-free survival. If this regimen is able to successfully permit engraftment and reduce regimen-related toxicity, the next phase of treatment will test a further dose de-escalation for cyclophosphamide. It is anticipated that there will be four dose levels of cyclophosphamide in the overall study: 1) 105 mg/kg; 2) 70 mg/kg; 3) 35 mg/kg; and then finally, 4) 0 mg/kg. This study design was chosen to minimize study risks possibly associated with substitution of fludarabine and alemtuzumab for CY as immunoablation. The present protocol represents Level 1 in the study design; an amended protocol will be prepared prior to further de-escalation of the cyclophosphamide dose. ### Conditions Module **Conditions:** - Stem Cell Transplantation - Bone Marrow Transplantation - Peripheral Blood Stem Cell Transplantation - Allogeneic Transplantation - Genetic Diseases - Thalassemia - Pediatrics - Diamond-Blackfan Anemia - Combined Immune Deficiency - Wiskott-Aldrich Syndrome - Chronic Granulomatous Disease - X-linked Lymphoproliferative Disease - Metabolic Diseases **Keywords:** - Hematopoietic Stem Cell Transplantation Pediatrics, - stem cell transplantation - bone marrow transplantation - Peripheral Blood Stem Cell Transplantation - Allogeneic Transplantation - pediatrics - Combined Immune Deficiency - Chronic Granulomatous disease ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine **Intervention Names:** - Drug: Cyclophosphamide Dose Level 1 **Label:** Cyclophosphamide Dose Level 1 **Type:** OTHER #### Arm Group 2 **Description:** Cyclophosphamide given by intravenous (IV) at a total dose of 70 mg/kg (divided in two doses) given once a day for two days in combination with Busulfan, Campath and Fludarabine. **Intervention Names:** - Drug: Cyclophosphamide Dose Level 2 **Label:** Cyclophosphamide Dose Level 2 **Type:** OTHER #### Arm Group 3 **Description:** Cyclophosphamide given by intravenous (IV) at total does of 35 mg/kg as a one time dose in combination with Busulfan, Fludarabine and Campath **Intervention Names:** - Drug: Cyclophosphamide Dose Level 3 **Label:** Cyclophosphamide Dose Level 3 **Type:** OTHER #### Arm Group 4 **Description:** No cyclophosphamide given with Busulfan, Fludarabine and Campath **Intervention Names:** - Drug: Cyclophosphamide Dose Level 4 **Label:** Cyclophosphamide Dose Level 4 **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Cyclophosphamide Dose Level 1 **Description:** given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **Name:** Cyclophosphamide Dose Level 1 **Other Names:** - Cytoxan **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Cyclophosphamide Dose Level 2 **Description:** Level 2 will be 70mg/kg in 2 divided given once a day for 2 days; **Name:** Cyclophosphamide Dose Level 2 **Other Names:** - Cytoxan **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Cyclophosphamide Dose Level 3 **Description:** Level 3 will be 35mg/kg as a one-time dose. **Name:** Cyclophosphamide Dose Level 3 **Other Names:** - Cytoxan **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Cyclophosphamide Dose Level 4 **Description:** Level 4 will be no cytoxan. **Name:** Cyclophosphamide Dose Level 4 **Other Names:** - Cytoxan **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Absolute Neutrophil Count (ANC) =/\>500;(recovery of white cell count - self sustain platelet above 20,000 per cubic milimeter (20K) - evaluation by Chimerism Study (STR or FISH) at day +30 **Measure:** Number of Participants With Neutrophil Engraftment (=/>500 Cells/uL) and Platelet Engraftment (>20K Cell/uL) at 30 Days **Time Frame:** 30 days **Description:** assess rate of disease recurrence ("late relapse") due to autologous recovery of recipient hematopoiesis at one year post-HSCT. **Measure:** Number of Participants With Disease Recurrence at 1 Year Post-transplant **Time Frame:** 1 year **Description:** Assessment of conditioning regimen related toxicity was evaluated and documented with daily assessment during hospitalization and post-transplant follow-up up to one year. None of the subjects developed VOD necessitating any therapeutic intervention, severe mucositis, or toxicity of the Kidney, Liver or Gastrointestinal. **Measure:** Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant **Time Frame:** 1 year #### Secondary Outcomes **Description:** Clinical evaluation on a daily basis during hospitalization and at each post transplant clinical visit, up to one year, to determine incidence of acute and chronic graft-versus-host disease using Glucksberg grading scale. Acute graft-versus-host disease (aGVHD) develops within the first three months after transplantation and appears as a skin rash, often accompanied by hyperbilirubenemia, abnormal liver enzymes and gastrointestinal symptoms, as diarrhea, nausea and vomiting. Level of aGVHD is graded from 1-4. Chronic GVHD, typically a late complication of Blood and Marrow Transplantation (BMT) characterized by skin changes, sometimes sclerotic changes, with joint contractures, liver function abnormality, gastrointestinal symptoms and sometime other organ involvement such as eyes, lungs, and obliterative bronchiolitis (OB). Chronic GVHD is graded as absent, limited, or extensive. **Measure:** Number of Participants Who Developed Graft-Versus-Host-Disease (GVHD) as Determined by the Glucksberg Scale **Time Frame:** 1 yr **Description:** Evaluation for engraftment, correction of the disease, transplant related complications and event-free survival and overall survival of the subjects post-transplant was undertaken by standard measures and evaluation of disease with disease-specific testing. **Measure:** Number of Participants Who Were Disease Progression-Free and Death-Free at 1 Year Post-transplant **Time Frame:** 1 yr ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients with lethal or sublethal genetic lymphohematological disease (such as Hemaphagocytic lymphohistiocytosis (HLH) / Familial Erythrophagocytic Lymphohistiocytosis (FEL), Hurler's Syndrome, Hunter's Syndrome, Kostmann's Syndrome, Blackfan-Diamond Anemia, Chronic granulomatous Disease (CGD), Red Cell Aplasia, CID, Sickle Cell Anemia, Thalassemia, Adreno-leukodystrophy, metachromatic leukodystrophy, Wiskott-Aldrich Syndrome, X-Linked Lymphoproliferative Disease (XLD), Metabolic diseases affecting hematopoiesis, but not limited to), who are candidates for allogeneic transplantation for their disease and have a histocompatible sibling or related donor, ages 0 to 21 years, will be candidates for this study protocol. The suitable related donor is a 10/10 or 9/10 allele Human Leukocyte Antigen (HLA) match with the patient. All patients who have previously had serious life- threatening events due to disease process may be included in the study. Patients must have adequate physical function and vital organ function to tolerate transplant procedure, as measured by: * Cardiac: Shortening fraction \>26% or left ventricular ejection fraction at rest must be \> 40%. * Hepatic: Bilirubin, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) \< 3x upper limit of normal (as per local laboratory) for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome). * Renal: Serum creatinine \< 2x upper limit of normal for age or if serum creatinine elevated beyond normal range patient must have creatinine Clearance or Glomerular filtration rate (GFR) \>50% lower limit of normal for age. * Pulmonary: Forced expiratory volume (FEV)1, Forced Vital Capacity (FVC), and Diffusing Lung Capacity for Carbon Monoxide (DLCO) (corrected for Hgb) \> 50% predicted. For patients where pulse oximetry is performed, O2 saturation \> 92% * Evaluation of iron status in patients who have received more than 12 red cell transfusions. Measurements of serum ferritin levels and MRI of the liver and heart tissue will evaluate the iron stores. If high iron load is identified in these organs further evaluation will be done to determine the suitability as transplant recipient. Should these studies indicate that chelation is necessary the following should apply: That the treating hematologist will provide the specific chelation type and timing. Evaluation of organ iron load will be part of the HSCT work-up and if high iron load is identified then the BMT team will work with the hematologist attending in developing a plan for the patient. Exclusion Criteria: * Karnofsky performance status \< 70%, or Lansky \< 40% for patients \< 16 years old. * Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress). * Seropositivity for the human immunodeficiency virus (HIV). * Acute active hepatitis. * Diagnosis of end-organ dysfunction that precludes the ability to tolerate the transplant procedure. * Patients with a diagnosis of Fanconi Anemia are excluded. **Minimum Age:** 3 Months **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Children's Hospital Los Angeles **Name:** Neena Kapoor, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Tranplant data is reported to CIBMTR and is available to the other investigators **IPD Sharing:** YES ### References Module #### References **Citation:** Mahadeo KM, Weinberg KI, Abdel-Azim H, Miklos DB, Killen R, Kohn D, Crooks GM, Shah AJ, Kharbanda S, Agarwal R, Kapoor N. A reduced-toxicity regimen is associated with durable engraftment and clinical cure of nonmalignant genetic diseases among children undergoing blood and marrow transplantation with an HLA-matched related donor. Biol Blood Marrow Transplant. 2015 Mar;21(3):440-4. doi: 10.1016/j.bbmt.2014.11.005. Epub 2014 Nov 13. **PMID:** 25459642 #### See Also Links **Label:** Reduced-toxicity regimen for related HSCT transplants **URL:** http://www.ncbi.nlm.nih.gov/pubmed?term=%22Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation%22%5BJour%5D+AND+21%5Bvolume%5D+AND+Mahadeo%5Bauthor%5D&cmd=detailssearch ## Derived Section ### Condition Browse Module - Ancestors - ID: D000000745 - Term: Anemia, Hemolytic, Congenital - ID: D000000743 - Term: Anemia, Hemolytic - ID: D000000740 - Term: Anemia - ID: D000006402 - Term: Hematologic Diseases - ID: D000006453 - Term: Hemoglobinopathies - ID: D000007154 - Term: Immune System Diseases - ID: D000008206 - Term: Lymphatic Diseases - ID: D000010335 - Term: Pathologic Processes - ID: D000010585 - Term: Phagocyte Bactericidal Dysfunction - ID: D000007960 - Term: Leukocyte Disorders - ID: D000040181 - Term: Genetic Diseases, X-Linked - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000029502 - Term: Anemia, Hypoplastic, Congenital - ID: D000000741 - Term: Anemia, Aplastic - ID: D000012010 - Term: Red-Cell Aplasia, Pure - ID: D000080984 - Term: Congenital Bone Marrow Failure Syndromes - ID: D000080983 - Term: Bone Marrow Failure Disorders - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000025861 - Term: Blood Coagulation Disorders, Inherited - ID: D000001778 - Term: Blood Coagulation Disorders - ID: D000008231 - Term: Lymphopenia - ID: D000007970 - Term: Leukopenia - ID: D000095542 - Term: Cytopenia - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000081207 - Term: Primary Immunodeficiency Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M4070 - Name: Anemia - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: HIGH - As Found: Metabolic Diseases - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: HIGH - As Found: X-linked Lymphoproliferative Disease - ID: M16557 - Name: Thalassemia - Relevance: HIGH - As Found: Thalassemia - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: HIGH - As Found: Immune Deficiency - ID: M9208 - Name: Granulomatous Disease, Chronic - Relevance: HIGH - As Found: Chronic Granulomatous Disease - ID: M23456 - Name: Anemia, Diamond-Blackfan - Relevance: HIGH - As Found: Diamond Blackfan Anemia - ID: M17662 - Name: Wiskott-Aldrich Syndrome - Relevance: HIGH - As Found: Wiskott-Aldrich Syndrome - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: HIGH - As Found: Genetic Diseases - ID: M9547 - Name: Hemolysis - Relevance: LOW - As Found: Unknown - ID: M4073 - Name: Anemia, Hemolytic - Relevance: LOW - As Found: Unknown - ID: M4075 - Name: Anemia, Hemolytic, Congenital - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9539 - Name: Hemoglobinopathies - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M13493 - Name: Phagocyte Bactericidal Dysfunction - Relevance: LOW - As Found: Unknown - ID: M10963 - Name: Leukocyte Disorders - Relevance: LOW - As Found: Unknown - ID: M24877 - Name: Genetic Diseases, X-Linked - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M23455 - Name: Anemia, Hypoplastic, Congenital - Relevance: LOW - As Found: Unknown - ID: M4071 - Name: Anemia, Aplastic - Relevance: LOW - As Found: Unknown - ID: M14852 - Name: Red-Cell Aplasia, Pure - Relevance: LOW - As Found: Unknown - ID: M2241 - Name: Bone Marrow Failure Disorders - Relevance: LOW - As Found: Unknown - ID: M13118 - Name: Pancytopenia - Relevance: LOW - As Found: Unknown - ID: M2242 - Name: Congenital Bone Marrow Failure Syndromes - Relevance: LOW - As Found: Unknown - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M23095 - Name: Blood Coagulation Disorders, Inherited - Relevance: LOW - As Found: Unknown - ID: M11224 - Name: Lymphopenia - Relevance: LOW - As Found: Unknown - ID: M10973 - Name: Leukopenia - Relevance: LOW - As Found: Unknown - ID: M3170 - Name: Cytopenia - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M2285 - Name: Primary Immunodeficiency Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T5622 - Name: Thalassemia - Relevance: HIGH - As Found: Thalassemia - ID: T1304 - Name: Chronic Granulomatous Disease - Relevance: HIGH - As Found: Chronic Granulomatous Disease - ID: T5990 - Name: X-linked Lymphoproliferative Syndrome - Relevance: HIGH - As Found: X-linked Lymphoproliferative Disease - ID: T1837 - Name: Diamond-Blackfan Anemia - Relevance: HIGH - As Found: Diamond Blackfan Anemia - ID: T5939 - Name: Wiskott Aldrich Syndrome - Relevance: HIGH - As Found: Wiskott-Aldrich Syndrome - ID: T4833 - Name: Pure Red Cell Aplasia - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013789 - Term: Thalassemia - ID: D000006105 - Term: Granulomatous Disease, Chronic - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000029503 - Term: Anemia, Diamond-Blackfan - ID: D000014923 - Term: Wiskott-Aldrich Syndrome - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000008659 - Term: Metabolic Diseases - ID: D000007153 - Term: Immunologic Deficiency Syndromes ### Intervention Browse Module - Ancestors - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018501 - Term: Antirheumatic Agents - ID: D000018906 - Term: Antineoplastic Agents, Alkylating - ID: D000000477 - Term: Alkylating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000019653 - Term: Myeloablative Agonists ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents ### Intervention Browse Module - Browse Leaves - ID: M16759 - Name: Tin Fluorides - Relevance: LOW - As Found: Unknown - ID: M6727 - Name: Cyclophosphamide - Relevance: HIGH - As Found: Cycle - ID: M283230 - Name: Fludarabine - Relevance: LOW - As Found: Unknown - ID: M5336 - Name: Busulfan - Relevance: LOW - As Found: Unknown - ID: M225513 - Name: Fludarabine phosphate - Relevance: LOW - As Found: Unknown - ID: M1347 - Name: Alemtuzumab - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M20942 - Name: Antineoplastic Agents, Alkylating - Relevance: LOW - As Found: Unknown - ID: M3820 - Name: Alkylating Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003520 - Term: Cyclophosphamide ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Cyclophosphamide Dose Level 1 **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** EG000 **Other Num Affected:** 7 **Other Num at Risk:** 20 **Serious Number Affected:** 2 **Serious Number At Risk:** 20 **Title:** Cyclophosphamide Dose Level 1 **Frequency Threshold:** 0 #### Other Events **Term:** Cytomegalovirus (CMV) infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Re-activation of cytomegalovirus (CMV) in 5/20 enrolled subjects documented by blood CMV Polymerase Chain Reaction (PCR) test. **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** Viral Infection **Term:** Epstein-Barr Virus (EBV) **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Epstein-Barr Virus (EBV) was documented to be positive in 1/20 subjects enrolled in the study; confirmed by Polymerase Chain Reaction (PCR). **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** Viremia, Epstein-Bar **Term:** Adenovirus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Adenovirus was detected in one (1) enrolled subject by blood PCR. **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** Adenovirus #### Serious Events **Term:** Death due to pre-exisiting mucormycosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Subject had pretransplant history of mucormycosis infection. Patient was received anti-fungal medications. **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** Fungal infection ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Death due to interstitial pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Subject developed interstitial pneumonia on Day +187 post transplant. Onset thought to be community acquired pneumonia. **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** Pneumonia ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Time Frame:** Adverse event data was collected throughout the course of the study up to 2 years post transplantation. Subjects were evaluated for post transplant complications related to conditioning, such as VOD, GVHD, infections and engraftment failure. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 20 **Units:** Participants ### Group **ID:** BG000 **Title:** Cyclophosphamide Dose Level 1 **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. ### Measure #### Measurement **Group ID:** BG000 **Value:** 19 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** .4 **Upper Limit:** 26 **Value:** 2.3 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 7 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Description:** Deviation from study protocol - enrollment of 26-year-old subject with pediatric disease. Subject's data included in outcome measurements/analysis. **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Gender **Unit of Measure:** Participants ### Measure 4 **Description:** Enrollment of participants was conducted in California. **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** De-escalation was not ensued. All enrolled subjects engrafted without toxicity for dose level one. ### Point of Contact **Email:** nkapoor@chla.usc.edu **Organization:** Children's Hospital Los Angeles **Phone:** 343-361-2434 **Title:** Neena Kapoor, M.D. ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Absolute Neutrophil Count (ANC) =/\>500;(recovery of white cell count - self sustain platelet above 20,000 per cubic milimeter (20K) - evaluation by Chimerism Study (STR or FISH) at day +30 **Parameter Type:** NUMBER **Population Description:** Subject enrolled and received Dose Level 1 of Cyclophosphamide and engrafted with Absolute Neutrophil Count (ANC) =/\>500;(recovery of white cell count - self sustain platelet above 20k - evaluation by Chimerism Study (STR or FISH) at day +30. **Reporting Status:** POSTED **Time Frame:** 30 days **Title:** Number of Participants With Neutrophil Engraftment (=/>500 Cells/uL) and Platelet Engraftment (>20K Cell/uL) at 30 Days **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** OG000 **Title:** Cyclophosphamide Dose Level 1 #### Outcome Measure 2 **Description:** assess rate of disease recurrence ("late relapse") due to autologous recovery of recipient hematopoiesis at one year post-HSCT. **Parameter Type:** NUMBER **Population Description:** All subjects who received dose level 1 of Cyclophosphamide did not experience re-occurrence of disease. **Reporting Status:** POSTED **Time Frame:** 1 year **Title:** Number of Participants With Disease Recurrence at 1 Year Post-transplant **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** OG000 **Title:** Cyclophosphamide Dose Level 1 #### Outcome Measure 3 **Description:** Assessment of conditioning regimen related toxicity was evaluated and documented with daily assessment during hospitalization and post-transplant follow-up up to one year. None of the subjects developed VOD necessitating any therapeutic intervention, severe mucositis, or toxicity of the Kidney, Liver or Gastrointestinal. **Parameter Type:** NUMBER **Population Description:** Subjects who received dose level 1 of Cyclophosphamide did not experience veno-occlusive disease, organ failure or severe mucositis. **Reporting Status:** POSTED **Time Frame:** 1 year **Title:** Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** OG000 **Title:** Cyclophosphamide Dose Level 1 #### Outcome Measure 4 **Description:** Clinical evaluation on a daily basis during hospitalization and at each post transplant clinical visit, up to one year, to determine incidence of acute and chronic graft-versus-host disease using Glucksberg grading scale. Acute graft-versus-host disease (aGVHD) develops within the first three months after transplantation and appears as a skin rash, often accompanied by hyperbilirubenemia, abnormal liver enzymes and gastrointestinal symptoms, as diarrhea, nausea and vomiting. Level of aGVHD is graded from 1-4. Chronic GVHD, typically a late complication of Blood and Marrow Transplantation (BMT) characterized by skin changes, sometimes sclerotic changes, with joint contractures, liver function abnormality, gastrointestinal symptoms and sometime other organ involvement such as eyes, lungs, and obliterative bronchiolitis (OB). Chronic GVHD is graded as absent, limited, or extensive. **Parameter Type:** NUMBER **Population Description:** Subjects who received dose level 1 of Cyclophosphamide were revaluated for graft-versus-host disease (GVHD) post transplantation. **Reporting Status:** POSTED **Time Frame:** 1 yr **Title:** Number of Participants Who Developed Graft-Versus-Host-Disease (GVHD) as Determined by the Glucksberg Scale **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** OG000 **Title:** Cyclophosphamide Dose Level 1 #### Outcome Measure 5 **Description:** Evaluation for engraftment, correction of the disease, transplant related complications and event-free survival and overall survival of the subjects post-transplant was undertaken by standard measures and evaluation of disease with disease-specific testing. **Parameter Type:** NUMBER **Population Description:** Subjects receiving dose level 1 of Cyclophosphamide event free survival post transplant at 100 days was 95% and 90% 1 year. **Reporting Status:** POSTED **Time Frame:** 1 yr **Title:** Number of Participants Who Were Disease Progression-Free and Death-Free at 1 Year Post-transplant **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** OG000 **Title:** Cyclophosphamide Dose Level 1 ### Participant Flow Module #### Group **Description:** Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** FG000 **Title:** Cyclophosphamide Dose Level 1 #### Group **Description:** De-escalation of Cyclophosphamide given by Intravenous (IV) at a total dose of 70 mg/kg, to be divided into two doses of one 35 mg/kg dose per day, for 2 days Drug to be given in combination of Busulfan, Campath and Fludarabine Cyclophosphamide Dose Level 1: given by IV at a total dose of 75 mg/kg, to be divided into two doses of one 35 mg/kg dose per day, for 2 days. After ten patients the de-escalation will begin if the stopping rule is not met. **ID:** FG001 **Title:** Cyclophosphamide Dose Level 2 #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Pre-Assignment Details:** This is a sequential dose de-escalation of Cyclophosphamide with first at 105 mg/kg total dose compared to standard 200mg/kg total dose (Arm 1). Prior to enrollment patients had to meet all eligibility criteria for allogeneic transplantation. Study closed after 1st level because all patients engrafted and none had toxicity related to transplant. **Recruitment Details:** Patients for bone marrow transplantation who met the eligibility criteria of diagnosis and clinical status and had histocompatible sibling donor. These patients were recruited at Children's Hospital Los Angeles and Lucille Packard Children's Hospital at Stanford University. Patients were recruited between 2006 and 2013. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT06224179 **Acronym:** U/STAP **Brief Title:** Role of Ultrasound Guided Transversus Abdominis Plane Block in Pain Control After Hepatectomy **Official Title:** Ultrasound Guided Oblique Subcostal Transversus Abdominis Plane Block(TAP) Versus Both Subcostal and Posterior TAP Block as Postoperative Analgesia in Hepatectomy #### Organization Study ID Info **ID:** M S 96/2021 #### Organization **Class:** OTHER **Full Name:** Ain Shams University ### Status Module #### Completion Date **Date:** 2024-06-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-30 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-29 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-05-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-02-01 **Type:** ESTIMATED **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2024-01-25 **Type:** ACTUAL **Study First Submit Date:** 2024-01-17 **Study First Submit QC Date:** 2024-01-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ain Shams University #### Responsible Party **Investigator Affiliation:** Ain Shams University **Investigator Full Name:** Ahmed wagih Ezzat deusouky **Investigator Title:** lecturer of anesthesia **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Inadequately managed acute pain following abdominal surgery originates from somatic pain signals in the abdominal wall and is linked to various unfavorable postoperative outcomes. These consequences encompass patient distress, respiratory complications, delirium, myocardial ischemia, extended hospital stays, an elevated risk of chronic pain, heightened analgesic consumption, delayed bowel function, and an increased need for rescue analgesics. This study aims to assess the postoperative analgesic efficacy of ultrasound-guided Transversus Abdominis Plane (TAP) block using oblique subcostal and posterior approaches in hepatectomy. **Detailed Description:** Pain control is vital to achieve enhanced recovery after abdominal surgeries . TAP block had been demonstrated to improve pain related outcomes after abdominal surgeries. Postoperative pain management for patients undergoing hepatic resection is a challenge due to the risk of perioperative liver dysfunction.TAP block is a promising regional analgesic technique. This study aimed to evaluate the effect of US-guided subcostal approach versus combination of both subcostal and posterior approaches of TAP block The patients will be randomly divided into two groups : group A will recieve oblique subcostal TAP block and group B will recieve both subcostal and posterior TAP block . ### Conditions Module **Conditions:** - Analgesia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Group A received ultrasound guided subcostal TAP block with 30 ml of local anesthetics and additives **Intervention Names:** - Procedure: ultrasound guided subcostal TAP block **Label:** Group A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Group B received ultrasound guided both subcostal and posterior TAP block with 30 ml of local anesthetics and additives at each side **Intervention Names:** - Procedure: ultrasound guided combined posterior and subcostal TAP block **Label:** Group B **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Group A **Description:** patients will be randomly divided into two groups using a computer generated random number chart. Group A received ultrasound guided subcostal TAP block, **Name:** ultrasound guided subcostal TAP block **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Group B **Description:** patients will be randomly divided into two groups using a computer generated random number chart. Group B received ultrasound guided combined posterior and subcostal TAP block, **Name:** ultrasound guided combined posterior and subcostal TAP block **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Pain will be assessed on admission and at 2, 4, 8, 12 and 24 hours at rest and with passive flexion of hip and knee joint using visual analogue scale (VAS) ranging from 0 for no pain to 10 for worst pain. **Measure:** postoperative analgesia (VAS) during the 1st 24 hours in ICU **Time Frame:** 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ASA I and II patients. aged 18 to 50 years. 70 to 80 kg. Exclusion Criteria: * patients under 18 years of age. * History of Allergic reactions to study drugs. * Opioid or analgesic abuse, and chronic treatment with opioids, or non-steroidal anti-inflammatory drugs. * History of bleeding tendency or coagulopathy . **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** a_wagih82@yahoo.com **Name:** Ahmed El-Dolah, lecturer of Anesthesia **Phone:** +20111113077 **Role:** CONTACT ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02901379 **Brief Title:** Effect of 80-mg Atorvastatin on Myocardial Edema **Official Title:** Effect of 80-mg Atorvastatin on Myocardial Edema Following Coronary Artery Bypass Surgery in Relation With Follistatin-Like Protein-1 #### Organization Study ID Info **ID:** LB.02.01/VII/090/KEP.013/2016 #### Organization **Class:** OTHER **Full Name:** National Cardiovascular Center Harapan Kita Hospital Indonesia ### Status Module #### Completion Date **Date:** 2018-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-08-23 **Type:** ACTUAL **Last Update Submit Date:** 2018-08-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-08 **Type:** ACTUAL #### Start Date **Date:** 2016-10 **Status Verified Date:** 2018-08 #### Study First Post Date **Date:** 2016-09-15 **Type:** ESTIMATED **Study First Submit Date:** 2016-09-06 **Study First Submit QC Date:** 2016-09-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** National Cardiovascular Center Harapan Kita Hospital Indonesia #### Responsible Party **Investigator Affiliation:** National Cardiovascular Center Harapan Kita Hospital Indonesia **Investigator Full Name:** Rita Zahara **Investigator Title:** Cardiologist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to determine whether atorvastatin 80mg can reduce the development of myocardial edema following coronary artery bypass surgery. This study also want to determine: 1. whether atorvastatin 80mg can influence Follistatin-like 1 (FSTL1) plasma level following bypass surgery? 2. whether there is correlation between myocardial edema and FSTL1 plasma level? 3. the efficacy of atorvastatin 80mg compared to atorvastatin 10mg in reducing hs-CRP (high sensitive-C reactive protein) and MDA (malondialdehyde) plasma level following bypass surgery? 4. the efficacy of atorvastatin 80mg compared to atorvastatin 10mg in raising PKA and PKB plasma level following bypass surgery? **Detailed Description:** This study is an double blinded experimental study using parallel design. Study subjects are patients in Harapan Kita hospital who are registered to CABG (Coronary Artery Bypass Graft) surgery and fulfill all the eligibility criteria. The subjects will be first consecutively selected, with male age 40-65 as the criteria. After that the investigators do the randomization with block randomization method. All the subjects will be given drug with label A and label B (only the pharmacist know the which dose of atorvastatin belong to which label). Total subjects needed for this study are 30 (15 belong to study group and 15 belong to control group) MRI (Magnetic Resonance Imaging) results will be read by two radiologists, and analyzed using cronbach alpha. The results are considered equal if the cronbach \>0,7. If it is proven to be unequal, then the third radiologist will decide. Statin is known to have several adverse effects, such as myopathy, myositis to rhabdomyolysis, elevated liver enzyme, memory loss, GI (gastrointestinal) disturbance, and severa others. Therefore, the investigators will check baseline CK (creatine kinase) and liver enzyme at the beginning of the study, before the surgery, and if the patient feel any symptoms. Statin will be stopped if patient decide to stop, or if there is increase in ALT (alanine aminotransferase) higher that three time upper normal value, or if there is increase in CK higher than ten times upper normal value. Statistical analysis using IBM SPSS statistics version 21.0. Comparative analysis for variables such as smoking history, obesity, hypertension, dyslipidemia, diabetes, family history, infarct history, ACE-I/ARB (angiotensin converting enzyme inihibitor /angiotensin receptor blocker) therapy will be using chi-square or fischer. Comparative analysis for variables T2 relaxation time, FSTL1, hs-CRP, PKA (protein kinase A), PKB (Protein Kinase B), MDA, age, CPB (Cardiopulmonary Bypass) time, CABG time will using unpaired t-test or Mann-whitney. Correlative analysis between FSTL1 and T2 relaxation time will be using Pearson test. ### Conditions Module **Conditions:** - Myocardial Edema **Keywords:** - atorvastatin - myocardial edema - Follistatin-like 1 - FSTL1 - atorvastatin 80mg - coronary artery bypass surgery ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects who will receive atorvastatin 80mg for two weeks **Intervention Names:** - Drug: Atorvastatin 80mg **Label:** Atorvastatin 80mg **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subject who will receive atorvastatin 10mg **Intervention Names:** - Drug: Atorvastatin 10mg **Label:** Atorvastatin 10mg **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Atorvastatin 80mg **Description:** Subject will be given atorvastatin 80mg for two weeks **Name:** Atorvastatin 80mg **Other Names:** - Lipitor **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Atorvastatin 10mg **Description:** Subjects will be give atorvastatin 10mg as part of standard therapy in hospital **Name:** Atorvastatin 10mg **Other Names:** - Lipitor **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** T2 relaxation time (in ms) difference between control and study group **Measure:** T2 relaxation time **Time Frame:** day 6 after CABG #### Secondary Outcomes **Description:** FSTL1 plasma level difference between control and study group **Measure:** FSTL1 plasma level **Time Frame:** day 6 after CABG **Description:** PKA plasma level difference between control and study group **Measure:** PKA plasma level **Time Frame:** day 6 after CABG **Description:** PKB plasma level difference between control and study group **Measure:** PKB plasma level **Time Frame:** day 6 after CABG **Description:** hs-CRP plasma level difference between control and study group **Measure:** hs-CRP plasma level **Time Frame:** day 1 after CABG **Description:** MDA plasma level difference between control and study group **Measure:** MDA plasma level **Time Frame:** day 1 after CABG **Measure:** Change from baseline FSTL1 plasma level **Time Frame:** day 1 and day 6 after CABG **Measure:** Change from baseline PKA plasma level **Time Frame:** day 1 and day 6 after CABG **Measure:** Change from baseline PKB plasma level **Time Frame:** day 1 and day 6 after CABG ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with coronary artery disease indicated for CABG surgery * has signed informed consent Exclusion Criteria: * high risk EURO (European System for Cardiac Operative Risk Evaluation) score * creatinin value\>2 g/dl * direct bilirubin value \>3 mg/ml * AST/ALT (aspartate transaminase / alanine transaminase) value \>1,5 times UNL (upper normal limit) * high pre-operative CKMB (Creatine Kinase-MB) and troponin * LVEF (Left Ventricular Ejection Fraction) \<45% * concomitant valve disease required surgery * contraindicated for MRI * high degree ventricular arrhytmia * coagulation disorder * COPD (chronic obsructive pulmonary disease) * HIV (Human Immunodeficiency Virus) +, HBV (Hepatitis B Virus)+, HCV (Hepatitis C Virus) + * conduction abnormality, pacemaker * electrolyte or blood gas disturbance * receiving immunosuppressive drug or cytotoxic agent 4 weeks before surgery * receiving macrolide, azole antifungal, fibrate, or protease inhibitor HIV drug **Maximum Age:** 65 Years **Minimum Age:** 40 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** National Cardiovascular Center Harapan Kita **Name:** Rita Zahara **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7657 - Name: Edema - Relevance: HIGH - As Found: Edema ### Condition Browse Module - Meshes - ID: D000004487 - Term: Edema ### Intervention Browse Module - Ancestors - ID: D000000924 - Term: Anticholesteremic Agents - ID: D000000960 - Term: Hypolipidemic Agents - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000057847 - Term: Lipid Regulating Agents - ID: D000019161 - Term: Hydroxymethylglutaryl-CoA Reductase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M351 - Name: Atorvastatin - Relevance: HIGH - As Found: Of each - ID: M4243 - Name: Anticholesteremic Agents - Relevance: LOW - As Found: Unknown - ID: M4278 - Name: Hypolipidemic Agents - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M28883 - Name: Lipid Regulating Agents - Relevance: LOW - As Found: Unknown - ID: M21155 - Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069059 - Term: Atorvastatin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02590679 **Acronym:** Venus-P **Brief Title:** Multi-center Trial of Percutaneous Pulmonary Valve Implantation With Venus-p **Official Title:** Multi-center Trial of Percutaneous Pulmonary Valve Implantation Using Venus-P Valve for Patients With Severe Pulmonary Regurgitation and Native Right Ventricular Outflow Tract After Previous Surgical Repair #### Organization Study ID Info **ID:** PPVI-2013 #### Organization **Class:** OTHER **Full Name:** Shanghai Zhongshan Hospital ### Status Module #### Completion Date **Date:** 2017-02 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2015-10-29 **Type:** ESTIMATED **Last Update Submit Date:** 2015-10-28 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-07 **Type:** ESTIMATED #### Start Date **Date:** 2013-05 **Status Verified Date:** 2015-10 #### Study First Post Date **Date:** 2015-10-29 **Type:** ESTIMATED **Study First Submit Date:** 2015-10-15 **Study First Submit QC Date:** 2015-10-28 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Fu Wai Hospital, Beijing, China **Class:** OTHER **Name:** Huaxi Hospital **Class:** OTHER **Name:** Shanghai Chest Hospital **Class:** OTHER **Name:** Shanghai Children's Medical Center #### Lead Sponsor **Class:** OTHER **Name:** Shanghai Zhongshan Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Venus-P Valve (Venus Medtech, Shanghai, China) is the first self-expandable interventional Pulmonary Valve, which is composed of a Nitinol multilevel support frame with a tri-leaflet porcine pericardial tissue valve, and a 14-22 Fr delivery catheter. The purpose of the multi-center trial is to evaluate the safety and efficacy of the Venus-P Valve for percutaneous pulmonary valve implantation (PPVI) in patients pulmonary regurgitation and native right ventricular outflow tract (RVOT) after surgical repair of RVOT. **Detailed Description:** Clinical experience to date with transcatheter pulmonary valve replacement has been limited to two balloon expandable systems, namely the Melody Valve (Medtronic Inc, Minneapolis, MN) and the Sapien valve (Edwards Lifesciences, Irvine, CA). Both valves have undergone clinical trials with good medium-term valve durability. Although both the Melody and the Sapien valves have been used in native outflow tracts with good success , limitations to the extended application of these valves have generally centered on the maximum diameter of the RVOT. Indeed in the majority of patients requiring pulmonary valve replacement (PVR), these balloon expandable systems are not large enough to maintain stable valve position within the dilated native RVOT.Therefore more recent efforts have concentrated on a self-expanding system to provide valve competence despite significant dilation of the native RVOT. Venus-P Valve (Venus Medtech, Shanghai, China) is the first self-expandable interventional Pulmonary Valve, which is composed of a Nitinol multilevel support frame with a tri-leaflet porcine pericardial tissue valve, and a 14-22 Fr delivery catheter. The purpose of the trial is to evaluate the safety and efficacy of the Venus-P Valve for PPVI in patients pulmonary regurgitation and native RVOT after surgical repair of RVOT. ### Conditions Module **Conditions:** - Pulmonary Regurgitation - Tetralogy of Fallot ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 44 **Type:** ESTIMATED **Phases:** - PHASE2 - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** pulmonary regurgitation after surgical repair of congenital right ventricular outflow tract **Intervention Names:** - Device: Venues-P Valve **Label:** PRAS **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - PRAS **Description:** a Novel Self-Expanding Percutaneous Stent-Valve in the Native Right Ventricular Outflow Tract **Name:** Venues-P Valve **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** right ventricular end diastolic volume index **Time Frame:** 6 months #### Secondary Outcomes **Description:** death, severe arrhythmia, pericardial tamponade, emergency surgery, RVOT rupture, pulmonary artery perforation, cardiac shock, endocarditis, bleeding , and other complications caused by procedure **Measure:** Incidence of adverse cardiovascular events **Time Frame:** 48 hours **Description:** All cause deaths (cardiac death, and non cardiac death) or strokes **Measure:** Incidence of deaths or strokes **Time Frame:** 12 months **Description:** Max pressure gradient (PG) **Measure:** pulmonary pressure gradient **Time Frame:** 1,3,6,12 months **Measure:** grade of pulmonary regurgitation **Time Frame:** 1,3,6,12 months **Measure:** New York Heart Association (NYHA) class **Time Frame:** 1,3,6,12 months **Measure:** 6 minutes walk distance **Time Frame:** 1,3,6,12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Moderate to severe pulmonary regurgitation after surgical repair of congenital right ventricular outflow tract obstruction with trans-annulus or RVOT patch; 2. right ventricular diastolic volume index: 130-160 mL/m2 measured by isotopic examination or cardiac MRI measurements; 3. Age: ≥10 years and ≤60 years; 4. Weight ≥18 Kg; 5. Pulmonary annulus : 14- 31 mm; 6. RVOT length ≥20mm ; 7. Signing the informed consent; 8. Any of the following conditions: ① symptomatic, ②progressive RV systolic dysfunction, ③ progressive tricuspid regurgitation (at least moderate), ④ RVOT obstruction with RV systolic pressure ≥80 mmHg, ⑤ Sustained atrial/ventricular arrhythmias. Exclusion Criteria: 1. Pre-existing pulmonary artery stenosis or artificial pulmonary valve at any position; 2. Severe chest wall deformity (funnel chest, etc.); 3. Acute uncompensated heart failure; 4. Active infection or endocarditis requiring antibiotic therapy; 5. Leukopenia (white blood cell \<3000 mm3); 6. Acute or chronic anemia (hemoglobin \<9 g/L); 7. Platelet counts \<10000 /mm3; 8. Impossibly of delivering Venus-P to RVOT as judged by researcher s before procedure; 9. Known allergy to aspirin or heparin; 10. Positive urine or serum pregnancy test in female subjects. **Maximum Age:** 60 Years **Minimum Age:** 10 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** peden@sina.com **Name:** Wenzhi Pan, M.D. **Role:** CONTACT #### Locations **Location 1:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Email:** peden@sina.com - **Name:** Wenzhi Pan, M.D. - **Role:** CONTACT **Country:** China **Facility:** Zhongshan Hopital of Fudan University **State:** Shanghai **Status:** RECRUITING **Zip:** 200032 **Location 2:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Name:** Gejun Zhang, M.D. - **Role:** CONTACT **Country:** China **Facility:** Beijing Fuwai Hospital **Status:** RECRUITING **Location 3:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Name:** Xin Pan, M.D. - **Role:** CONTACT **Country:** China **Facility:** Shanghai Chest Hospital **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Fudan University **Name:** Junbo Ge, M.D. **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Cao QL, Kenny D, Zhou D, Pan W, Guan L, Ge J, Hijazi ZM. Early clinical experience with a novel self-expanding percutaneous stent-valve in the native right ventricular outflow tract. Catheter Cardiovasc Interv. 2014 Dec 1;84(7):1131-7. doi: 10.1002/ccd.25544. Epub 2014 May 28. **PMID:** 24824357 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006330 - Term: Heart Defects, Congenital - ID: D000018376 - Term: Cardiovascular Abnormalities - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006331 - Term: Heart Diseases - ID: D000000013 - Term: Congenital Abnormalities - ID: D000006349 - Term: Heart Valve Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16539 - Name: Tetralogy of Fallot - Relevance: HIGH - As Found: Tetralogy of Fallot - ID: M14519 - Name: Pulmonary Valve Insufficiency - Relevance: HIGH - As Found: Pulmonary Regurgitation - ID: M9418 - Name: Heart Defects, Congenital - Relevance: LOW - As Found: Unknown - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M20503 - Name: Cardiovascular Abnormalities - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M9437 - Name: Heart Valve Diseases - Relevance: LOW - As Found: Unknown - ID: T5613 - Name: Tetralogy of Fallot - Relevance: HIGH - As Found: Tetralogy of Fallot ### Condition Browse Module - Meshes - ID: D000013771 - Term: Tetralogy of Fallot - ID: D000011665 - Term: Pulmonary Valve Insufficiency ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05974579 **Brief Title:** Safety and Dosimetry of a New Radiotracer to Detect Misfolded SOD1 Associated With Amyotrophic Lateral Sclerosis **Official Title:** A Single Center, Open Label Study to Evaluate Biodistribution, Pharmacokinetics and Safety of [89Zr]Zr-DFO-AP-101 PET (Positron Emission Tomography) in Healthy Volunteers and Amyotrophic Lateral Sclerosis (ALS) Patients #### Organization Study ID Info **ID:** 2024-5148 #### Organization **Class:** OTHER **Full Name:** Université de Sherbrooke #### Secondary ID Infos **Domain:** CIUSSS de l'Estrie - CHUS **ID:** 2024-5148 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2024-07-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-29 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-05-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-11-23 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2023-08-03 **Type:** ACTUAL **Study First Submit Date:** 2023-07-11 **Study First Submit QC Date:** 2023-07-26 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Eli Lilly and Company **Class:** INDUSTRY **Name:** Chorus Wellness Inc. **Class:** UNKNOWN **Name:** AL-S Pharma AG #### Lead Sponsor **Class:** OTHER **Name:** Université de Sherbrooke #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant disease progression before formal diagnosis. An imaging test for early detection of ALS and for monitoring disease progression would have significant diagnostic and prognostic value. PET imaging with an appropriate radiotracer has great potential as a biomarker for ALS given that it would permit visualization of central nervous system (CNS) pathology in individuals living with the disease. To that extent, the primary goal of this phase I study is evaluating the safety and biodistribution of the new tracer \[89Zr\]Zr-DFO-AP-101 in healthy volunteers and ALS patients. **Detailed Description:** Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant disease progression before formal diagnosis. Design: This is a phase I clinical trial and a 2-part, single center, open label study in healthy volunteers (Part A) and confirmed ALS patients (Part B). The primary goal is evaluating the safety and biodistribution of the radiotracer \[89Zr\]Zr-DFO-AP-101 in healthy volunteers and ALS patients via PET/CT imaging. Objectives: The primary objectives of this study are: (Part A) To evaluate, by PET imaging, the safety, biodistribution and dosimetry of \[89Zr\]Zr-DFO-AP-101 in healthy men and women and in ALS patients Intervention and Follow-up: Following a screening visit, eligible participants will come to the research center for all study assessments. * On Day 0, a single intravenous dose of \[89Zr\]Zr-DFO-AP-101 40 MBq will be administrated and a 45 min whole body PET/CT acquisition will be performed at two hours post injection. Physical exam, ECG, vital signs and blood/urine samples will be collected. * Further PET acquisitions and same data/samples collection will be repeated at days 1, 3, 7 and 10 post-injection. * Participants will be contacted for a final follow-up visit approximately 14 days after injection. ### Conditions Module **Conditions:** - Amyotrophic Lateral Sclerosis **Keywords:** - PET imaging - CT imaging - AP-101 - 89-Zirconium - DFO ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Two groups will be enrolled: 8 healthy subjects and 4 patients with ALS This is non-randomized, all participants will receive the same dose of radiotracer ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 12 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0. **Intervention Names:** - Drug: 89Zr-DFO-AP-101 **Label:** Healthy participants **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0. **Intervention Names:** - Drug: 89Zr-DFO-AP-101 **Label:** Patients with ALS **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy participants - Patients with ALS **Description:** At Day 0, patients will receive one dose of the radiotracer. A PET/CT scan will be done 2h post-dose. At 1, 3, 7 and 10 days post-dose, a PET/CT scan will be repeated. **Name:** 89Zr-DFO-AP-101 **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Assessment of target organ/tissue ratio in ALS patients versus healthy volunteers **Measure:** Differential labeling and uptake **Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose #### Primary Outcomes **Description:** Number of adverse events (AEs) and serious adverse events following administration of \[89Zr\]Zr-DFO-AP-101 that are new or worsened (compared to baseline/pre-dose) **Measure:** Incidence of adverse events (AEs) and serious adverse events (SAEs) **Time Frame:** day 0 (post-injection) to day 14 (end of study) **Description:** Assessed by whole-body PET imaging **Measure:** Biodistribution of [89Zr]Zr-DFO-AP-101 **Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose **Description:** Organ activity concentration (in liver, kidneys, blood, spleen, ...) measured by drawing region of interests on the PET images. **Measure:** Dosimetry of [89Zr]Zr-DFO-AP-101 in human **Time Frame:** Pre-Dose and at 2 hours, 1, 3, 7, 10 days post-dose #### Secondary Outcomes **Description:** Maximal concentration of \[89Zr\]Zr-DFO-AP-101 in plasma over time after injection **Measure:** Cmax **Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose **Description:** AUC of \[89Zr\]Zr-DFO-AP-101 in plasma over time after injection **Measure:** Area under the curve (AUC) **Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose **Description:** Time (1/2) of residence of \[89Zr\]Zr-DFO-AP-101 in plasma **Measure:** residence time **Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose **Description:** Concentration of \[89Zr\]Zr-DFO-AP-101 urine over time **Measure:** Excretion **Time Frame:** Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Aged of: 1. For healthy participants: Male or female subjects aged 50 years or older 2. For ALS patients: Male or female subjects aged 18 years and older 2. Able to remain in a lying position for up to 45 minutes without respiratory support. 3. A) For ALS patients, confirmed diagnostic of definitive ALS according to El-Escorial criteria14 B) for healthy participants: no neurologic condition (confirmed by physical exam) 4. Have venous access sufficient to allow for blood sampling 5. Are reliable and willing to make themselves available for the duration of the study and are willing to follow CRCHUS-specific study procedures. Exclusion Criteria: 1. Are currently enrolled or were enrolled in the last 12 weeks in any other clinical trial involving a study drug or off label use of a drug or device, or any other type of medical research judged not to be scientifically or medically compatible with this study. 2. Female participants who are pregnant or breast feeding; or women of childbearing potential (\<50 years old) and men who are sexually active who are not willing to use an accepted effective contraceptive method. 3. Plan to have surgery or other invasive procedure during the course of the study (up to 14 days post-injection) 4. Have a progressive medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality at screening and at first visit (D0) that, in the judgment of the medical doctor, indicate a medical problem that would preclude study participation. 5. Have one of these conditions (for both patient groups): 1. hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) and hematology abnormalities at screening. 2. severe chronic kidney disease (eg, an estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73m or requires chronic dialysis) at screening. 3. Have severe active psychiatric illness. 4. Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer's disease, etc). 5. Have a significant infection or known inflammatory process on screening or at Day 0. 6. Alcohol or drug abuse based on patient auto-report 7. Have a history of relevant atopy or drug hypersensitivity or allergy to antibodies; 8. Have an abnormal blood pressure (supine) defined as a diastolic blood pressure \>90 or \<45 mmHg and/or a systolic blood pressure \>160 or \<90 mmHg. Re-testing may occur once during the screening visit within 2 hours of the initial abnormal blood pressure measurement at the discretion of the investigator. 6. For ALS patients: 1. Have undergone a tracheostomy for ALS symptoms. 2. Are on nasal intermittent positive pressure ventilation (NIPPV) \>4h during the day, while awake for the treatment of ALS related symptoms. 3. Have other causes of neuromuscular weakness. 7. Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs and AP-101) within 3 months or 5 half-lives (whichever is longer) prior to study drug injection. 8. Have received any blood or blood products within the 3 months prior to screening. 9. Cannot communicate reliably with the investigator. 10. Are unwilling or unable to give written informed consent. 11. In the opinion of the medical doctor or his/her delegate, are unsuitable for inclusion in the study. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** amelie.tetu.ciussse-chus@ssss.gouv.qc.ca **Name:** Amelie Tetu, MSc **Phone:** 819-346-1110 **Role:** CONTACT **Contact 2:** **Email:** sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca **Name:** Sarah Côté-Bigras, MSc **Phone:** 819-346-1110 **Role:** CONTACT #### Locations **Location 1:** **City:** Sherbrooke **Contacts:** ***Contact 1:*** - **Email:** amelie.tetu.ciussse-chus@ssss.gouv.qc.ca - **Name:** Amelie Tetu - **Role:** CONTACT ***Contact 2:*** - **Email:** sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca - **Name:** Sarah Côté-Bigras - **Role:** CONTACT ***Contact 3:*** - **Name:** Brigitte Guérin, PhD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Eric E Turcotte, MD - **Role:** SUB_INVESTIGATOR **Country:** Canada **Facility:** CIUSSS de l'Estrie-CHUS Hospital **State:** Quebec **Status:** RECRUITING **Zip:** J1H 5N4 #### Overall Officials **Official 1:** **Affiliation:** Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke **Name:** Eric E Turcotte, MD **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke **Name:** Brigitte Guérin, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000057177 - Term: TDP-43 Proteinopathies - ID: D000057165 - Term: Proteostasis Deficiencies - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M18879 - Name: Motor Neuron Disease - Relevance: HIGH - As Found: Lateral Sclerosis - ID: M4024 - Name: Amyotrophic Lateral Sclerosis - Relevance: HIGH - As Found: Amyotrophic Lateral Sclerosis - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M28759 - Name: TDP-43 Proteinopathies - Relevance: LOW - As Found: Unknown - ID: M28747 - Name: Proteostasis Deficiencies - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: T349 - Name: Amyotrophic Lateral Sclerosis - Relevance: HIGH - As Found: Amyotrophic Lateral Sclerosis - ID: T4699 - Name: Primary Lateral Sclerosis - Relevance: HIGH - As Found: Lateral Sclerosis ### Condition Browse Module - Meshes - ID: D000016472 - Term: Motor Neuron Disease - ID: D000000690 - Term: Amyotrophic Lateral Sclerosis - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03839979 **Brief Title:** HCV Viral Hepatitis, Blood Sugar Level and Systolic Blood Pressure in Egypt **Official Title:** Association Between HCV Viral Hepatitis, Blood Sugar Level and Systolic Blood Pressure in the Egyptian Population #### Organization Study ID Info **ID:** One million healthy citizen 18 #### Organization **Class:** OTHER **Full Name:** Cairo University ### Status Module #### Completion Date **Date:** 2019-01-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-03-18 **Type:** ACTUAL **Last Update Submit Date:** 2021-03-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-12-31 **Type:** ACTUAL #### Start Date **Date:** 2018-10-01 **Type:** ACTUAL **Status Verified Date:** 2021-03 #### Study First Post Date **Date:** 2019-02-15 **Type:** ACTUAL **Study First Submit Date:** 2019-02-09 **Study First Submit QC Date:** 2019-02-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cairo University #### Responsible Party **Investigator Affiliation:** Cairo University **Investigator Full Name:** Mina Wageh Mohareb **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** An observational double-blind cohort study that examined the association between HCV viral hepatitis, blood sugar level and systolic blood pressure in the Egyptian population **Detailed Description:** a cohort study on greater than 70000 Egyptian patients had been conducted. for all patients,1- we detected the Hepatitis C Virus (HCV) RNA antigens ( hepatitis C virus)presence using BIOLINE HCV kits( qualitative test for diagnosis of hepatitis C virus in the blood), For all positive patients, confirmatory rapid screening test was performed and all patients who tested positive twice underwent a qPCR test using QIAampMinElute Virus Spin kit (Thermo Fisher Scientific, Waltham, MA, USA) performed according to the manufacturer's recommended protocol. 2- Investigators measured blood sugar levels for each patient using ACCU-CHEK kits(finger stick sugar level measurement) 3- Measured systolic blood pressure for each patient was measured using mercury meters. 4-for all patients investigators obtained full medical history regarding the presence or absence of chronic diabetes, chronic hypertension, coronary artery disease, kidney impairment with dialysis or chronic obstructive pulmonary disease. 5- for all patients investigators listed age, gender, and body mass index. 66121 patients were negative for HCV and 4852 were positive for HCV. Investigators measured the association between HCV presence, high blood sugar levels and high systolic blood pressure. It is supposed that this is the largest study in the world that examined both associations. In a word, this study was responding to a specific question: is hepatitis c virus presence is associated with high blood pressure or high sugar level or both or not associated??? ### Conditions Module **Conditions:** - Hepatitis C, Acute - Diabetes - Hypertension ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 71975 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients tested positive for the hepatitis c virus antibodies by BIOLINE HCV kits. **Intervention Names:** - Diagnostic Test: BIOLINE HCV kits - Diagnostic Test: ACCU-CHEK kits - Diagnostic Test: ErKameter 3000 mercury manometer **Label:** HCV positive patients #### Arm Group 2 **Description:** Patients tested negative for the hepatitis c virus antibodies by BIOLINE HCV kits. **Intervention Names:** - Diagnostic Test: BIOLINE HCV kits - Diagnostic Test: ACCU-CHEK kits - Diagnostic Test: ErKameter 3000 mercury manometer **Label:** HCV negative patients ### Interventions #### Intervention 1 **Arm Group Labels:** - HCV negative patients - HCV positive patients **Description:** We used BIOLINE HCV kits to detect the presence of HCV antibodies in stick blood samples of all recruited patients. **Name:** BIOLINE HCV kits **Other Names:** - diagnosis of viral hepatitis C **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - HCV negative patients - HCV positive patients **Description:** For all patients, we measured random blood sugar levels by stick blood samples using ACCU-CHEK kits. **Name:** ACCU-CHEK kits **Other Names:** - measurement of blood sugar level **Type:** DIAGNOSTIC_TEST #### Intervention 3 **Arm Group Labels:** - HCV negative patients - HCV positive patients **Description:** For all patients, we measured systolic blood pressure using ErKameter 3000 mercury manometer. **Name:** ErKameter 3000 mercury manometer **Other Names:** - blood pressure measurement **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Detection of patients who are HCV positive or negative **Measure:** HCV diagnosis **Time Frame:** 20 minutes **Description:** Detection of the percentage of patients with high blood sugar level in HCV positive or negative patients **Measure:** Measurement of blood sugar level in mg/dl **Time Frame:** 1 minute **Description:** Detection of the percentage of patients with high systolic blood pressure in HCV positive or negative patients **Measure:** Measurement of systolic blood pressure in mmHg **Time Frame:** 1 minute ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria * Egyptian citizens from 18 years to 80 years. Exclusion Criteria: * Patients younger than 18 years or older than 80 years **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Egyptian patients aged 18-80 years. ### Contacts Locations Module #### Locations **Location 1:** **City:** Asyut **Country:** Egypt **Facility:** Egyptian Ministry of Health **Zip:** 01234567 ### IPD Sharing Statement Module **Description:** No individual data will be shared with other researchers. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections - ID: D000004769 - Term: Enterovirus Infections - ID: D000010850 - Term: Picornaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000018178 - Term: Flaviviridae Infections ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M27583 - Name: Systolic Murmurs - Relevance: LOW - As Found: Unknown - ID: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M7930 - Name: Enterovirus Infections - Relevance: LOW - As Found: Unknown - ID: M13745 - Name: Picornaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000006505 - Term: Hepatitis ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M20971 - Name: Hepatitis C Antibodies - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01650779 **Brief Title:** A Study Evaluating Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta **Official Title:** Evaluation of Glycosphingolipid Clearance in Patients Treated With Agalsidase Alfa Who Switch to Agalsidase Beta (The INFORM Study) #### Organization Study ID Info **ID:** AGAL19412 #### Organization **Class:** INDUSTRY **Full Name:** Sanofi ### Status Module #### Completion Date **Date:** 2013-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-07-10 **Type:** ESTIMATED **Last Update Submit Date:** 2014-06-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-07-10 **Type:** ESTIMATED **Results First Submit Date:** 2014-06-09 **Results First Submit QC Date:** 2014-06-09 #### Start Date **Date:** 2012-04 **Status Verified Date:** 2014-06 #### Study First Post Date **Date:** 2012-07-26 **Type:** ESTIMATED **Study First Submit Date:** 2012-07-24 **Study First Submit QC Date:** 2012-07-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Genzyme, a Sanofi Company #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an exploratory study to evaluate changes in glycosphingolipid levels and other (exploratory) Fabry disease parameters in male Fabry disease participants who were previously treated with agalsidase alfa (Replagal®) 0.2 milligram per kilogram (mg/kg) every two weeks (q2w) and who are being switched to agalsidase beta (Fabrazyme®) 1.0 mg/kg q2w. ### Conditions Module **Conditions:** - Fabry Disease **Keywords:** - alpha-galactosidase A - a-GAL - Fabry - GL-3 - Fabrazyme ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 15 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: Agalsidase beta **Label:** Agalsidase beta **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Agalsidase beta **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. **Name:** Agalsidase beta **Other Names:** - Fabrazyme® **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Percent change from baseline = (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. For levels reported as below quantitative limit (BQL), the lower limit of quantitation (LLOQ) value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma lyso-GL-3 was 5.0 nanogram per milliliter (ng/mL). This study is exploratory because little is known about the dose-response of these biomarkers to enzyme replacement therapy (ERT) or about the clinical significance of the biomarkers. **Measure:** Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6 **Time Frame:** Baseline, Month 2, 4, 6 #### Secondary Outcomes **Description:** Percent change from baseline = (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma GL-3 was 2.0 microgram per milliliter (mcg/mL). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. **Measure:** Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6 **Time Frame:** Baseline, Month 2, 4, 6 **Description:** Percent change from baseline = (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for urine GL-3 was 0.2 mcg/mL. The absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing GL-3 (mcg/mL) by creatinine (mg/mL) and multiplying by 113.13 (mg/mmol), the molecular weight of creatinine. For levels reported BQL, the absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing 0.1 (mcg/mL) by creatinine (mg/mL) and multiplying by 133.13 (mg/mmol). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. **Measure:** Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6 **Time Frame:** Baseline, Month 2, 4, 6 **Description:** Gastrointestinal symptoms (abdominal pain, abdominal distention, and irregular bowel movements) were to be assessed by a modified version of the Irritable Bowel Syndrome (IBS) Severity Scoring System. The modified IBS Severity Scoring System is a 7-item questionnaire. The severity score calculated by summing the scores of 5 of the 7 questions. Each of the 5 questions were scored on a scale of 0 to 100, leading to a total possible score range of 0 to 500, where higher scores indicate more severe gastrointestinal symptoms. The data for this outcome measure was exploratory and to be collected in individual participant listing only. **Measure:** Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6 **Time Frame:** Baseline, Month 2, 4, 6 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * The participant and/or his parent/legal guardian is willing and able to provide signed informed consent, and the participant, if less than (\<) 18 years of age, is willing to provide assent if deemed able to do so * Participant is male and has been treated with agalsidase alfa at 0.2 mg/kg q2w for the 12 months prior to switching to agalsidase beta * The participant has a confirmed diagnosis of Fabry disease by alfa-galactosidase A (alfa-GAL) activity and/or genotyping per local standards * The participant when switched to agalsidase beta receives the labeled dose, that is, 0.9 to 1.1 mg/kg (1 mg/kg) q2w, and must be willing to maintain the labeled dose for the duration of the study Exclusion Criteria: * The participant is on dialysis or is post renal transplantation * The participant is in end-stage cardiac failure * The participant and/or his parent or legal guardian, in the opinion of the investigator, is unable to adhere to the requirements of the study * The participant has been switched from agalsidase alfa to agalsidase beta and does not have historical blood and urine samples **Sex:** MALE **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Coral Springs **Country:** United States **State:** Florida **Location 2:** **City:** Decatur **Country:** United States **State:** Georgia **Location 3:** **City:** Baltimore **Country:** United States **State:** Maryland **Location 4:** **City:** Grand Rapids **Country:** United States **State:** Michigan **Location 5:** **City:** Hellertown **Country:** United States **State:** Pennsylvania **Location 6:** **City:** Fairfax **Country:** United States **State:** Virginia #### Overall Officials **Official 1:** **Affiliation:** Genzyme, a Sanofi Company **Name:** Medical Monitor **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013106 - Term: Sphingolipidoses - ID: D000020140 - Term: Lysosomal Storage Diseases, Nervous System - ID: D000020739 - Term: Brain Diseases, Metabolic, Inborn - ID: D000001928 - Term: Brain Diseases, Metabolic - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000059345 - Term: Cerebral Small Vessel Diseases - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000040181 - Term: Genetic Diseases, X-Linked - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000008661 - Term: Metabolism, Inborn Errors - ID: D000008064 - Term: Lipidoses - ID: D000008052 - Term: Lipid Metabolism, Inborn Errors - ID: D000016464 - Term: Lysosomal Storage Diseases - ID: D000008659 - Term: Metabolic Diseases - ID: D000052439 - Term: Lipid Metabolism Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4124 - Name: Fabry Disease - Relevance: HIGH - As Found: Fabry Disease - ID: M15904 - Name: Sphingolipidoses - Relevance: LOW - As Found: Unknown - ID: M18871 - Name: Lysosomal Storage Diseases - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5205 - Name: Brain Diseases, Metabolic - Relevance: LOW - As Found: Unknown - ID: M22498 - Name: Brain Diseases, Metabolic, Inborn - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M29437 - Name: Cerebral Small Vessel Diseases - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M24877 - Name: Genetic Diseases, X-Linked - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M11641 - Name: Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M11064 - Name: Lipidoses - Relevance: LOW - As Found: Unknown - ID: M11054 - Name: Lipid Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: T2169 - Name: Fabry Disease - Relevance: HIGH - As Found: Fabry Disease - ID: T5335 - Name: Sphingolipidosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000795 - Term: Fabry Disease ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** All enrolled participants were included in the analysis. #### Event Groups **Group ID:** EG000 **Title:** Agalsidase Beta **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion every 2 weeks up to Month 6. **ID:** EG000 **Other Num Affected:** 1 **Other Num at Risk:** 15 **Serious Number At Risk:** 15 **Title:** Agalsidase Beta **Frequency Threshold:** 0 #### Other Events **Term:** Infusion-associated reactions **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 16.0 **Time Frame:** Baseline up to end of study (Month 6) or early withdrawal ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 15 **Units:** Participants ### Group **ID:** BG000 **Title:** Agalsidase Beta **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 16.11 **Value:** 28.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 15 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Class Title:** Caucasian #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Hispanic #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Other ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 2 **Spread:** 4.73 **Upper Limit:** 19 **Value:** 9.3 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 14 **Class Title:** Genotype #### Measurement **Group ID:** BG000 **Value:** 11 **Class Title:** Leukocyte alfa-galactosidase A (GAL) activity #### Measurement **Group ID:** BG000 **Value:** 9 **Class Title:** Plasma alfa-GAL activity **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** participants ### Measure 4 **Description:** Duration of Fabry disease was calculated from date of initial diagnosis of Fabry disease to date of the first study infusion. Number of participants analyzed for this baseline measure were 14, as one participant did not have information on date of initial diagnosis of Fabry disease. **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Title:** Duration of Fabry Disease **Unit of Measure:** years ### Measure 5 **Description:** Number of participants with each method (genotype, leukocyte alfa-galactosidase A \[GAL\] activity, and plasma alfa-GAL activity) are reported. Some participants were diagnosed by more than 1 method, hence reported under more than 1 category. **Parameter Type:** NUMBER **Title:** Method of Diagnosis of Fabry Disease **Unit of Measure:** participants **Population Description:** All enrolled participants were included in the analysis. ## Results Section - More Information Module ### Certain Agreement **Other Details:** If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Limitations and Caveats **Description:** This is considered to be an exploratory study for the following reasons: it was based on a small number of participants and has been designed as an open-label, single-arm study as opposed to a two-arm crossover design. ### Point of Contact **Email:** Contact-us@sanofi.com **Organization:** Sanofi **Title:** Trial Transparency Team ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 2: Analysis was performed using one sample t-test. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample t-test **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 4: Analysis was performed using one sample t-test. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample t-test **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 6: Analysis was performed using one sample t-test. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample t-test **Tested Non-Inferiority:** False ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 2: Analysis was performed using one sample t-test. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1178 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample t-test **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 4: Analysis was performed using one sample t-test. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1176 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample t-test **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 6: Analysis was performed using one sample t-test. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0322 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample t-test **Tested Non-Inferiority:** False ### Outcome Measure 3 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 2: Analysis was performed using one sample test of median (sign test). The percent change and absolute change from baseline in urine GL-3 levels were not normally distributed and thus medians were evaluated. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5811 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample test of median (sign test) **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 4: Analysis was performed using one sample test of median (sign test). The percent change and absolute change from baseline in urine GL-3 levels were not normally distributed and thus medians were evaluated. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.7744 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample test of median (sign test) **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline versus Month 6: Analysis was performed using one sample test of median (sign test). The percent change and absolute change from baseline in urine GL-3 levels were not normally distributed and thus medians were evaluated. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3877 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** One sample test of median (sign test) **Tested Non-Inferiority:** False ### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22.540 - **Upper Limit:** - **Value:** -31.71 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22.280 - **Upper Limit:** - **Value:** -39.04 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.567 - **Upper Limit:** - **Value:** -39.54 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 21.087 - **Upper Limit:** - **Value:** -10.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.388 - **Upper Limit:** - **Value:** -12.80 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 25.291 - **Upper Limit:** - **Value:** -17.89 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -98.4 - **Spread:** - **Upper Limit:** 1068.2 - **Value:** -44.71 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -96.5 - **Spread:** - **Upper Limit:** 464.9 - **Value:** -41.49 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -97.1 - **Spread:** - **Upper Limit:** 1116.7 - **Value:** -33.75 **Title:** #### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Percent change from baseline = (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. For levels reported as below quantitative limit (BQL), the lower limit of quantitation (LLOQ) value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma lyso-GL-3 was 5.0 nanogram per milliliter (ng/mL). This study is exploratory because little is known about the dose-response of these biomarkers to enzyme replacement therapy (ERT) or about the clinical significance of the biomarkers. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All enrolled participants were included in the analysis. Here, 'n' signifies participants with plasma Lyso-GL-3 assessment at the specified time point. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 2, 4, 6 **Title:** Percent Change From Baseline in Plasma Deacylated Globotriaosylceramide (Lyso-GL-3) at Month 2, 4 and 6 **Type:** PRIMARY **Unit of Measure:** percent change ##### Group **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. **ID:** OG000 **Title:** Agalsidase Beta #### Outcome Measure 2 **Description:** Percent change from baseline = (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for plasma GL-3 was 2.0 microgram per milliliter (mcg/mL). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All enrolled participants were included in the analysis. Here, 'n' signifies participants with plasma GL-3 assessment at the specified time point. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 2, 4, 6 **Title:** Percent Change From Baseline in Plasma Globotriaosylceramide (GL-3) at Month 2, 4 and 6 **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. **ID:** OG000 **Title:** Agalsidase Beta #### Outcome Measure 3 **Description:** Percent change from baseline = (\[post-baseline value minus baseline value\] divided by \[baseline value\]) multiplied by 100. For levels reported as BQL, the LLOQ value was divided by 2 and used in the calculation to estimate values in samples that were BQL. The LLOQ for urine GL-3 was 0.2 mcg/mL. The absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing GL-3 (mcg/mL) by creatinine (mg/mL) and multiplying by 113.13 (mg/mmol), the molecular weight of creatinine. For levels reported BQL, the absolute values were calculated in microgram per millimole (mcg/mmol) of creatinine by dividing 0.1 (mcg/mL) by creatinine (mg/mL) and multiplying by 133.13 (mg/mmol). This study is exploratory because little is known about the dose-response of these biomarkers to ERT or about the clinical significance of the biomarkers. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** All enrolled participants were included in the analysis. Here, 'n' signifies participants with urine GL-3 assessment at the specified time point. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 2, 4, 6 **Title:** Percent Change From Baseline in Urine GL-3 at Month 2, 4, and 6 **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. **ID:** OG000 **Title:** Agalsidase Beta #### Outcome Measure 4 **Description:** Gastrointestinal symptoms (abdominal pain, abdominal distention, and irregular bowel movements) were to be assessed by a modified version of the Irritable Bowel Syndrome (IBS) Severity Scoring System. The modified IBS Severity Scoring System is a 7-item questionnaire. The severity score calculated by summing the scores of 5 of the 7 questions. Each of the 5 questions were scored on a scale of 0 to 100, leading to a total possible score range of 0 to 500, where higher scores indicate more severe gastrointestinal symptoms. The data for this outcome measure was exploratory and to be collected in individual participant listing only. **Population Description:** The data for this outcome measure was exploratory and to be collected in individual participant listing only. Analysis of this data was planned only if baseline data was collected on a large number of enrolled participants. This was not the case and therefore interpretation of these results were not possible. **Reporting Status:** POSTED **Time Frame:** Baseline, Month 2, 4, 6 **Title:** Percent Change From Baseline in Gastrointestinal (GI) Symptoms (Abdominal Pain, Abdominal Distention, and Bowel Irregularities) at Month 2, 4, and 6 **Type:** SECONDARY ##### Group **Description:** Commercially available agalsidase beta 1.0 mg/kg administered as an intravenous infusion q2w up to Month 6. **ID:** OG000 **Title:** Agalsidase Beta ### Participant Flow Module #### Group **Description:** Commercially available agalsidase beta (Fabrazyme ®) 1.0 milligram per kilogram (mg/kg) administered as an intravenous infusion every 2 weeks (q2w) up to Month 6. **ID:** FG000 **Title:** Agalsidase Beta #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 15 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 **Pre-Assignment Details:** A total of 16 participants were screened of which 1 participant was screen failure. A total of 15 participants were enrolled in this study. **Recruitment Details:** The study was conducted at 6 centers in the United States of America between April 30, 2012 and March 15, 2013. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01111279 **Brief Title:** Clinical Safety and Tolerability Study of gpASIT+TM and gpASIT+TM/Immunoregulating Adjuvant to Treat Seasonal Grass Pollen Rhinoconjunctivitis **Official Title:** Clinical Safety and Tolerability of gpASIT+TM Administered Subcutaneously in Absence or in Presence of DnaK Immunoregulating Adjuvant for the Prophylaxis of Seasonal Grass Pollen Rhinoconjunctivitis #### Organization Study ID Info **ID:** BTT-gpASIT004 #### Organization **Class:** INDUSTRY **Full Name:** BioTech Tools S.A. ### Status Module #### Completion Date **Date:** 2010-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2011-03-01 **Type:** ESTIMATED **Last Update Submit Date:** 2011-02-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-09 **Type:** ACTUAL #### Start Date **Date:** 2010-03 **Status Verified Date:** 2011-02 #### Study First Post Date **Date:** 2010-04-27 **Type:** ESTIMATED **Study First Submit Date:** 2010-04-20 **Study First Submit QC Date:** 2010-04-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** BioTech Tools S.A. #### Responsible Party **Old Name Title:** Thierry Legon / CEO **Old Organization:** BioTech Tools ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to assess the safety and tolerability of gpASIT+TM administered subcutaneously in absence or in presence of an immunoregulating adjuvant in grass pollen allergic patients. ### Conditions Module **Conditions:** - Seasonal Allergic Rhinoconjunctivitis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 27 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: Placebo solution **Label:** Placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Intervention Names:** - Biological: gpASIT+TM **Label:** gpASIT+TM **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Biological: gpAST+TM/adjuvant **Label:** gpASIT+TM/adjuvant **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - gpASIT+TM **Description:** 1 subcutaneous injection every 7 days, during 29 days. **Name:** gpASIT+TM **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - gpASIT+TM/adjuvant **Description:** 1 subcutaneous injection every 7 days, during 29 days **Name:** gpAST+TM/adjuvant **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - Placebo **Description:** 1 subcutaneous injection every 7 days, during 29 days **Name:** Placebo solution **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** The following parameters will be assessed : general physical status, vital signs, haematological parameters , general blood biochemistry parameters, all (serious) adverse, immunological analysis (total IgG, total IgE) and inflammatory parameters (CRP, sedimentation rate) **Measure:** Clinical tolerability and safety of the treatment **Time Frame:** 3 times during the treatment phase, at week 24 (the end of the study) #### Secondary Outcomes **Description:** The following parameters will be assessed : * allergen-specific IgE, IgG, IgG4, IgA antibody concentrations, * adjuvant-specific IgG antibody concentrations, * lymphoproliferation and production of IL-10 in allergen and adjuvant stimulated PBMC. **Measure:** Impact of gpASIT+TM on the immunological status of the subjects **Time Frame:** visit 1, week 7, week 18 and week 24 **Description:** The following parameters will be assessed (during the pollen season following treatment): * daily average allergic symptom score, * daily average allergic medication score, * number of "well-days", * Visual Analogue Scale . **Measure:** Impact of gpASIT+TM on the clinical status of the subjects **Time Frame:** 1 May - 15 August 2010 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject has given written informed consent * Age between 18 and 50 years * The subjects are in good physical and mental health according to his/her medical history, vital signs, and clinical status * Male or non pregnant, non-lactating female * Females unable to bear children must have documentation of such in the CRF (i.e. tubule ligation, hysterectomy, or post menopausal (defined as a minimum of one year since the last menstrual period)) * Allergy diagnosis: * A history of seasonal allergic rhinoconjunctivitis (SAR) during the grass pollen season during at least during the two previous years * A positive skin prick test (wheal diameter ≥ 3 mm) to grass-pollen mixture * Specific IgE against grass pollen (RAST class 2 or IgE \> 0.7 kU/l) * Asymptomatic to perennial inhalant allergens even if shown to be hypersensitive in a skin prick test. Exclusion Criteria: * Subjects with current or past immunotherapy (any time in the past) * A history of hypersensitivity to the excipients * Subjects requiring control medication against asthma (bronchodilator nebulised drugs or local or systemic corticosteroids) * Subjects with documented evidence of acute or significant chronic sinusitis (as determined by investigator) * Subjects with a history of hepatic or renal disease * Subjects symptomatic to perennial inhalant allergens * Subjects with rhinitis medicamentosa, non-specific rhinitis (to food dye, preservative agent...) * Subject with malignant disease, autoimmune disease (and family medical history of autoimmune disease) * Any chronic disease, which may impair the subject's ability to participate in the trial (i.e. severe congestive heart failure, active gastric or duodenal ulcer, uncontrolled diabetes mellitus, etc...) * Subjects requiring beta-blockers medication * Chronic use of concomitant medications that would affect assessment of the effectiveness of the trial medication (e.g. tricyclic antidepressants) * Subject with febrile illness (\> 37.5°C, oral) * A known positive serology for HIV-1/2, HBs antigen or anti-HCV antibodies * The subject is immunocompromised by medication or illness, has received a vaccine, corticoids or immunosuppressive medications within 1 month before trial entry * Receipt of blood or a blood derivative in the past 6 months preceding trial entry * Regular consumption of corticoids (oral, topic or nasal) or of anti-histaminic drugs within 4 weeks preceding the trial * Any consumption of corticoids (oral, topic or nasal) or of anti-histaminic drugs within 1 week preceding the trial * Use of long-acting antihistamines * Female subjects who are pregnant, lactating, or of child-bearing potential and not protected from pregnancy by a sufficiently reliable method (OCs, IUD) * Any condition which could be incompatible with protocol understanding and compliance * Subjects who have forfeited their freedom by administrative or legal award or who are under guardianship * Unreliable subjects including non-compliant subjects, subjects with known alcoholism or drug abuse or with a history of a serious psychiatric disorder as well as subjects unwilling to give informed consent or to abide by the requirements of the protocol * Subjects without means of contacting the investigator rapidly in case of emergency, or not able to be contacted rapidly by the investigator * Participation in another clinical trial and/or treatment with an experimental drug within 1 month of trial start * Subjects who participated to trial BTT-gpASIT003 and were in the treated groups **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Leuven **Country:** Belgium **Facility:** UZ Leuven, Gasthuisberg **Zip:** 3000 #### Overall Officials **Official 1:** **Affiliation:** UZ Leuven **Name:** Jan Ceuppens, Professor **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003229 - Term: Conjunctival Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M6455 - Name: Conjunctivitis - Relevance: HIGH - As Found: Rhinoconjunctivitis - ID: M6453 - Name: Conjunctival Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003231 - Term: Conjunctivitis ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05930379 **Brief Title:** A Feasibility Pilot Study on Lee Silverman Voice Treatment-Loud: a Telerehabilitation Approach **Official Title:** A Feasibility Pilot Study on Lee Silverman Voice Treatment (LSVT)-Loud on Voice Intensity and Voice Use in Daily Living in People With Multiple Sclerosis: a Telerehabilitation Approach #### Organization Study ID Info **ID:** ON-LOUD #### Organization **Class:** OTHER **Full Name:** Fondazione Don Carlo Gnocchi Onlus ### Status Module #### Completion Date **Date:** 2024-07-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-06 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-04 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2023-06-10 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2023-07-05 **Type:** ACTUAL **Study First Submit Date:** 2023-06-26 **Study First Submit QC Date:** 2023-06-26 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Fondazione Italiana Sclerosi Multipla #### Lead Sponsor **Class:** OTHER **Name:** Fondazione Don Carlo Gnocchi Onlus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Multiple Sclerosis (MS) is one of the most common causes of neurological disability in young adults. At least 62% of people with MS have speech, vocal, or communication disorders. Among these, alterations in voice intensity and quality constitute a limitation in MS people's social life leading to experience difficulties in work, conversations, and communication especially in noisy environments or through the telephone. Though voice and speech impairments and speech impairments are widely prevalent in this population, only 2% of the people receive speech therapy. The Lee Silverman Voice Treatment (LSVT)-Loud is a well-documented, efficacious intensive speech intervention, for treating hypophonia in subjects with neurological conditions. Despite the effectiveness of LSVT-Loud treatment on the voice has been reported in MS, several factors prevent the agile use of this method in rehabilitation centers: motor disability, work commitments, and distance barriers may preclude repeated attendance of this intervention at a healthcare facility. Telerehabilitation represents a feasible solution to bypass these potential barriers related to attendance at the rehabilitation programs in the clinic. The increasing evidence sustains the role of telerehabilitation for the migration of care from the clinic to the patient's homes, overcoming several obstacles affecting service accessibility. Previous studies showed the validity and the non-inferiority of LSVT-Loud delivered via telerehabilitation in subjects with Parkinson's Disease, while no pieces of evidence are still available on the efficacy of voice treatment delivered by telerehabilitation in MS. It is plausible to assume that LSVT-Loud delivered by telerehabilitation would be feasible and provide a beneficial effect also for MS non-inferior compared to the same treatment delivered in the clinic. **Detailed Description:** 20 patients with MS will be recruited from IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, according to inclusion/exclusion criteria detailed in the "Eligibility Criteria" section. Participants will be randomized into 2 different groups: Group 1: Lee Silverman Voice Treatment - Loud delivered by telerehabilitation at home (Experimental group); Group 2: Lee Silverman Voice Treatment - Loud delivered in the clinic (Control group). ### Conditions Module **Conditions:** - Multiple Sclerosis **Keywords:** - Telerehabilitation - Speech Therapy - Multiple Sclerosis - Voice Intensity - Hypophonia - Digital Health ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** F - Frequency: 7 times/week for 4 weeks according to a mixed model (4 days of synchronous sessions followed by independent practice + 3 asynchronous sessions); I - Intensity: sessions customized according to the patient's functional abilities to ensure the progression of difficulty in rehabilitation sessions; T- Time: each synchronous session will last about 60 minutes, each independent practice will last about 5-10 minutes, and each asynchronous session will last about 30 minutes; T- Type: Individual speech therapy sessions with the Lee Silverman Voice Treatment-Loud method delivered by telerehabilitation. **Intervention Names:** - Other: LSVT-Loud delivered by telerehabilitation **Label:** LSVT-Loud delivered by telerehabilitation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The frequency, intensity, time of the rehabilitation sessions will be the same as the experimental group. T- Type: Individual speech therapy sessions with the Lee Silverman Voice Treatment-Loud method delivered in the clinic. **Intervention Names:** - Other: LSVT-Loud in the clinic **Label:** LSVT-Loud in the clinic **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - LSVT-Loud delivered by telerehabilitation **Description:** LSVT-Loud treatment delivered by telerehabilitation **Name:** LSVT-Loud delivered by telerehabilitation **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - LSVT-Loud in the clinic **Description:** LSVT-Loud delivered face-to-face in the clinic **Name:** LSVT-Loud in the clinic **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** The UEQ is a 26-item scale (semantic differential scale: each item consists of two opposite adjectives, e.g., boring vs. exciting) that allows calculating six different domains: (1) attractiveness (overall impression of the system), (2) perspicuity: easily to learn how to use the system; (3) efficiency (user's effort to solve tasks); (4) dependability (feeling of control of the interaction); (5) stimulation (motivation to use the system); and (6) novelty (innovation and creation of system). The mean of the item score of each domain will be standardized based on a data benchmark (Schrepp et al., 2017). **Measure:** Technological Systems interaction perceived experience as measured by the User Experience Questionnaire (UEQ; Schrepp et al., 2017) **Time Frame:** post-treatment (up to 4 weeks) **Description:** IMI-IE consisted of a pool of 7 items with a 7 points Likert scale ranging from (1) "Absolutely Not" to (7) "Absolutely Yes". A total score (average of the item scores) will be considered. **Measure:** Intrinsic Motivation in the rehabilitation program as measured by the Intrinsic Motivation Inventory - Interest/Enjoyment subscale (IMI-IE; McAuley et al., 1989) **Time Frame:** post-treatment (up to 4 weeks) **Description:** Adverse events will be listed in the patient's diary considering both events occurring during the therapy and those occurring outside of the sessions but within the rehabilitation protocol period **Measure:** Number of adverse events **Time Frame:** post-treatment (up to 4 weeks) **Description:** Individual and group ad-hoc interviews will be performed during and after the rehabilitation protocol period. **Measure:** 4. Perceived rehabilitation engagement, acceptability, feasibility, frequency, and dose adequacy **Time Frame:** post-treatment (up to 4 weeks) #### Primary Outcomes **Description:** Participants will be requested to speak about daily activities at a comfortable frequency and intensity level. A specific task identical for each participant will be given: "Please speak for at least a minute." For monologue (and other acoustic variables described below) recording setup follows published recommendations, mouth-to-microphone distance is kept at 30 cm and we will calculate the mean of the first three recordings and PRAAT software (www.praat.org) will be used to record and analyze voice parameters. **Measure:** Change in the vocal Intensity during 1-minute monologue dB SPL **Time Frame:** Baseline, post-treatment (up to 4 weeks) #### Secondary Outcomes **Description:** Participants will be requested to speak about daily activities at a comfortable frequency and intensity level. A specific task identical for each participant will be given: "Please speak for at least a minute." For monologue (and other acoustic variables described below) recording setup follows published recommendations, mouth-to-microphone distance is kept at 30 cm and we will calculate the mean of the first three recordings and PRAAT software (www.praat.org) will be used to record and analyze voice parameters. **Measure:** Change in the vocal Intensity during 1-minute monologue dB SPL **Time Frame:** follow-up (up to 6 months from the end of the treatment) **Description:** Participants' voices will be monitored for a total of 4 hours of consecutive speech. Voice data from daily life will be registered using the Vocal Holter Med (VHM) before and after the interventions. VHM consists of a contact microphone placed in a collar worn around the neck as well as a device for data storage that can be worn in a pocket during the day. The contact microphone measures the skin vibrations caused by the activity of the vocal cords. Besides the voice indicators, also local temperature and relative humidity are measured during monitoring. **Measure:** Change in sustained /a/ voice intensity (dB SPL/a/) **Time Frame:** Baseline, post-treatment (up to 4 weeks) and follow-up (up to 6 months from the end of treatment) **Description:** VHI is a standardized 30-point questionnaire, divided into three subscales covering functional, emotional, and physical aspects of voice disorders. Participants have to rate each statement using a 5-point scale scored from 0 (never) to 4 (always); the maximum score is 120 (worst score). The value of 12 points on the VHI test should be considered as a threshold for rating the handicap caused by voice disorders. **Measure:** Change in the perception of voice as measured by the Voice Handicap Index (VHI, Jacobson et al., 1997) **Time Frame:** Baseline, post-treatment (up to 4 weeks) and follow-up (up to 6 months from the end of treatment **Description:** WHODAS 2.0 covers six domains of functioning including Cognition, Mobility, Self-care, Getting along, Life activities, Participation. Scores assigned to each item are on a 5-point scale ranging from (0) "none" to (4) "extreme" with higher scores indicating a higher disability. The 36-item version will be administered and both summary scores (score range 0-144 with higher numbers indicating higher disability) and domain-specific scores for the six different functioning domains (especially in cognition, life activities, and participation domain; score range 0-24 for each domain with higher numbers indicating higher disability) will be considered. **Measure:** hange in perceived quality of life (especially in cognition, life activities, and participation domain) as measured by the World Health Organization disability assessment schedule 2.0 (WHODAS 2.0; Federici et al., 2017) **Time Frame:** Baseline, post-treatment (up to 4 weeks) and follow-up (up to 6 months from the end of treatment **Description:** Synchronous sessions' adherence to the treatment will be registered by the telerehabilitation platform (experimental group) or by the therapist (control group). Asynchronous sessions' attendance will be registered by the completion of the patient's diary. **Measure:** Protocol adherence **Time Frame:** post-treatment (up to 4 weeks) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * diagnosis of MS according to the criteria of MC Donald 2010 (Polman et al., 2011; Thompson et al., 2018) * perceived voice intensity disability and severity of speech and voice disorder prior to treatment (as judged independently by two speech-language pathologists highly experienced with voice and motor speech disorders) * age ≥ 18; * not treated for hypophonia in the six months before enrollment in the study * with a preserved cognitive level at the Mini-Mental State Examination (MMSE test \>24) (Folstein et al., 1975); * available and able to use a PC with an internet connection at home to access the telerehabilitation sessions; * agreeing to participate with the signature of the informed consent form; * stable drug treatment (last 3 months), if any; * absence of relapses (last month) before taking part in the study. Exclusion Criteria: * presence of dysphonia related to other diseases; * presence of other neurological disorders different from MS; * presence of major psychiatric conditions; * presence of severe impairment of visual and/or acoustic perception; * history of laryngeal cancer, radiotherapy, or head-neck trauma, or intubation. **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** sisernia@dongnocchi.it **Name:** Sara Isernia, Ph.D. **Phone:** 00390240308952 **Role:** CONTACT #### Locations **Location 1:** **City:** Milan **Contacts:** ***Contact 1:*** - **Email:** sisernia@dongnocchi.it - **Name:** Sara Isernia, Ph.D. - **Phone:** 0240308952 - **Role:** CONTACT **Country:** Italy **Facility:** Fondazione Don Gnocchi ONLUS **State:** Italy/Milan **Status:** RECRUITING **Zip:** 20148 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M6374 - Name: Communication Disorders - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02135679 **Brief Title:** The Detection Of Circulating Tumor Cells (CTC) In Patients With NSCLC Undergoing Definitive Radiotherapy Or Chemoradiotherapy **Official Title:** The Detection Of Circulating Tumor Cells (CTC) In Patients With Non-small Cell Lung Cancer (NSCLC) Undergoing Definitive Radiotherapy Or Chemoradiotherapy #### Organization Study ID Info **ID:** UPCC 12512 #### Organization **Class:** OTHER **Full Name:** Abramson Cancer Center at Penn Medicine ### Status Module #### Completion Date **Date:** 2023-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-01 **Type:** ACTUAL **Last Update Submit Date:** 2023-02-28 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2019-12 **Type:** ACTUAL #### Start Date **Date:** 2012-09 **Status Verified Date:** 2023-02 #### Study First Post Date **Date:** 2014-05-12 **Type:** ESTIMATED **Study First Submit Date:** 2014-05-02 **Study First Submit QC Date:** 2014-05-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Abramson Cancer Center at Penn Medicine #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** CTC levels collected pre-surgery will be correlated with pathological samples. **Detailed Description:** Patients with NSCLC who undergo radiation as part of a definitive course of treatment will be enrolled. Blood collections will be obtained before, during, and after radiotherapy. We will collect demographic and treatment data and explore \& describe the pattern of CTC detection in all patients ### Conditions Module **Conditions:** - Non-small Cell Lung Cancer ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 153 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with early stage NSCLC undergoing stereotactic radiotherapy **Intervention Names:** - Radiation: Radiotherapy **Label:** Cohort 1 #### Arm Group 2 **Description:** Patients with locally advanced NSCLC undergoing standard chemoradiotherapy **Intervention Names:** - Radiation: Radiotherapy **Label:** Cohort 2 #### Arm Group 3 **Description:** Patients with stage I-III NSCLC undergoing standard, fractionated radiotherapy alone **Intervention Names:** - Radiation: Radiotherapy **Label:** Cohort 3 #### Arm Group 4 **Description:** Patients with locally advanced NSCLC undergoing standard chemoradiotherapy with the novel signal transduction inhibitor, nelfianvir. **Intervention Names:** - Radiation: Radiotherapy **Label:** Cohort 4 #### Arm Group 5 **Description:** Patients with resectable stage IIIa NSCLC undergoing pre-operative chemoradiotherapy **Intervention Names:** - Radiation: Radiotherapy **Label:** Cohort 5 #### Arm Group 6 **Description:** (Patients with suspected (no tissue diagnosis) early stage NSCLC undergoing stereotactic radiotherapy) **Intervention Names:** - Radiation: Radiotherapy **Label:** Cohort 6 ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1 - Cohort 2 - Cohort 3 - Cohort 4 - Cohort 5 - Cohort 6 **Name:** Radiotherapy **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Measure:** Circulating tumor cells will be detected by imaging for green fluorescent protein (GFP) which measures cells which high levels of telomerase activity after adenovirus transduction. CTCs are measured in units of number of GFP-positive cells /mL. **Time Frame:** 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with biopsy-proven NSCLC who are undergoing definitive radiotherapy as a part of their treatment regimen. * Age 18 or older * Signed informed consent * Patients who are incapable of providing informed consent are excluded from participating in this study. **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** NSCLC patients ### Contacts Locations Module #### Locations **Location 1:** **City:** Philadelphia **Country:** United States **Facility:** Abramson Cancer Center of the University of Pennsylvania **State:** Pennsylvania **Zip:** 19104 #### Overall Officials **Official 1:** **Affiliation:** Abramson Cancer Center at Penn Medicine **Name:** Samuel Swisher McClure, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000009385 - Term: Neoplastic Processes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: Non-Small Cell Lung Cancer - ID: M12305 - Name: Neoplastic Cells, Circulating - Relevance: HIGH - As Found: Circulating Tumor Cells - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung - ID: D000009360 - Term: Neoplastic Cells, Circulating ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2024-04-10 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2024-04-10 - Reset Date: Unknown - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05888779 **Brief Title:** Beverages for Thought: Exploring the Relationship Between Blood Glucose and Cognition **Official Title:** Beverages for Thought: Exploring the Relationship Between Blood Glucose and Cognition #### Organization Study ID Info **ID:** GFHNRC156 #### Organization **Class:** FED **Full Name:** USDA Grand Forks Human Nutrition Research Center ### Status Module #### Completion Date **Date:** 2024-09 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-11 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-09 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09 **Type:** ESTIMATED #### Start Date **Date:** 2023-06-23 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2023-06-05 **Type:** ACTUAL **Study First Submit Date:** 2023-05-04 **Study First Submit QC Date:** 2023-05-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** USDA Grand Forks Human Nutrition Research Center #### Responsible Party **Investigator Affiliation:** USDA Grand Forks Human Nutrition Research Center **Investigator Full Name:** Julie Hess **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of this study is to conduct novel research on the relationship between blood sugar and cognition. **Detailed Description:** This study is an acute parallel study design with one intervention visit needed per participant. There are 2 groups and 80 participants will be randomized into each group. Following the consent process, participants in each group will be seated individually in quiet rooms, with written instructions, several magazines, and a mini-fridge with beverages containing 110-120 kcals/8 fl oz. Participants will be provided instructions for the study, stating, "The study we are conducting explores the relationship between blood glucose and cognitive abilities. After consuming food or drink, your body regulates your blood glucose. Physical exertion can also affect blood glucose. Therefore, we ask that you relax in this space for 10-15 minutes. You can read the provided magazines during this time. Drinking a beverage will bring your body's blood glucose into the right phase for our questionnaires. In the fridge are some beverages, and we ask that you drink something." After 10-15 minutes, participants will be given a cognitive test (a questionnaire on paper) and asked to complete as much of it as they can within 5 minutes. Then, moving to a separate area, weight and height measurements will be taken. ### Conditions Module **Conditions:** - Overweight **Keywords:** - Healthy Weight ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 160 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will consume milk prior to completing a novel cognitive assessment on paper. **Intervention Names:** - Other: Beverage One (Milk) **Label:** Beverage One (Milk) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will consume a fruit drink prior to completing a novel cognitive assessment on paper. **Intervention Names:** - Other: Beverage Two (Juice) **Label:** Beverage Two (Juice) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Beverage One (Milk) **Description:** Participant will consume beverage one (milk) and complete novel cognitive assessment questionnaire on paper. **Name:** Beverage One (Milk) **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Beverage Two (Juice) **Description:** Participant will consume beverage two (fruit drink) and complete novel cognitive assessment questionnaire on paper. **Name:** Beverage Two (Juice) **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Results of cognitive task after consuming a study beverage (milk or fruit-flavored drink). More questions answered correctly results in a higher score. The assessment has a total of 10 questions, and participants will be asked to complete as much of this assessment as they can within a 5 minute timeframe. **Measure:** Written cognitive task results from novel cognitive assessment questionnaire. **Time Frame:** 10 minutes post beverage ingestion ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy weight to overweight (BMI 18.5-29.9 kg/m2) * No food allergies or food intolerances * Healthy (no chronic disease) as determined by online questionnaire * Non-pregnant and non-lactating * Not currently dieting or planning to follow a special diet * Minimal restricted eating practices Exclusion Criteria: * Obesity (BMI ≥ 30 kg/m2) * Pregnant or lactating * Currently dieting or planning to follow a special diet **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** julie.hess@usda.gov **Name:** Julie Hess, PhD **Phone:** 701.795.8146 **Role:** CONTACT **Contact 2:** **Email:** madeline.comeau@usda.gov **Name:** Madeline Comeau, MS **Phone:** 701.795.8361 **Role:** CONTACT #### Locations **Location 1:** **City:** Grand Forks **Contacts:** ***Contact 1:*** - **Email:** angela.scheett@usda.gov - **Name:** Angela J Scheett, MPH, RD - **Phone:** 701-795-8386 - **Role:** CONTACT **Country:** United States **Facility:** USDA Grand Forks Human Nutrition Research Center **State:** North Dakota **Status:** RECRUITING **Zip:** 58203 #### Overall Officials **Official 1:** **Affiliation:** USDA Grand Forks Human Nutrition Research Center **Name:** Julie Hess, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### See Also Links **Label:** Grand Forks Human Nutrition Research Center Current Nutrition Studies **URL:** https://www.ars.usda.gov/plains-area/gfnd/gfhnrc/docs/nutrition-studies/nutrition-studies/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M26186 - Name: Overweight - Relevance: HIGH - As Found: Overweight - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000050177 - Term: Overweight ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06397079 **Brief Title:** Oral Care Program for Residients in Long-term Care Facility **Official Title:** Investigation of Effect on Oral Care Program for Residents in Long-term Care Facility #### Organization Study ID Info **ID:** CTH-113-3-5-004 #### Organization **Class:** OTHER **Full Name:** National Taipei University of Nursing and Health Sciences ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-06 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-02 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-10 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-02 **Type:** ACTUAL **Study First Submit Date:** 2024-04-29 **Study First Submit QC Date:** 2024-04-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** National Taipei University of Nursing and Health Sciences #### Responsible Party **Investigator Affiliation:** National Taipei University of Nursing and Health Sciences **Investigator Full Name:** En-Chi Chiu **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this study is to investigate the effectiveness of an oral care program on the oral hygiene for residents in long-term care facility. **Detailed Description:** The study adopts a randomized clinical trial design and utilizes a cross-over design. The main outcomes include assessments of oral health (Oral Health Assessment Tool, Oral Health Impact Profile, Geriatric Oral Health Assessment Index), tongue coating cleanliness (Tongue Coating Index), dental plaque and gum cleanliness (Plaque Index, Gingival Index, Gingival Bleeding Index), and swallowing ability (Eating Assessment Tool, Function Oral Intake Scale, International Dysphagia Diet Standardisation Initiative). ### Conditions Module **Conditions:** - Elder - Oral Hygiene **Keywords:** - elder - oral hygiene - long-term care facility ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Teach Bass brushing technique and use electric toothbrush **Intervention Names:** - Behavioral: Electric toothbrush **Label:** Electric toothbrush **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Teach Bass brushing technique and use soft bristle toothbrush **Intervention Names:** - Behavioral: Soft bristle toothbrush **Label:** Soft bristle toothbrush **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Electric toothbrush **Description:** Teach Bass brushing technique and bursh teeth using electric toothbrush dental hygiene three times a day. **Name:** Electric toothbrush **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Soft bristle toothbrush **Description:** Teach Bass brushing technique and bursh teeth using soft bristle toothbrush dental hygiene three times a day. **Name:** Soft bristle toothbrush **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** The Oral Health Assessment Tool is a scale for evaluating oral health. The score ranges is 0 to 16. A higher score indicates a poorer oral health condition. **Measure:** Oral Health Assessment Tool **Time Frame:** Baseline to 4 weeks **Description:** The Oral Health Impact Profile assesses the quality of oral health-related life. The score ranges is 0 to 56. A higher score indicates poorer oral health-related quality of life. **Measure:** Oral Health Impact Profile **Time Frame:** Baseline to 4 weeks **Description:** The Geriatric Oral Health Assessment Index evaluates oral health for older people. The score ranges is 12 to 60. A higher score indicates better oral health. **Measure:** Geriatric Oral Health Assessment Index **Time Frame:** Baseline to 4 weeks **Description:** The Tongue Coating Index assesses tongue cleanliness. The score ranges is 0 to 18. A higher core indicates lower cleanliness of the tongue. **Measure:** Tongue Coating Index **Time Frame:** Baseline to 4 weeks **Description:** Plaque Index assesses amount of dental plaque. The score ranges is 0 to 3. A higher score indicates lower amount of dental plaque. **Measure:** Plaque Index **Time Frame:** Baseline to 4 weeks **Description:** The Gingival Index assesses gingival health. The score ranges is 0 to 3. A higher score indicates poorer gingival health. **Measure:** Gingival Index **Time Frame:** Baseline to 4 weeks **Description:** The Gingival Bleeding Index assesses gingival health. The score ranges is 0 to 1. A higher score indicates poorer gingival health. **Measure:** Gingival Bleeding Index **Time Frame:** Baseline to 4 weeks **Description:** The Eating Assessment Tool evaluates the degree of swallowing status. The score ranges is 0 to 40. A higher score indicates lower swallowing ability. **Measure:** Eating Assessment Tool **Time Frame:** Baseline to 4 weeks **Description:** The Functional Oral Intake Scale assesses swallowing ability. The score ranges is 1 to 7. A higher score indicates greater swallowing ability. **Measure:** Function Oral lntake Scale **Time Frame:** Baseline to 4 weeks **Description:** The International Dysphagia Diet Standardisation Initiative assesses swallowing ability. The score ranges is 0 to 7. A higher score indicates greater swallowing ability. **Measure:** International Dysphagia Diet Standardisation Initiative **Time Frame:** Baseline to 4 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Eating by mouth 2. Able to express fluently in Chinese after correcting vision and hearing 3. Normal hand functions 4. Able to follow instructions 5. Willing to participate in the study and sign the informed consent Exclusion Criteria: 1. Unconsicous 2. Diagnosis of dementia and inability to communicate 3. Having a tracheostomy tube and nasogastric tube 4. Unable to move both upper limbs 5. Bedridden 6. Vulnerable populations (e.g., political, economic, or socially disadvantaged groups) **Maximum Age:** 99 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** enchichiu@ntunhs.edu.tw **Name:** En-Chi Chiu, PhD **Phone:** +886-2-28227101 **Phone Ext:** 1291 **Role:** CONTACT #### Locations **Location 1:** **City:** New Taipei City **Contacts:** ***Contact 1:*** - **Email:** enchichiu@ntunhs.edu.tw - **Name:** En-Chi Chiu, PhD - **Phone:** +886-2-28227101 - **Phone Ext:** 1291 - **Role:** CONTACT **Country:** Taiwan **Facility:** Cardinal Tien Hospital **State:** Xindian Dist **Zip:** 231403 #### Overall Officials **Official 1:** **Affiliation:** National Taipei University of Nursing and Health Sciences **Name:** En-Chi Chiu, PhD **Role:** STUDY_DIRECTOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00999479 **Brief Title:** Post Operative Continuous Active Combination Sex Steroids for the Prevention of Recurrent Endometrioma Formation **Official Title:** Post Operative Continuous Active Combination Sex Steroids for the Prevention of Recurrent Endometrioma Formation #### Organization Study ID Info **ID:** Endometrioma #### Organization **Class:** OTHER **Full Name:** University of Oklahoma ### Status Module #### Completion Date **Date:** 2011-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-12-10 **Type:** ESTIMATED **Last Update Submit Date:** 2013-12-09 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2011-10 **Type:** ACTUAL #### Start Date **Date:** 2009-10 **Status Verified Date:** 2013-12 #### Study First Post Date **Date:** 2009-10-21 **Type:** ESTIMATED **Study First Submit Date:** 2009-10-20 **Study First Submit QC Date:** 2009-10-20 **Why Stopped:** Poor enrollment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Oklahoma #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of this study is to determine whether or not continuous combined oral contraceptive pills (COCP's) decrease the risk of recurrent endometrioma formation. The investigators' hypothesis is that patients who have endometriomas surgically removed and then are started on COCP's will have a decreased incidence of recurrent endometrioma formation. The investigators' research protocol is designed to show a statistically significant decreased incidence of endometrioma formation in the hopes that physicians will use COCP's in patients they have removed an endometrioma in who do not desire immediate fertility. Long term, the investigators hope to establish a standard of care that COCP's be used postoperatively in appropriate candidates to decrease the chance of recurrent endometrioma formation. **Detailed Description:** We plan to identify patients planning to undergo conservative surgery for endometrioma at the University of Oklahoma private practice OB/GYN clinic and at the University of Oklahoma Resident Women's clinic. After clear and appropriate consent and discussion regarding options, we plan to randomize patients to monophasic OCPs vs. placebo following surgery. We plan to enroll 35 patients in each arm and follow them for 24 months following the surgery. Surveillance with pelvic exam and transvaginal ultrasonography will occur at 2, 6 and 12 months. The patients surgery will be done prior to enrolling in our study. We will use information from their surgery only to confirm the diagnosis of endometrioma. The only procedure the subjects will undergo during the protocol are periodic transvaginal ultrasonography. ### Conditions Module **Conditions:** - Endometrioma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients randomized to this study arm will receive combined oral contraceptive pills. Patients will follow up at 2, 6, 12, 18 and 24 months. On follow up visits pts will have clinical assessment with vaginal and rectal examinations and with transvaginal ultrasonography. As a measure of compliance, patients will return their empty pill packages **Intervention Names:** - Drug: Norethindrone acetate and ethinyl estradiol tablets, USP **Label:** Monophasic OCP **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients assigned to this arm will use non-hormonal, barrier contraceptives to prevent pregnancy.Patients will follow up at 2, 6, 12, 18 and 24 months. On follow up visits pts will have clinical assessment with vaginal and rectal examinations and with transvaginal ultrasonography. As a measure of compliance, patients will return their empty pill packages. **Intervention Names:** - Drug: ferrous fumarate (placebo) tablets **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Monophasic OCP **Description:** Loestrin® 24 Fe provides a dosage regimen consisting of 24 white progestogen-estrogen contraceptive tablets and 4 brown ferrous fumarate (placebo) tablets. Each white tablet contains 1 mg norethindrone acetate and 20 mcg ethinyl estradiol. Each white tablet also contains the following inactive ingredients: acacia, lactose, magnesium stearate, starch, confectioner's sugar, and talc. **Name:** Norethindrone acetate and ethinyl estradiol tablets, USP **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Loestrin® 24 Fe provides a dosage regimen consisting of 24 white progestogen-estrogen contraceptive tablets and 4 brown ferrous fumarate (placebo) tablets. Each brown tablet contains ferrous fumarate, microcrystalline cellulose, magnesium stearate, povidone, sodium starch glycolate, and compressible sugar. The ferrous fumarate tablets do not serve any therapeutic purpose. **Name:** ferrous fumarate (placebo) tablets **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** To determine whether or not continuous combined oral contraceptive pills decrease the risk of recurrent endometrioma formation. **Time Frame:** October 2011 #### Secondary Outcomes **Measure:** Long term, we hope to establish a standard of care that COCPs be used postoperatively in appropriate candidates to decrease the chance of recurrent endometrioma formation. **Time Frame:** October 2011 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with a diagnosis of ovarian endometriotic cyst that has been surgically excited. Exclusion Criteria: * Current desire to achieve pregnancy or other contraindication to combined oral contraceptive pills. **Healthy Volunteers:** True **Maximum Age:** 35 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Oklahoma City **Country:** United States **Facility:** University of Oklahoma Health Sciences Center **State:** Oklahoma **Zip:** 73104 #### Overall Officials **Official 1:** **Affiliation:** University of Oklahoma **Name:** Katie M Smith, M.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M7877 - Name: Endometriosis - Relevance: HIGH - As Found: Endometrioma - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004715 - Term: Endometriosis ### Intervention Browse Module - Ancestors - ID: D000004967 - Term: Estrogens - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000003270 - Term: Contraceptive Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000003271 - Term: Contraceptive Agents, Female - ID: D000003278 - Term: Contraceptives, Oral, Hormonal - ID: D000003276 - Term: Contraceptives, Oral - ID: D000003280 - Term: Contraceptives, Oral, Synthetic - ID: D000014131 - Term: Trace Elements - ID: D000018977 - Term: Micronutrients ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BlSubst - Name: Blood Substitutes - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: Micro - Name: Micronutrients ### Intervention Browse Module - Browse Leaves - ID: M8116 - Name: Estrogens - Relevance: LOW - As Found: Unknown - ID: M14087 - Name: Povidone - Relevance: LOW - As Found: Unknown - ID: M14244 - Name: Progestins - Relevance: LOW - As Found: Unknown - ID: M8145 - Name: Ethinyl Estradiol - Relevance: HIGH - As Found: Iodine - ID: M266279 - Name: Estradiol 17 beta-cypionate - Relevance: LOW - As Found: Unknown - ID: M266280 - Name: Estradiol 3-benzoate - Relevance: LOW - As Found: Unknown - ID: M8108 - Name: Estradiol - Relevance: HIGH - As Found: Cell lymphoma - ID: M234941 - Name: Polyestradiol phosphate - Relevance: LOW - As Found: Unknown - ID: M12577 - Name: Norethindrone - Relevance: HIGH - As Found: Page - ID: M1841 - Name: Norethindrone Acetate - Relevance: HIGH - As Found: Sexual Dysfunction - ID: M225448 - Name: Ferrous fumarate - Relevance: HIGH - As Found: EMA - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown - ID: M6501 - Name: Contraceptives, Oral, Combined - Relevance: LOW - As Found: Unknown - ID: M266293 - Name: Norinyl - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M2116 - Name: Contraceptive Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown - ID: M6502 - Name: Contraceptives, Oral, Hormonal - Relevance: LOW - As Found: Unknown - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000031621 - Term: Ferrous fumarate - ID: D000004997 - Term: Ethinyl Estradiol - ID: D000009640 - Term: Norethindrone - ID: D000077563 - Term: Norethindrone Acetate - ID: D000004958 - Term: Estradiol ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03706079 **Acronym:** DESTINATION **Brief Title:** Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma **Official Title:** A Multicentre, Double-blind, Randomized, Placebo Controlled, Parallel Group, Phase 3, Safety Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe Uncontrolled Asthma (DESTINATION) #### Organization Study ID Info **ID:** D5180C00018 #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca ### Status Module #### Completion Date **Date:** 2022-05-18 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-06 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-10-26 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-02-09 **Type:** ACTUAL **Results First Submit Date:** 2022-10-24 **Results First Submit QC Date:** 2023-01-11 #### Start Date **Date:** 2019-01-07 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2018-10-15 **Type:** ACTUAL **Study First Submit Date:** 2018-10-11 **Study First Submit QC Date:** 2018-10-11 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Amgen #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** Subjects who completed either D5180C00007 or D5180C00009 will be offered the opportunity to consent for the Multicentre, Double-blind, Randomized, Placebo Controlled, Parallel Group, Phase 3, Safety Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma. The study consists of a treatment phase, followed by a follow-up phase where subjects will not receive IP. The length of the follow up phase is determined by which study the subject had previously completed. **Detailed Description:** Subjects who have not met investigational product discontinuation criteria and have attended the EOT visit in either study D5180C00007 or D5180C00009 will be offered the opportunity to consent for the Multicentre, Double-blind, Randomized, Parallel Group, Placebo Controlled, Phase 3, Safety Extension Study to Evaluate the Safety and Tolerability of Tezepelumab versus placebo in Adults and Adolescents (12 years of age and older) with a history of asthma exacerbations and inadequately controlled severe asthma receiving medium or high dose inhaled corticosteroid (ICS) plus at least one additional asthma controller medication with or without oral corticosteroids Following treatment, subjects will enter a follow-up phase, determined by the predecessor study they had previously completed. Subjects will not receive IP during the follow-up phase. For subjects who entered the study from study D5180C00007 and did not meet IP Discontinuation criteria, the follow-up phase will extend from week 104 to Week 140. Subjects who entered the study from study D5180C00009 will have their follow-up phase extend to week 116. ### Conditions Module **Conditions:** - Asthma **Keywords:** - Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Subjects previously randomized in one of the predecessor studies to tezepelumab will be assigned and remain on tezepelumab dosing in the Destination Study. Subjects randomized to placebo arm in the predecessor studies will be re-randomized in a 1:1 ratio to either tezepelumab or placebo. Given the randomization scheme of subjects in the predecessor studies, this will give an overall subject distribution of 3:1 (tezepelumab:placebo), assuming a similar number of subjects rollover from each arm in the predecessor studies. ##### Masking Info **Masking:** TRIPLE **Masking Description:** Double-Blind **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 951 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Tezepelumab subcutaneous injection **Intervention Names:** - Biological: Tezepelumab **Label:** Tezepelumab **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo: Placebo subcutaneous injection **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Tezepelumab **Description:** Tezepelumab subcutaneous injection **Name:** Tezepelumab **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo subcutaneous injection **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Includes adverse events with an onset date between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set. Exposure adjusted rates are defined as number of subjects with AEs divided by total time at risk across all subjects, multiplied by 100 **Measure:** Exposure Adjusted Incidence Rates of AEs/SAEs **Time Frame:** Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **Description:** Includes time between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set. **Measure:** Total Time at Risk **Time Frame:** Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. #### Secondary Outcomes **Description:** The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set) **Measure:** Annualized Asthma Exacerbation Rate (AAER) **Time Frame:** Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Provision of signed and dated written informed consent * Negative urine test for female subjects of childbearing potential prior to administration of IP at visit 1 * Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from screening, and must agree to continue using such precautions for 16 weeks after the final dose of IP. * Female or male subjects who have not met investigational product discontinuation criteria and have attended the EOT visit in either study D5180C00007 (NAVIGATOR) or D5180C00009 (SOURCE) To enter the extended follow-up phase of the study, the following inclusion criteria also apply: * Provision of signed and dated Addendum for Extended Follow-up to informed consent, as well as assent by adolescent subjects where applicable, prior to any mandatory study specific procedures, sampling and analyses before Extended Follow Up. * Must have entered DESTINATION from D5180C00007 study and have completed IP dosing to Week 100, have not met IP Discontinuation criteria and have attended the EOT Visit. Exclusion Criteria: * Any clinically important pulmonary disease other than asthma * Any disorder, including, but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable * History of chronic alcohol or drug abuse within 12 months prior to visit 1 * Current malignancy or malignancy that developed during a predecessor study * Major surgery or planned surgical procedures requiring general anesthesia or inpatient status for \> 1 day during the conduct of the study * Treatment with systemic immunosuppressive/immunomodulating drugs except for OCS used in the treatment of asthma/asthma exacerbations within the last 12 weeks prior to randomization * Concurrent enrolment in another clinical study involving an IP * Any clinically meaningful abnormal finding in physical examination, vital signs, ECG,haematology, clinical chemistry, or urinalysis during the predecessor study * Pregnant, breastfeeding, or lactating To enter the extended follow-up phase of the study (which extends from week 104 to week 140), the following exclusion criteria also apply: * Discontinuation of IP during the treatment period of DESTINATION. * Entered DESTINATION from D5180C00009 (SOURCE) study. **Maximum Age:** 81 Years **Minimum Age:** 13 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Dothan **Country:** United States **Facility:** Research Site **State:** Alabama **Zip:** 36303 **Location 2:** **City:** Gilbert **Country:** United States **Facility:** Research Site **State:** Arizona **Zip:** 85234 **Location 3:** **City:** Bakersfield **Country:** United States **Facility:** Research Site **State:** California **Zip:** 93301 **Location 4:** **City:** Huntington Beach **Country:** United States **Facility:** Research Site **State:** California **Zip:** 92647 **Location 5:** **City:** Long Beach **Country:** United States **Facility:** Research Site **State:** California **Zip:** 90808 **Location 6:** **City:** Los Angeles **Country:** United States **Facility:** Research Site **State:** California **Zip:** 90025 **Location 7:** **City:** Newport Beach **Country:** United States **Facility:** Research Site **State:** California **Zip:** 92663 **Location 8:** **City:** Northridge **Country:** United States **Facility:** Research Site **State:** California **Zip:** 91324 **Location 9:** **City:** Palm Desert **Country:** United States **Facility:** Research Site **State:** California **Zip:** 92260 **Location 10:** **City:** Rolling Hills Estates **Country:** United States **Facility:** Research Site **State:** California **Zip:** 90274 **Location 11:** **City:** Walnut Creek **Country:** United States **Facility:** Research Site **State:** California **Zip:** 94598 **Location 12:** **City:** Westminster **Country:** United States **Facility:** Research Site **State:** California **Zip:** 92683 **Location 13:** **City:** New Haven **Country:** United States **Facility:** Research Site **State:** Connecticut **Zip:** 06519 **Location 14:** **City:** Kissimmee **Country:** United States **Facility:** Research Site **State:** Florida **Zip:** 34744 **Location 15:** **City:** Kissimmee **Country:** United States **Facility:** Research Site **State:** Florida **Zip:** 34746 **Location 16:** **City:** Port Charlotte **Country:** United States **Facility:** Research Site **State:** Florida **Zip:** 33952 **Location 17:** **City:** Sarasota **Country:** United States **Facility:** Research Site **State:** Florida **Zip:** 34239 **Location 18:** **City:** Tampa **Country:** United States **Facility:** Research Site **State:** Florida **Zip:** 33607 **Location 19:** **City:** Winter Park **Country:** United States **Facility:** Research Site **State:** Florida **Zip:** 32789-4681 **Location 20:** **City:** Boise **Country:** United States **Facility:** Research Site **State:** Idaho **Zip:** 83706 **Location 21:** **City:** Zachary **Country:** United States **Facility:** Research Site **State:** Louisiana **Zip:** 70791 **Location 22:** **City:** White Marsh **Country:** United States **Facility:** Research Site **State:** Maryland **Zip:** 21162 **Location 23:** **City:** Boston **Country:** United States **Facility:** Research Site **State:** Massachusetts **Zip:** 02115 **Location 24:** **City:** Ann Arbor **Country:** United States **Facility:** Research Site **State:** Michigan **Zip:** 48109 **Location 25:** **City:** Saint Louis **Country:** United States **Facility:** Research Site **State:** Missouri **Zip:** 63141 **Location 26:** **City:** Lincoln **Country:** United States **Facility:** Research Site **State:** Nebraska **Zip:** 68510 **Location 27:** **City:** Las Vegas **Country:** United States **Facility:** Research Site **State:** Nevada **Zip:** 89119 **Location 28:** **City:** Northfield **Country:** United States **Facility:** Research Site **State:** New Jersey **Zip:** 08225 **Location 29:** **City:** Bronx **Country:** United States **Facility:** Research Site **State:** New York **Zip:** 10459 **Location 30:** **City:** Bronx **Country:** United States **Facility:** Research Site **State:** New York **Zip:** 10461 **Location 31:** **City:** Brooklyn **Country:** United States **Facility:** Research Site **State:** New York **Zip:** 11235 **Location 32:** **City:** Charlotte **Country:** United States **Facility:** Research Site **State:** North Carolina **Zip:** 28207 **Location 33:** **City:** Durham **Country:** United States **Facility:** Research Site **State:** North Carolina **Zip:** 27705 **Location 34:** **City:** Winston-Salem **Country:** United States **Facility:** Research Site **State:** North Carolina **Zip:** 27104 **Location 35:** **City:** Cincinnati **Country:** United States **Facility:** Research Site **State:** Ohio **Zip:** 45229 **Location 36:** **City:** Cincinnati **Country:** United States **Facility:** Research Site **State:** Ohio **Zip:** 45236 **Location 37:** **City:** Edmond **Country:** United States **Facility:** Research Site **State:** Oklahoma **Zip:** 73034 **Location 38:** **City:** Oklahoma City **Country:** United States **Facility:** Research Site **State:** Oklahoma **Zip:** 73120 **Location 39:** **City:** Medford **Country:** United States **Facility:** Research Site **State:** Oregon **Zip:** 97504 **Location 40:** **City:** Philadelphia **Country:** United States **Facility:** Research Site **State:** Pennsylvania **Zip:** 19140 **Location 41:** **City:** Anderson **Country:** United States **Facility:** Research Site **State:** South Carolina **Zip:** 29621 **Location 42:** **City:** Columbia **Country:** United States **Facility:** Research Site **State:** South Carolina **Zip:** 29204 **Location 43:** **City:** Greenville **Country:** United States **Facility:** Research Site **State:** South Carolina **Zip:** 29607 **Location 44:** **City:** Amarillo **Country:** United States **Facility:** Research Site **State:** Texas **Zip:** 79109 **Location 45:** **City:** Boerne **Country:** United States **Facility:** Research Site **State:** Texas **Zip:** 78006 **Location 46:** **City:** McKinney **Country:** United States **Facility:** Research Site **State:** Texas **Zip:** 75069 **Location 47:** **City:** McKinney **Country:** United States **Facility:** Research Site **State:** Texas **Zip:** 75071 **Location 48:** **City:** Plano **Country:** United States **Facility:** Research Site **State:** Texas **Zip:** 75093 **Location 49:** **City:** San Antonio **Country:** United States **Facility:** Research Site **State:** Texas **Zip:** 78251 **Location 50:** **City:** Manassas **Country:** United States **Facility:** Research Site **State:** Virginia **Zip:** 20110 **Location 51:** **City:** Cudahy **Country:** United States **Facility:** Research Site **State:** Wisconsin **Zip:** 53110 **Location 52:** **City:** Madison **Country:** United States **Facility:** Research Site **State:** Wisconsin **Zip:** 53792 **Location 53:** **City:** Buenos Aires **Country:** Argentina **Facility:** Research Site **Zip:** 1027 **Location 54:** **City:** Buenos Aires **Country:** Argentina **Facility:** Research Site **Zip:** C1414AIF **Location 55:** **City:** Caba **Country:** Argentina **Facility:** Research Site **Zip:** C1425BEN **Location 56:** **City:** Ciudad de Buenos Aires **Country:** Argentina **Facility:** Research Site **Zip:** 1425 **Location 57:** **City:** Córdoba **Country:** Argentina **Facility:** Research Site **Zip:** X5003DCE **Location 58:** **City:** Mendoza **Country:** Argentina **Facility:** Research Site **Zip:** 5500 **Location 59:** **City:** Nueve de julio **Country:** Argentina **Facility:** Research Site **Zip:** B6500EZL **Location 60:** **City:** Quilmes **Country:** Argentina **Facility:** Research Site **Zip:** B1878FNR **Location 61:** **City:** San Fernando **Country:** Argentina **Facility:** Research Site **Zip:** B1646EBJ **Location 62:** **City:** San Miguel de Tucuman **Country:** Argentina **Facility:** Research Site **Zip:** T4000IAQ **Location 63:** **City:** Kent Town **Country:** Australia **Facility:** Research Site **Zip:** 5067 **Location 64:** **City:** Melbourne **Country:** Australia **Facility:** Research Site **Zip:** 3004 **Location 65:** **City:** New Lambton **Country:** Australia **Facility:** Research Site **Zip:** 2310 **Location 66:** **City:** Spearwood **Country:** Australia **Facility:** Research Site **Zip:** 6163 **Location 67:** **City:** Westmead **Country:** Australia **Facility:** Research Site **Zip:** 2145 **Location 68:** **City:** Woolloongabba **Country:** Australia **Facility:** Research Site **Zip:** 4102 **Location 69:** **City:** Wien **Country:** Austria **Facility:** Research Site **Zip:** 1090 **Location 70:** **City:** Wien **Country:** Austria **Facility:** Research Site **Zip:** 1130 **Location 71:** **City:** Blumenau **Country:** Brazil **Facility:** Research Site **Zip:** 89030-101 **Location 72:** **City:** Botucatu **Country:** Brazil **Facility:** Research Site **Zip:** 18618-970 **Location 73:** **City:** Curitiba **Country:** Brazil **Facility:** Research Site **Zip:** 80060-900 **Location 74:** **City:** Porto Alegre **Country:** Brazil **Facility:** Research Site **Zip:** 9002-060 **Location 75:** **City:** Porto Alegre **Country:** Brazil **Facility:** Research Site **Zip:** 90020-090 **Location 76:** **City:** Porto Alegre **Country:** Brazil **Facility:** Research Site **Zip:** 90610-000 **Location 77:** **City:** Porto Alegre **Country:** Brazil **Facility:** Research Site **Zip:** 91350-200 **Location 78:** **City:** Recife **Country:** Brazil **Facility:** Research Site **Zip:** 50070-550 **Location 79:** **City:** Salvador **Country:** Brazil **Facility:** Research Site **Zip:** 40060-330 **Location 80:** **City:** Santo Andre **Country:** Brazil **Facility:** Research Site **Zip:** 09080-110 **Location 81:** **City:** Sao Bernardo do Campo **Country:** Brazil **Facility:** Research Site **Zip:** 09750-420 **Location 82:** **City:** Sorocaba **Country:** Brazil **Facility:** Research Site **Zip:** 18040-425 **Location 83:** **City:** Calgary **Country:** Canada **Facility:** Research Site **State:** Alberta **Zip:** T2N 4Z6 **Location 84:** **City:** Sherwood Park **Country:** Canada **Facility:** Research Site **State:** Alberta **Zip:** T8L 0N2 **Location 85:** **City:** Ajax **Country:** Canada **Facility:** Research Site **State:** Ontario **Zip:** L1S 2J5 **Location 86:** **City:** Mississauga **Country:** Canada **Facility:** Research Site **State:** Ontario **Zip:** L5A 3V4 **Location 87:** **City:** Ottawa **Country:** Canada **Facility:** Research Site **State:** Ontario **Zip:** K1H 1E4 **Location 88:** **City:** Windsor **Country:** Canada **Facility:** Research Site **State:** Ontario **Zip:** N8X 1T3 **Location 89:** **City:** Montreal **Country:** Canada **Facility:** Research Site **State:** Quebec **Zip:** H4J 1C5 **Location 90:** **City:** St Charles Borromee **Country:** Canada **Facility:** Research Site **State:** Quebec **Zip:** J6E 2B4 **Location 91:** **City:** Trois-Rivières **Country:** Canada **Facility:** Research Site **State:** Quebec **Zip:** G8T 7A1 **Location 92:** **City:** Quebec **Country:** Canada **Facility:** Research Site **Zip:** G1G 3Y8 **Location 93:** **City:** Brest Cedex 2 **Country:** France **Facility:** Research Site **Zip:** 29609 **Location 94:** **City:** Le Kremlin-Bicêtre **Country:** France **Facility:** Research Site **Zip:** 94270 **Location 95:** **City:** Lyon Cedex 04 **Country:** France **Facility:** Research Site **Zip:** 69317 **Location 96:** **City:** Marseille Cedex 20 **Country:** France **Facility:** Research Site **Zip:** 13915 **Location 97:** **City:** Montpellier **Country:** France **Facility:** Research Site **Zip:** 34090 **Location 98:** **City:** Nantes **Country:** France **Facility:** Research Site **Zip:** 44093 **Location 99:** **City:** Paris **Country:** France **Facility:** Research Site **Zip:** 75012 **Location 100:** **City:** Paris **Country:** France **Facility:** Research Site **Zip:** 75018 **Location 101:** **City:** Pessac **Country:** France **Facility:** Research Site **Zip:** 33604 **Location 102:** **City:** Strasbourg Cedex **Country:** France **Facility:** Research Site **Zip:** 67091 **Location 103:** **City:** Bamberg **Country:** Germany **Facility:** Research Site **Zip:** 96049 **Location 104:** **City:** Berlin **Country:** Germany **Facility:** Research Site **Zip:** 10367 **Location 105:** **City:** Berlin **Country:** Germany **Facility:** Research Site **Zip:** 10717 **Location 106:** **City:** Berlin **Country:** Germany **Facility:** Research Site **Zip:** 10969 **Location 107:** **City:** Frankfurt am Main **Country:** Germany **Facility:** Research Site **Zip:** 60596 **Location 108:** **City:** Frankfurt **Country:** Germany **Facility:** Research Site **Zip:** 60596 **Location 109:** **City:** Hamburg **Country:** Germany **Facility:** Research Site **Zip:** 20354 **Location 110:** **City:** Hamburg **Country:** Germany **Facility:** Research Site **Zip:** 22299 **Location 111:** **City:** Hannover **Country:** Germany **Facility:** Research Site **Zip:** 30625 **Location 112:** **City:** Hannover **Country:** Germany **Facility:** Research Site **Zip:** D-30173 **Location 113:** **City:** Koblenz **Country:** Germany **Facility:** Research Site **Zip:** 56068 **Location 114:** **City:** Landsberg **Country:** Germany **Facility:** Research Site **Zip:** 86899 **Location 115:** **City:** Leipzig **Country:** Germany **Facility:** Research Site **Zip:** 04357 **Location 116:** **City:** Lübeck **Country:** Germany **Facility:** Research Site **Zip:** 23552 **Location 117:** **City:** Mainz **Country:** Germany **Facility:** Research Site **Zip:** 55131 **Location 118:** **City:** Ashkelon **Country:** Israel **Facility:** Research Site **Zip:** 7830604 **Location 119:** **City:** Haifa **Country:** Israel **Facility:** Research Site **Zip:** 34362 **Location 120:** **City:** Jerusalem **Country:** Israel **Facility:** Research Site **Zip:** 91031 **Location 121:** **City:** Jerusalem **Country:** Israel **Facility:** Research Site **Zip:** 91120 **Location 122:** **City:** Kfar Saba **Country:** Israel **Facility:** Research Site **Zip:** 49281 **Location 123:** **City:** Rehovot **Country:** Israel **Facility:** Research Site **Zip:** 7661041 **Location 124:** **City:** Bucheon-si **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 420-767 **Location 125:** **City:** Cheongju-si **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 28644 **Location 126:** **City:** Daegu **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 41404 **Location 127:** **City:** Daegu **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 42415 **Location 128:** **City:** Jeju-do **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 63241 **Location 129:** **City:** Jeonju-si **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 54907 **Location 130:** **City:** Seongnam-si **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 13620 **Location 131:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 02447 **Location 132:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 03312 **Location 133:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 03722 **Location 134:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 05505 **Location 135:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 06351 **Location 136:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 06591 **Location 137:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 08308 **Location 138:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 150-713 **Location 139:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 158-710 **Location 140:** **City:** Suwon-si **Country:** Korea, Republic of **Facility:** Research Site **Zip:** 16499 **Location 141:** **City:** Kraków **Country:** Poland **Facility:** Research Site **Zip:** 31-559 **Location 142:** **City:** Wrocław **Country:** Poland **Facility:** Research Site **Zip:** 53-301 **Location 143:** **City:** Łódź **Country:** Poland **Facility:** Research Site **Zip:** 90-153 **Location 144:** **City:** Izhevsk **Country:** Russian Federation **Facility:** Research Site **Zip:** 426035 **Location 145:** **City:** Moscow **Country:** Russian Federation **Facility:** Research Site **Zip:** 115093 **Location 146:** **City:** Moscow **Country:** Russian Federation **Facility:** Research Site **Zip:** 115522 **Location 147:** **City:** St-Petersburg **Country:** Russian Federation **Facility:** Research Site **Zip:** 193231 **Location 148:** **City:** Jeddah **Country:** Saudi Arabia **Facility:** Research Site **Zip:** 21423 **Location 149:** **City:** Jeddah **Country:** Saudi Arabia **Facility:** Research Site **Zip:** 22252 **Location 150:** **City:** Bellville **Country:** South Africa **Facility:** Research Site **Zip:** 7530 **Location 151:** **City:** Cape Town **Country:** South Africa **Facility:** Research Site **Zip:** 7700 **Location 152:** **City:** Cape Town **Country:** South Africa **Facility:** Research Site **Zip:** 7764 **Location 153:** **City:** Durban **Country:** South Africa **Facility:** Research Site **Zip:** 4001 **Location 154:** **City:** Durban **Country:** South Africa **Facility:** Research Site **Zip:** 4091 **Location 155:** **City:** Durban **Country:** South Africa **Facility:** Research Site **Zip:** 4092 **Location 156:** **City:** Durban **Country:** South Africa **Facility:** Research Site **Zip:** 4450 **Location 157:** **City:** Johannesburg **Country:** South Africa **Facility:** Research Site **Zip:** 1724 **Location 158:** **City:** Johannesburg **Country:** South Africa **Facility:** Research Site **Zip:** 1829 **Location 159:** **City:** Johannesburg **Country:** South Africa **Facility:** Research Site **Zip:** 2113 **Location 160:** **City:** Lenasia Ext8 **Country:** South Africa **Facility:** Research Site **Zip:** 1820 **Location 161:** **City:** Meadowdale, Germiston **Country:** South Africa **Facility:** Research Site **Zip:** 1614 **Location 162:** **City:** Middelburg **Country:** South Africa **Facility:** Research Site **Zip:** 1055 **Location 163:** **City:** Parow **Country:** South Africa **Facility:** Research Site **Zip:** 7505 **Location 164:** **City:** Umkomaas **Country:** South Africa **Facility:** Research Site **Zip:** 4170 **Location 165:** **City:** Kaohsiung **Country:** Taiwan **Facility:** Research Site **Zip:** 80756 **Location 166:** **City:** Taichung **Country:** Taiwan **Facility:** Research Site **Zip:** 40447 **Location 167:** **City:** Taipei **Country:** Taiwan **Facility:** Research Site **Zip:** 235 **Location 168:** **City:** Ankara **Country:** Turkey **Facility:** Research Site **Zip:** 06230 **Location 169:** **City:** Ankara **Country:** Turkey **Facility:** Research Site **Zip:** 06280 **Location 170:** **City:** Bursa **Country:** Turkey **Facility:** Research Site **Zip:** 16059 **Location 171:** **City:** Istanbul **Country:** Turkey **Facility:** Research Site **Zip:** 34098 **Location 172:** **City:** Dnipro **Country:** Ukraine **Facility:** Research Site **Zip:** 49007 **Location 173:** **City:** Ivano-Frankivsk **Country:** Ukraine **Facility:** Research Site **Zip:** 76018 **Location 174:** **City:** Kharkiv Region **Country:** Ukraine **Facility:** Research Site **Zip:** 61075 **Location 175:** **City:** Kherson **Country:** Ukraine **Facility:** Research Site **Zip:** 73000 **Location 176:** **City:** Lutsk **Country:** Ukraine **Facility:** Research Site **Zip:** 43000 **Location 177:** **City:** Vinnytsia **Country:** Ukraine **Facility:** Research Site **Zip:** 21029 **Location 178:** **City:** Ha Noi **Country:** Vietnam **Facility:** Research Site **Zip:** 100000 **Location 179:** **City:** Hanoi **Country:** Vietnam **Facility:** Research Site **Zip:** 10000 **Location 180:** **City:** Ho Chi Minh **Country:** Vietnam **Facility:** Research Site **Zip:** 700000 #### Overall Officials **Official 1:** **Affiliation:** Royal Brompton Hospital, United Kingdom **Name:** Andrew Menzies-Gow, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Menzies-Gow A, Ponnarambil S, Downie J, Bowen K, Hellqvist A, Colice G. DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res. 2020 Oct 21;21(1):279. doi: 10.1186/s12931-020-01541-7. **PMID:** 33087119 #### See Also Links **Label:** Statistical Analysis Plan (SAP) **URL:** https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5180C00018&amp;attachmentIdentifier=8a2b972e-4a6e-43c5-af7a-ae92fb0c49f3&amp;fileName=d5180c00018-sap-ed-3-redact.pdf&amp;versionIdentifier= **Label:** Protocol **URL:** https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5180C00018&amp;attachmentIdentifier=50cb4a27-8cdd-456e-8557-fdeccbd69d40&amp;fileName=d5180c00018-csp-v6-redact.pdf&amp;versionIdentifier= **Label:** CSR Synopsis **URL:** https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5180C00018&amp;attachmentIdentifier=d7be4478-ea53-4972-9b54-6771c586611a&amp;fileName=d5180c00018-study-synopsis-redact.pdf&amp;versionIdentifier= ## Document Section ### Large Document Module #### Large Docs - Date: 2021-04-12 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1878920 - Type Abbrev: Prot - Upload Date: 2022-10-24T07:03 - Date: 2021-11-03 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 983432 - Type Abbrev: SAP - Upload Date: 2022-10-24T07:03 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001982 - Term: Bronchial Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000008171 - Term: Lung Diseases - ID: D000012130 - Term: Respiratory Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4556 - Name: Asthma - Relevance: HIGH - As Found: Asthma - ID: M5258 - Name: Bronchial Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14967 - Name: Respiratory Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001249 - Term: Asthma ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2022-11-17 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** The subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION are included in both Rand Pbo and Pbo to Teze arms. Their data collected during the placebo (predecessor) period are contained within the Rand Pbo arm, while data collected after the first dose of tezepelumab in DESTINATION are presented in the Pbo to Teze arm. Note the primary objective in the Outcome Measures section presents on-treatment safety as opposed to on-study safety. #### Event Groups **Group ID:** EG000 **Title:** NAVIGATOR Rand Teze **Deaths Num Affected:** 8 **Deaths Num At Risk:** 528 **Description:** All subjects randomised to tezepelumab in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** EG000 **Other Num Affected:** 390 **Other Num at Risk:** 528 **Serious Number Affected:** 82 **Serious Number At Risk:** 528 **Title:** NAVIGATOR Rand Teze **Group ID:** EG001 **Title:** NAVIGATOR Rand Pbo **Deaths Num Affected:** 5 **Deaths Num At Risk:** 531 **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching to tezepelumab in DESTINATION, data collected during the placebo (predecessor) period are contained in this column, while data collected after the first dose of tezepelumab in DESTINATION are presented in the NAVIGATOR Pbo to Teze arm. **ID:** EG001 **Other Num Affected:** 384 **Other Num at Risk:** 531 **Serious Number Affected:** 94 **Serious Number At Risk:** 531 **Title:** NAVIGATOR Rand Pbo **Group ID:** EG002 **Title:** NAVIGATOR Pbo to Teze **Deaths Num Affected:** 1 **Deaths Num At Risk:** 206 **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and re-randomised to tezepelumab in DESTINATION. Only data collected after the first dose of tezepelumab in DESTINATION are presented in this column. **ID:** EG002 **Other Num Affected:** 98 **Other Num at Risk:** 206 **Serious Number Affected:** 17 **Serious Number At Risk:** 206 **Title:** NAVIGATOR Pbo to Teze **Group ID:** EG003 **Title:** SOURCE Rand Teze **Deaths Num Affected:** 2 **Deaths Num At Risk:** 74 **Description:** All subjects randomised to tezepelumab in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** EG003 **Other Num Affected:** 53 **Other Num at Risk:** 74 **Serious Number Affected:** 18 **Serious Number At Risk:** 74 **Title:** SOURCE Rand Teze **Group ID:** EG004 **Title:** SOURCE Rand Pbo **Deaths Num At Risk:** 76 **Description:** All subjects randomised to placebo in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching to tezepelumab in DESTINATION, data collected during the placebo (predecessor) period are contained in this column, while data collected after the first dose of tezepelumab in DESTINATION are presented in the SOURCE Pbo to Teze arm. **ID:** EG004 **Other Num Affected:** 58 **Other Num at Risk:** 76 **Serious Number Affected:** 19 **Serious Number At Risk:** 76 **Title:** SOURCE Rand Pbo **Group ID:** EG005 **Title:** SOURCE Pbo to Teze **Deaths Num At Risk:** 32 **Description:** All subjects randomised to placebo in the SOURCE predecessor and re-randomised to tezepelumab in DESTINATION. Only data collected after the first dose of tezepelumab in DESTINATION are presented in this column. **ID:** EG005 **Other Num Affected:** 23 **Other Num at Risk:** 32 **Serious Number Affected:** 4 **Serious Number At Risk:** 32 **Title:** SOURCE Pbo to Teze **Frequency Threshold:** 3 #### Other Events **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Traumatic haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 **Term:** Rhinitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Sinusitis bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Upper respiratory tract infection bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Vaginal infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Hyperlipidaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Type 2 diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Vertebral foraminal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Hyposmia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Spinal cord disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Gastrooesophageal reflux disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Cholelithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Acute sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Bronchitis bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Bronchitis viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Oral candidiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Pharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Pneumonia haemophilus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Suspected covid-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Tinea versicolour **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Viral rhinitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Viral upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Vulval abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Contusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 **Term:** Facial bones fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 **Term:** Joint dislocation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 **Term:** Ligament sprain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 **Term:** Glucose tolerance impaired **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Spinal osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Anosmia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Cerebral arteriosclerosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Cerebrovascular disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Asthma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Nasal polyps **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Rhinitis allergic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Sleep apnoea syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Acne **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Dry skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Photodermatosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Rash macular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Cataract **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Retinal tear **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Dental caries **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Dyspepsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Impaired healing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Influenza like illness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Hypersensitivity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Covid-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Chronic sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Cystitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Lower respiratory tract infection bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Otitis media **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 #### Serious Events **Term:** Cardiac failure congestive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Viral upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Head injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Hip fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Coronary artery disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ligament sprain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Lower limb fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Periprocedural myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Radius fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Road traffic accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Skin laceration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Coronary artery occlusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ulna fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ligament rupture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 528 **Num Events:** 3 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Spinal compression fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Tendon rupture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Tibia fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Blood creatine phosphokinase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Diabetes mellitus inadequate control **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Diabetic ketoacidosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Muscle necrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Myocarditis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gout **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Myositis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Type 1 diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Amyotrophy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Bone cyst **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Exostosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Intervertebral disc protrusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Lumbar spinal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Muscle spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Invasive breast carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Polyarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Prinzmetal angina **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Squamous cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Spinal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Spondylolisthesis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Supraventricular tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 2 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ventricular extrasystoles **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Encephalocele **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Immune thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Hypertrophic cardiomyopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Vertigo positional **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cataract **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Anal fistula **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Uveitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Diverticular perforation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Acute left ventricular failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gastric polyps **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Ileus paralytic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Inguinal hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 3 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Large intestine polyp **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Rectal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Oesophageal achalasia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pancreatitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pancreatitis necrotising **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 531 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Impaired healing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Aortic valve stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cholecystitis chronic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Anaphylactic reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cholecystitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Drug-induced liver injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Drug hypersensitivity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Atrial flutter **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Breast abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Bacterial pyelonephritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Atrial tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Covid-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 528 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Covid-19 pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 528 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 3 **Num At Risk:** 74 **Num Events:** 3 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** H1n1 influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gastroenteritis viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cardiac arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Intervertebral discitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Lower respiratory tract infection bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 5 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Meningitis bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 528 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia haemophilus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Cardiac failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Osteomyelitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia streptococcal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Periorbital cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 76 **Num Events:** 2 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia klebsiella **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ovarian germ cell teratoma benign **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Basal cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Benign neoplasm of thyroid gland **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Colon adenoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Colon cancer stage iv **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Endometrial cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Malignant melanoma in situ **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Neurilemmoma benign **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Prostate cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Prostatic adenoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Squamous cell carcinoma of the oral cavity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Thymoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Uterine leiomyoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Glomerulonephritis membranous **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Renal colic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cubital tunnel syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Haemorrhagic stroke **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Asthma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 14 **Num At Risk:** 528 **Num Events:** 18 **Group ID:** EG001 **Num Affected:** 41 **Num At Risk:** 531 **Num Events:** 79 **Group ID:** EG002 **Num Affected:** 5 **Num At Risk:** 206 **Num Events:** 6 **Group ID:** EG003 **Num Affected:** 3 **Num At Risk:** 74 **Num Events:** 5 **Group ID:** EG004 **Num Affected:** 8 **Num At Risk:** 76 **Num Events:** 11 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Idiopathic generalised epilepsy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Intracranial aneurysm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Lumbar radiculopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Migraine **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Myelopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ruptured cerebral aneurysm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Transient ischaemic attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 32 **Num Events:** 1 **Term:** Disruptive mood dysregulation disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Obstruction gastric **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Chest discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Malaise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Atypical pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cholecystitis infective **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Herpes zoster oticus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Diverticulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gastroenteritis salmonella **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Septic shock **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Incisional hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Lumbar vertebral fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Type 2 diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Colorectal cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Seizure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Abortion spontaneous **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Pregnancy, puerperium and perinatal conditions **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Bipolar disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 74 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ureterolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Benign prostatic hyperplasia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Ovarian cyst **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Uterine prolapse **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Asthma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 16 **Num At Risk:** 528 **Num Events:** 20 **Group ID:** EG001 **Num Affected:** 43 **Num At Risk:** 531 **Num Events:** 91 **Group ID:** EG002 **Num Affected:** 5 **Num At Risk:** 206 **Num Events:** 6 **Group ID:** EG003 **Num Affected:** 5 **Num At Risk:** 74 **Num Events:** 7 **Group ID:** EG004 **Num Affected:** 8 **Num At Risk:** 76 **Num Events:** 12 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Bronchial secretion retention **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Eosinophilic pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Haemothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Nasal polyps **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pulmonary embolism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pulmonary sarcoidosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Hyperparathyroidism primary **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Dermatitis contact **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cyanosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Peripheral arterial occlusive disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Thrombosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Colitis ischaemic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Umbilical hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 76 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Gait disturbance **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cholecystitis chronic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 206 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Cholelithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 528 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Anal abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Appendicitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Lower respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Lung abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 528 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 531 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia aspiration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Term:** Pneumonia staphylococcal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 531 **Group ID:** EG002 **Num At Risk:** 206 **Group ID:** EG003 **Num At Risk:** 74 **Group ID:** EG004 **Num At Risk:** 76 **Group ID:** EG005 **Num At Risk:** 32 **Time Frame:** Baseline (Week 0 in predecessor study) to long-term extension completion (either weeks 104 or 116). Includes AEs with onset date between the date of first dose of IP and and the long-term extension completion or withdrawal date (on-study period) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 528 **Group ID:** BG001 **Value:** 531 **Group ID:** BG002 **Value:** 74 **Group ID:** BG003 **Value:** 76 **Group ID:** BG004 **Value:** 1209 **Units:** Participants ### Group **ID:** BG000 **Title:** NAVIGATOR Rand Teze **Description:** All subjects randomised to tezepelumab in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. ### Group **ID:** BG001 **Title:** NAVIGATOR Rand Pbo **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study and regardless of their treatment assignment in DESTINATION. ### Group **ID:** BG002 **Title:** SOURCE Rand Teze **Description:** All subjects randomised to tezepelumab in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. ### Group **ID:** BG003 **Title:** SOURCE Rand Pbo **Description:** All subjects randomised to placebo in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study and regardless of their treatment assignment in DESTINATION. ### Group **ID:** BG004 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 41 #### Measurement **Group ID:** BG001 **Value:** 41 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 82 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 391 #### Measurement **Group ID:** BG001 **Value:** 416 #### Measurement **Group ID:** BG002 **Value:** 58 #### Measurement **Group ID:** BG003 **Value:** 62 #### Measurement **Group ID:** BG004 **Value:** 927 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 96 #### Measurement **Group ID:** BG001 **Value:** 74 #### Measurement **Group ID:** BG002 **Value:** 16 #### Measurement **Group ID:** BG003 **Value:** 14 #### Measurement **Group ID:** BG004 **Value:** 200 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 16.3 **Value:** 49.9 #### Measurement **Group ID:** BG001 **Spread:** 15.9 **Value:** 49.0 #### Measurement **Group ID:** BG002 **Spread:** 12.1 **Value:** 53.5 #### Measurement **Group ID:** BG003 **Spread:** 11.9 **Value:** 53.4 #### Measurement **Group ID:** BG004 **Spread:** 15.7 **Value:** 49.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 335 #### Measurement **Group ID:** BG001 **Value:** 337 #### Measurement **Group ID:** BG002 **Value:** 49 #### Measurement **Group ID:** BG003 **Value:** 45 #### Measurement **Group ID:** BG004 **Value:** 766 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 193 #### Measurement **Group ID:** BG001 **Value:** 194 #### Measurement **Group ID:** BG002 **Value:** 25 #### Measurement **Group ID:** BG003 **Value:** 31 #### Measurement **Group ID:** BG004 **Value:** 443 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 83 #### Measurement **Group ID:** BG001 **Value:** 81 #### Measurement **Group ID:** BG002 **Value:** 10 #### Measurement **Group ID:** BG003 **Value:** 14 #### Measurement **Group ID:** BG004 **Value:** 188 **Class Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 445 #### Measurement **Group ID:** BG001 **Value:** 450 #### Measurement **Group ID:** BG002 **Value:** 64 #### Measurement **Group ID:** BG003 **Value:** 62 #### Measurement **Group ID:** BG004 **Value:** 1021 **Class Title:** Not Hispanic or Latino ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 1 **Class Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 146 #### Measurement **Group ID:** BG001 **Value:** 149 #### Measurement **Group ID:** BG002 **Value:** 11 #### Measurement **Group ID:** BG003 **Value:** 11 #### Measurement **Group ID:** BG004 **Value:** 317 **Class Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 30 #### Measurement **Group ID:** BG001 **Value:** 31 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 62 **Class Title:** Black of African American #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 1 **Class Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 19 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 43 **Class Title:** Other #### Measurement **Group ID:** BG000 **Value:** 332 #### Measurement **Group ID:** BG001 **Value:** 327 #### Measurement **Group ID:** BG002 **Value:** 62 #### Measurement **Group ID:** BG003 **Value:** 64 #### Measurement **Group ID:** BG004 **Value:** 785 **Class Title:** White **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Restrictive Agreement:** True ### Point of Contact **Email:** information.center@astrazeneca.com **Organization:** AstraZeneca **Phone:** +1 302 885 1180 **Title:** Global Clinical Head ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.35 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Rate Ratio **Parameter Value:** 0.42 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.38 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.96 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Rate Ratio **Parameter Value:** 0.61 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.71 - **Spread:** - **Upper Limit:** 0.95 - **Value:** 0.82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.70 - **Spread:** - **Upper Limit:** 2.20 - **Value:** 1.93 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 0.76 - **Spread:** - **Upper Limit:** 1.51 - **Value:** 1.07 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 1.27 - **Spread:** - **Upper Limit:** 2.45 - **Value:** 1.76 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 49.62 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62.66 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47.15 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.97 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.14 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.55 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12.45 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.14 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17.99 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.64 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3.00 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.55 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.00 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 917.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 699.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 129.4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 100.0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **Title:** Annualized Asthma Exacerbation Rate (AAER) **Type:** SECONDARY **Unit of Measure:** events per year ##### Group **Description:** All subjects randomised to tezepelumab in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** OG000 **Title:** NAVIGATOR Rand Teze ##### Group **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **ID:** OG001 **Title:** NAVIGATOR Rand Pbo ##### Group **Description:** All subjects randomised to tezepelumab in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** OG002 **Title:** SOURCE Rand Teze ##### Group **Description:** All subjects randomised to placebo in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **ID:** OG003 **Title:** SOURCE Rand Pbo #### Outcome Measure 2 **Description:** Includes adverse events with an onset date between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set. Exposure adjusted rates are defined as number of subjects with AEs divided by total time at risk across all subjects, multiplied by 100 **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **Title:** Exposure Adjusted Incidence Rates of AEs/SAEs **Type:** PRIMARY **Unit of Measure:** Patients with AEs per 100 person-years ##### Group **Description:** All subjects randomised to tezepelumab in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** OG000 **Title:** NAVIGATOR Rand Teze ##### Group **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **ID:** OG001 **Title:** NAVIGATOR Rand Pbo ##### Group **Description:** All subjects randomised to tezepelumab in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** OG002 **Title:** SOURCE Rand Teze ##### Group **Description:** All subjects randomised to placebo in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **ID:** OG003 **Title:** SOURCE Rand Pbo #### Outcome Measure 3 **Description:** Includes time between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Baseline (Week 0 in predecessor study) to Week 104. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **Title:** Total Time at Risk **Type:** PRIMARY **Unit of Measure:** Year ##### Group **Description:** All subjects randomised to tezepelumab in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** OG000 **Title:** NAVIGATOR Rand Teze ##### Group **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **ID:** OG001 **Title:** NAVIGATOR Rand Pbo ##### Group **Description:** All subjects randomised to tezepelumab in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** OG002 **Title:** SOURCE Rand Teze ##### Group **Description:** All subjects randomised to placebo in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching treatments from placebo in the predecessor to tezepelumab in DESTINATION, all data collected after first dose of tezepelumab are excluded. **ID:** OG003 **Title:** SOURCE Rand Pbo ### Participant Flow Module #### Group **Description:** All subjects randomised to tezepelumab in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** FG000 **Title:** NAVIGATOR Rand Teze #### Group **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching to tezepelumab in DESTINATION, data collected during the placebo (predecessor) period are contained in this column, while data collected after the first dose of tezepelumab in DESTINATION are presented in the NAVIGATOR Pbo to Teze arm. **ID:** FG001 **Title:** NAVIGATOR Rand Pbo #### Group **Description:** All subjects randomised to placebo in the NAVIGATOR predecessor and re-randomised to tezepelumab in DESTINATION. Only data collected after the first dose of tezepelumab in DESTINATION are presented in this column. **ID:** FG002 **Title:** NAVIGATOR Pbo to Teze #### Group **Description:** All subjects randomised to tezepelumab in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. **ID:** FG003 **Title:** SOURCE Rand Teze #### Group **Description:** All subjects randomised to placebo in the SOURCE predecessor and treated with at least one dose in the predecessor, regardless of whether they participated in the DESTINATION study. For subjects switching to tezepelumab in DESTINATION, data collected during the placebo (predecessor) period are contained in this column, while data collected after the first dose of tezepelumab in DESTINATION are presented in the SOURCE Pbo to Teze arm. **ID:** FG004 **Title:** SOURCE Rand Pbo #### Group **Description:** All subjects randomised to placebo in the SOURCE predecessor and re-randomised to tezepelumab in DESTINATION. Only data collected after the first dose of tezepelumab in DESTINATION are presented in this column. **ID:** FG005 **Title:** SOURCE Pbo to Teze #### Period **Title:** Predecessor Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ###### Reason **Group ID:** FG001 **Number of Subjects:** 15 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 5 ###### Reason **Group ID:** FG004 **Number of Subjects:** 2 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Did not receive treatment / Non-compliance with protocol / did not complete safety follow-up visits ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 529 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 532 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 74 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 76 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** Received Treatment ###### Achievement **Group ID:** FG000 **Number of Subjects:** 528 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 531 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 74 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 76 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 513 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 509 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 68 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 73 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 16 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 23 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 0 #### Period **Title:** Long Term Extension (DESTINATION) ##### Withdraw **Type:** Due to COVID-19 pandemic ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 1 ##### Withdraw **Type:** Did not complete safety follow-up visits ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Pregnancy ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 3 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 415 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 206 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 206 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 60 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 32 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 32 ##### Milestone **Type:** Received Treatment ###### Achievement **Group ID:** FG000 **Number of Subjects:** 415 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 206 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 205 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 60 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 32 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 32 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 400 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 200 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 198 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 58 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 28 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 31 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 15 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 1 **Pre-Assignment Details:** Of the 1209 patients randomized and dosed in predecessor studies, 951 were randomised in DESTINATION and 950 received treatment. The patients receiving tezepelumab in the predecessors continued to receive tezepelumab, while patients receiving placebo in the predecessors were re-randomized 1:1 to either receive tezepelumab in DESTINATION or to continue placebo, resulting in a 3:1 randomization ratio in DESTINATION. **Recruitment Details:** Participants who completed treatment and attended end of treatment visit in predecessor studies NAVIGATOR (NCT03347279) or SOURCE (NCT03406078) were eligible for this long-term extension study. In the predecessor studies, a total of 1059 and 150 subjects were randomised and dosed in NAVIGATOR and SOURCE respectively. In DESTINATION, a total of 951 subjects (827 from NAVIGATOR and 124 from SOURCE) were randomised at 182 centres in 18 countries to receive treatment with tezepelumab or placebo. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01685879 **Brief Title:** Glycemic Response to High Amylose Rice **Official Title:** Glycemic Response to High Amylose Rice #### Organization Study ID Info **ID:** HARice #### Organization **Class:** OTHER **Full Name:** University of Hawaii #### Secondary ID Infos **Domain:** USDA **ID:** Project HAW00262H **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2014-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-09-01 **Type:** ESTIMATED **Last Update Submit Date:** 2014-08-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-10 **Type:** ACTUAL #### Start Date **Date:** 2012-10 **Status Verified Date:** 2014-08 #### Study First Post Date **Date:** 2012-09-14 **Type:** ESTIMATED **Study First Submit Date:** 2012-09-11 **Study First Submit QC Date:** 2012-09-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Hawaii #### Responsible Party **Investigator Affiliation:** University of Hawaii **Investigator Full Name:** Maria Stewart **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Certain types of rice have more dietary fiber than others. This type of rice is known a "high amylose rice." This study hypothesizes that high-amylose rice, will decrease blood glucose and insulin responses after consumption compared to conventional rice in healthy adults, ages 18-40. Eighteen healthy men and women will participate in this study. This study will determine how high blood glucose and insulin values rise after eating a portion of rice. This study will also evaluate hunger ratings after consuming rice. The results of this study will help researchers better understand how diet can influence diabetes management. **Detailed Description:** This is a pilot study to assess glucose response in humans to a rice sample prepared with high amylose rice (high amylose rice 1 and high amylose rice 2), compared to conventional rice and a glucose test beverage. Study Design: The proposed study is a randomized single-blind crossover design with repeated measures using human subjects (clinical study). Treatment: The amount of resistant starch, a type of dietary fiber, is greater for high amylose varieties of rice than conventional varieties of rice. High amylose rice is commercially produced in Louisiana and Arkansas, USA. This specific rice has been bred to contain more amylose than ordinary (conventional) rice. This food is not genetically modified. Brief Methods: Study subjects (men and women) aged 18-40 years old will be recruited from the UH-Manoa campus and Honolulu area via flyers. Interested individuals will be screened by telephone for initial eligibility (nonsmoker, non-vegetarian, habitual breakfast eater, able to fast for 12 hours, available 7:00am-10:00 am on weekdays, willing to participate in study). Based on the initial phone screening, eligible study subjects will attend an enrollment visit to complete the consent form, obtain study materials, and confirm health status and eligibility based on subject inclusion and exclusion criteria. Individuals who do not meet study eligibility will have all records destroyed. 18 healthy subjects (9 men and 9 women) will attend 4 morning study visits at the RMATRIX CRC at The Queens Medical Center. Subjects will complete a 24-hour food record for the 24 hours prior to the study visit. Subjects will be fasted for 12 hours at the time of the study visit. Upon arrival, subjects will have an IV inserted for serial blood draws, fasting blood samples will be obtained (time = 0). Subjects will then be presented one of four treatments in random order: high amylose rice-1, high amylose rice-2, conventional rice or glucose beverage. Subjects will be instructed to consume the sample or beverage within 15 minutes. Blood samples will be taken at 15, 30, 45, 60, 90, and 120 minutes. Subjects will complete an appetite survey after each blood draw. Upon completion of the study visit, subjects will be offered a snack and juice and monitored for safety. Study staff: A graduate research assistant in the Nutrition graduate program will coordinate the clinical study. Undergraduate research assistants will assist with study visits. All students will be working under Dr. Stewart's supervision. All study staff will complete UHM biosafety training, UMH blood borne pathogens training, and UMH or NIH human subjects training. Clinical Support: The study will be supported by nursing staff from the RMATRIX PCR to perform IV catheter insertion, collect serial blood samples and monitor for adverse events. ### Conditions Module **Conditions:** - Diabetes Treatment (Pilot Study) **Keywords:** - postprandial glycemic response - postprandial insulin response - rice - appetite - hunger ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 18 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Test rice with high dietary fiber content **Intervention Names:** - Other: Rice **Label:** High Amylose Rice 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Test rice with high dietary fiber content **Intervention Names:** - Other: Rice **Label:** High Amylose Rice 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Rice portion that contains 50 g carbohydrate. **Intervention Names:** - Other: Rice **Label:** Control Rice **Type:** PLACEBO_COMPARATOR #### Arm Group 4 **Description:** Glucose beverage with 50 g carbohydrate **Intervention Names:** - Other: Glucose Beverage **Label:** Glucose beverage **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - High Amylose Rice 1 **Description:** Rice portion containing 50 g total carbohydrate **Name:** Rice **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - High Amylose Rice 2 **Description:** Rice portion that provides 50 g total carbohydrate. **Name:** Rice **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Control Rice **Description:** Rice portion that provides 50 g total carbohydrate. **Name:** Rice **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Glucose beverage **Description:** Glucose beverage that provides 50 g total carbohydrate. **Name:** Glucose Beverage **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Evaluated changes in blood glucose after consuming a bolus of carbohydrate from rice or a standard glucose beverage. **Measure:** Blood Glucose response **Time Frame:** 120 minutes #### Secondary Outcomes **Description:** Measure insulin concentrations after consuming a bolus of carbohydrate from rice or standard glucose beverage. **Measure:** Insulin Response **Time Frame:** 120 minutes **Description:** Measure appetite after consuming a bolus of carbohydrate from rice or standard glucose beverage. **Measure:** Appetite Response **Time Frame:** 120 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Gender: male or female * Age 18-40 years old * In good general health * Habitual breakfast eater * Able to fast for 12 hours * Available 7:00am-9:30am on weekdays * Willing to participate in study and complete 4 study visits within a 6-week period * Capable of giving informed consent Exclusion Criteria: * Current smoker * BMI \> 30 kg/m2 * Current use of medications that alter appetite (antidepressants, antibiotics, weight loss medications, or appetite suppressants) * Current use of medications to control blood glucose, insulin or insulin receptors * History of pre-diabetes, diabetes, hyperglycemia, hyperinsulinemia, gastrointestinal disease or surgery, or eating disorders * Food allergy of any kind * Vegetarian * For females, pregnancy (current or within past 6 months) or lack of a regular menstrual cycle. * History of bleeding or clotting disorders (e.g. hemophilia, thrombocytopenia, Vitamin K deficiency, liver failure) * Current use of medications or supplements that may interfere with clotting and prolong bleeding time (e.g. aspirin, NSAIDS, coumadin, other anticoagulant therapy, herbal supplements including, but not limited to curcumin and flavonoids) * Problems with vascular access or difficulty tolerating blood draws **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Honolulu **Country:** United States **Facility:** University of Hawaii at Manoa **State:** Hawaii **Zip:** 96822 #### Overall Officials **Official 1:** **Affiliation:** University of Hawaii at Manoa **Name:** Maria Stewart, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02146079 **Brief Title:** A Trial to Assess the Pharmacokinetics, Pharmacodynamics, and the Safety and Tolerability of Semaglutide in Healthy Male Japanese and Caucasian Subjects **Official Title:** A Single-centre, Parallel-group, Randomised, Double-blind, Placebocontrolled, Multiple-dose Trial to Assess the Pharmacokinetics, Pharmacodynamics, and the Safety and Tolerability of Semaglutide in Healthy Male Japanese and Caucasian Subjects #### Organization Study ID Info **ID:** NN9535-3634 #### Organization **Class:** INDUSTRY **Full Name:** Novo Nordisk A/S #### Secondary ID Infos **Domain:** WHO **ID:** U1111-1147-6660 **Type:** OTHER **Domain:** JAPIC **ID:** JapicCTI-142550 **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2014-10-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-04-18 **Type:** ACTUAL **Last Update Submit Date:** 2018-04-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-10-20 **Type:** ACTUAL #### Start Date **Date:** 2014-05-21 **Type:** ACTUAL **Status Verified Date:** 2018-04 #### Study First Post Date **Date:** 2014-05-23 **Type:** ESTIMATED **Study First Submit Date:** 2014-05-21 **Study First Submit QC Date:** 2014-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novo Nordisk A/S #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This trial is conducted in Asia. The aim of the trial is to investigate the pharmacokinetics (the exposure of the trial drug in the body), pharmacodynamics (the effect of the investigated drug on the body), and the safety and tolerability of semaglutide in healthy male Japanese and Caucasian subjects. ### Conditions Module **Conditions:** - Diabetes - Diabetes Mellitus, Type 2 - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 44 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dose-escalation trial **Intervention Names:** - Drug: semaglutide **Label:** Semaglutide 0.5 mg **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: placebo **Label:** Semaglutide placebo 0.5 mg **Type:** PLACEBO_COMPARATOR #### Arm Group 3 **Description:** Dose-escalation trial **Intervention Names:** - Drug: semaglutide **Label:** Semaglutide 1.0 mg **Type:** EXPERIMENTAL #### Arm Group 4 **Intervention Names:** - Drug: placebo **Label:** Semaglutide placebo 1.0 mg **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Semaglutide 0.5 mg - Semaglutide 1.0 mg **Description:** Subjects will be randomised to receive either semaglutide 0.5 mg, semaglutide 0.5 mg placebo, semaglutide 1.0 mg or semaglutide 1.0 mg placebo within each group. Treatment with active drug or placebo blinded within each dose level. After randomisation, the subjects will follow a fixed dose escalation. The maintenance dose of 0.5 mg will be reached after 4 weeks of 0.25 mg. The maintenance dose of 1.0 mg will be reached after 8 weeks (4 weeks) of 0.25 mg and 4 weeks of 0.5 mg). Once-weekly subcutaneous (s.c., under the skin) administration. Trial duration per subject is 18 to 21 weeks depending on the individual subject's schedule **Name:** semaglutide **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Semaglutide placebo 0.5 mg - Semaglutide placebo 1.0 mg **Description:** Subjects will be randomised to receive either semaglutide 0.5 mg, semaglutide 0.5 mg placebo, semaglutide 1.0 mg or semaglutide 1.0 mg placebo within each group. Treatment with active drug or placebo blinded within each dose level. After randomisation, the subjects will follow a fixed dose escalation. The maintenance dose of 0.5 mg will be reached after 4 weeks of 0.25 mg. The maintenance dose of 1.0 mg will be reached after 8 weeks (4 weeks) of 0.25 mg and 4 weeks of 0.5 mg). Once-weekly subcutaneous (s.c., under the skin) administration. Trial duration per subject is 18 to 21 weeks depending on the individual subject's schedule. **Name:** placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Area under the plasma semaglutide concentration-time curve **Time Frame:** During a dosing interval (0-168 hours) at steady state #### Secondary Outcomes **Measure:** Maximum observed plasma semaglutide concentration at steady state **Time Frame:** 0-168 hours after the last dose of semaglutide (0.5 and 1.0 mg) **Measure:** Change in body weight from baseline to the end of treatment **Time Frame:** Day 1 of Visit 2 (2-21 days after Visit 1), Day 92 **Measure:** Number of treatment emergent adverse events (TEAEs) from baseline to follow-up **Time Frame:** From Day 1 of Visit 2 (2-21 days after Visit 1) to Day 120-127 (Visit 23) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy male Japanese and Caucasian subjects * Age between 20 and 55 years (both inclusive) at the time of signing informed consent * Body weight of equal to or above 54.0 kg * Body mass index (BMI) between 20.0 and 25.0 kg/m\^2 (both inclusive) * Glycosylated haemoglobin A1c (HbA1c) below or equal to 6.0% * For Japanese subjects only: both parents Japanese * For Caucasian subjects only: both parents Caucasian Exclusion Criteria: * Any clinically significant disease history, in the opinion of the investigator, or systemic or organ disease including: cardiological, pulmonary, gastrointestinal, hepatic, neurologic, renal, genitourinary and endocrine, dermatologic or hematologic diseases * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2) * History of chronic pancreatitis or idiopathic acute pancreatitis * Calcitonin above or equal to 50 ng/L * History of alcohol abuse within 1 year from screening, or a positive result in the alcohol breath test, or consumption of more than 21 units of alcohol weekly: 1 unit of alcohol equals approximately 250 mL of beer or lager, or approximately120 mL (one glass) of wine or Japanese sake, or approximately 20 mL of spirits * Smoking of more than 5 cigarettes (including nicotine substitute products) or the equivalent, per day or unwilling to refrain from smoking whenever required for the trial procedure * Use of prescription drugs within 3 weeks or 5 times the half-life, whichever is longer, prior to Visit 2 (randomisation), non-prescription drugs within 1 week prior to Visit 2 (randomisation). The use of vitamins, minerals and nutritional supplements, and the occasional use of paracetamol (acetaminophen) or acetylsalicylic acid are permitted **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 20 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tokyo **Country:** Japan **Facility:** Novo Nordisk Investigational Site **Zip:** 130-0004 #### Overall Officials **Official 1:** **Affiliation:** Novo Nordisk A/S **Name:** Global Clinical Registry (GCR, 1452) **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Ikushima I, Jensen L, Flint A, Nishida T, Zacho J, Irie S. A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects. Adv Ther. 2018 Apr;35(4):531-544. doi: 10.1007/s12325-018-0677-1. Epub 2018 Mar 13. **PMID:** 29536338 #### See Also Links **Label:** Clinical Trials at Novo Nordisk **URL:** http://novonordisk-trials.com ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Diabetes Mellitus, Type 2 - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Ancestors - ID: D000097789 - Term: Glucagon-Like Peptide-1 Receptor Agonists - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M353561 - Name: Semaglutide - Relevance: HIGH - As Found: Physical therapy - ID: M9043 - Name: Glucagon - Relevance: LOW - As Found: Unknown - ID: M3401 - Name: Glucagon-Like Peptide-1 Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M26997 - Name: Glucagon-Like Peptide 1 - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000591245 - Term: Semaglutide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03512379 **Brief Title:** Clinical Trial for the Application of Robotic System in Spinal Surgery **Official Title:** Clinical Trial for the Application of Robotic System in Spinal Surgery: a Randomized Controlled Study #### Organization Study ID Info **ID:** JST-201508 #### Organization **Class:** OTHER **Full Name:** Beijing Jishuitan Hospital ### Status Module #### Completion Date **Date:** 2021-12-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2018-09-24 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-20 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2015-08-01 **Type:** ACTUAL **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2018-04-30 **Type:** ACTUAL **Study First Submit Date:** 2018-04-03 **Study First Submit QC Date:** 2018-04-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Beijing Jishuitan Hospital #### Responsible Party **Investigator Affiliation:** Beijing Jishuitan Hospital **Investigator Full Name:** Wei Tian **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This randomized controlled study was designed to evaluate the accuracy, safety and clinical outcomes of the robot assisted spinal surgery. **Detailed Description:** Robot assisted operation is new for spinal surgery, in this study, we will evaluate the accuracy, safety and clinical outcomes compared with traditional free hand operation and navigation assisted operation. ### Conditions Module **Conditions:** - Robotic Surgical Procedures - Spinal Surgery - Safety **Keywords:** - robot-assisted surgery - pedicle screw - spine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Robot-assisted surgery group Free-hand surgery group Navigation-assisted surgery group ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1000 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Spinal surgery using TIANJI Robot system. **Intervention Names:** - Device: TIANJI Robot **Label:** Robot assisted surgery group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Spinal surgery using fluoroscopy-based free hand technique **Intervention Names:** - Device: Fluoroscopy **Label:** Free hand surgery group **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Spinal surgery using Navigation-assisted technique **Intervention Names:** - Device: Navigation **Label:** Navigation-assisted surgery group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Robot assisted surgery group **Description:** A robotic system for spinal surgery **Name:** TIANJI Robot **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Free hand surgery group **Description:** For fluoroscopy-based free hand surgery **Name:** Fluoroscopy **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Navigation-assisted surgery group **Description:** For navigation-assisted spinal surgery **Name:** Navigation **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The adjustment times of screw guide wire during surgery **Measure:** Screw guide wire adjustment times **Time Frame:** During surgery **Description:** The adjustment times of screw during surgery **Measure:** Screw adjustment times **Time Frame:** During surgery **Description:** The deviation between the actual position of screw and the preoperative designed position **Measure:** Deviation of screw **Time Frame:** Up to 12 weeks **Description:** Rate of screws breaching out pedicles on postoperative CT image **Measure:** Perforation rate of screw **Time Frame:** Up to 12 weeks #### Secondary Outcomes **Description:** Operation time **Measure:** Operation time **Time Frame:** During surgery **Description:** Blood loss during surgery **Measure:** Blood loss **Time Frame:** During surgery **Description:** Complications after surgery **Measure:** Complications **Time Frame:** Up to 4 weeks **Description:** Hospital stay after surgery **Measure:** Hospital stay after surgery **Time Frame:** Up to 4 weeks **Description:** Hospitalization costs **Measure:** Hospitalization costs **Time Frame:** Up to 4 weeks **Description:** Visual Analogue Scale **Measure:** Visual Analogue Scale **Time Frame:** 3 days before surgery **Description:** Visual Analogue Scale **Measure:** Visual Analogue Scale **Time Frame:** 3 days after surgery **Description:** Neck Disability Index **Measure:** Neck Disability Index **Time Frame:** 3 days before surgery **Description:** Neck Disability Index **Measure:** Neck Disability Index **Time Frame:** 3 days after surgery **Description:** Oswestry Disability Index **Measure:** Oswestry Disability Index **Time Frame:** 3 days before surgery **Description:** Oswestry Disability Index **Measure:** Oswestry Disability Index **Time Frame:** 3 days after surgery **Description:** modified Japanese orthopaedic association score **Measure:** modified Japanese orthopaedic association score **Time Frame:** 3 days before surgery **Description:** modified Japanese orthopaedic association score **Measure:** modified Japanese orthopaedic association score **Time Frame:** 3 days after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Spinal disease required for screw fixation；signed the inform consent Exclusion Criteria: * Patients with severe osteoporosis; patients with old fractures; patients with pedicle deformity; patients with severe systemic diseases; patients with coagulation disorders; patients who are considered unsuitable for this trail by the clinician. **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** van0208@163.com **Name:** Mingxing Fan, MD,PHD **Phone:** +86-13683360600 **Role:** CONTACT **Contact 2:** **Email:** drliuyajun@163.com **Name:** Yajun Liu, MD,PHD **Phone:** +86-13911878647 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** zhangweijun@tinavi.com - **Name:** Weijun Zhang, MD - **Phone:** 010-82156660 - **Role:** CONTACT **Country:** China **Facility:** Beijing Jishuitan Hospital **State:** Beijing **Status:** RECRUITING **Zip:** 100035 #### Overall Officials **Official 1:** **Affiliation:** Beijing Jishuitan Hospital **Name:** Wei Tian, MD,PHD **Role:** STUDY_CHAIR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00960479 **Brief Title:** Relative Bioavailability Study of Ribavirin 200 Capsules and Rebetol 200 mg Capsules in Females Under Fasting Conditions **Official Title:** A Relative Bioavailability Study of Ribavirin (Geneva Pharmaceutical Technology Corporation, N.J., U.S.A.) 200 Capsules and Rebetol (Schering Corporation, N.J., U.S.A.) 200 mg Capsules in Females Under Fasting Conditions. #### Organization Study ID Info **ID:** P1BH00001 #### Organization **Class:** INDUSTRY **Full Name:** Sandoz ### Status Module #### Completion Date **Date:** 2001-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-03-28 **Type:** ACTUAL **Last Update Submit Date:** 2017-03-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2001-02 **Type:** ACTUAL #### Start Date **Date:** 2001-01 **Status Verified Date:** 2009-08 #### Study First Post Date **Date:** 2009-08-17 **Type:** ESTIMATED **Study First Submit Date:** 2009-08-13 **Study First Submit QC Date:** 2009-08-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sandoz #### Responsible Party **Old Name Title:** Eric Mittleberg, Ph.D, VP of Product Development **Old Organization:** Sandoz Inc. ### Description Module **Brief Summary:** The purpose of this study is to demonstrate the relative bioavailability of Ribavirin 200 capsules and Rebetol 200 mg capsules in females under fasting conditions. ### Conditions Module **Conditions:** - Chronic Hepatitis C ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 38 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ribavirin 200 mg Oral Capsule (Geneva Pharmaceutical, U.S.A.) **Intervention Names:** - Drug: Ribavirin 200 mg Oral Capsule (Geneva Pharmaceutical, U.S.A.) **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Rebetol 200 mg Oral Capsule (Schering Corporation, U.S.A.) **Intervention Names:** - Drug: Rebetol 200 mg Oral Capsule (Schering Corporation, U.S.A.) **Label:** 2 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Name:** Ribavirin 200 mg Oral Capsule (Geneva Pharmaceutical, U.S.A.) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2 **Name:** Rebetol 200 mg Oral Capsule (Schering Corporation, U.S.A.) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Bioequivalence based on AUC and Cmax **Time Frame:** 30 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * No clinically significant abnormal finding on physical exam, medical history, or clinical laboratory results on screening. Exclusion Criteria: * Positive test results for HIV or hepatitis B or C. * Treatment for drug or alcohol dependence. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Allied Clinical Research **Name:** Piyush Patel, M.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006505 - Term: Hepatitis - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000014777 - Term: Virus Diseases - ID: D000018178 - Term: Flaviviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000006521 - Term: Hepatitis, Chronic - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9592 - Name: Hepatitis A - Relevance: LOW - As Found: Unknown - ID: M9591 - Name: Hepatitis - Relevance: LOW - As Found: Unknown - ID: M9607 - Name: Hepatitis, Chronic - Relevance: LOW - As Found: Unknown - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M21613 - Name: Hepatitis C, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis C - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006526 - Term: Hepatitis C - ID: D000019698 - Term: Hepatitis C, Chronic ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M15083 - Name: Ribavirin - Relevance: HIGH - As Found: Bevacizumab - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000012254 - Term: Ribavirin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00660179 **Acronym:** SERAPHIN **Brief Title:** Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension **Official Title:** A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Phase III Study to Assess the Effects of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension #### Organization Study ID Info **ID:** AC-055-302 #### Organization **Class:** INDUSTRY **Full Name:** Actelion ### Status Module #### Completion Date **Date:** 2012-04 **Type:** ACTUAL #### Disp First Post Date **Date:** 2012-10-29 **Type:** ESTIMATED **Disp First Submit Date:** 2012-10-23 **Disp First Submit QC Date:** 2012-10-23 #### Expanded Access Info #### Last Update Post Date **Date:** 2015-09-28 **Type:** ESTIMATED **Last Update Submit Date:** 2015-09-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-05-05 **Type:** ESTIMATED **Results First Submit Date:** 2013-11-05 **Results First Submit QC Date:** 2014-04-03 #### Start Date **Date:** 2008-05 **Status Verified Date:** 2015-08 #### Study First Post Date **Date:** 2008-04-17 **Type:** ESTIMATED **Study First Submit Date:** 2008-04-14 **Study First Submit QC Date:** 2008-04-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Actelion #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The AC-055-302/SERAPHIN study will be an event-driven Phase III study, comparing two different doses of macitentan (ACT-064992) (3 and 10 mg) vs placebo in patients with symptomatic PAH. The main study objective is to demonstrate that macitentan (ACT-064992) prolongs time to the first morbidity or mortality event, and to evaluate the benefit/risk profile of macitentan (ACT-064992) in the treatment of patients with symptomatic PAH. ### Conditions Module **Conditions:** - Pulmonary Arterial Hypertension **Keywords:** - pulmonary arterial hypertension SERAPHIN ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 742 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Macitentan (ACT-064992) tablet, 3 mg, once daily **Intervention Names:** - Drug: macitentan (ACT-064992) **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Macitentan (ACT-064992) tablet, 10 mg, once daily **Intervention Names:** - Drug: macitentan (ACT-064992) **Label:** 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Matching placebo, once daily **Intervention Names:** - Drug: placebo **Label:** 3 **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** Tablet, 3 mg dosage, once daily **Name:** macitentan (ACT-064992) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2 **Description:** Tablet, 10 mg dosage, once daily **Name:** macitentan (ACT-064992) **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - 3 **Description:** Matching placebo, once daily **Name:** placebo **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics **Measure:** Summary of the First Causes of Morbidity or Mortality **Time Frame:** Up to end of treatment (Up to 36 months) #### Primary Outcomes **Description:** Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics **Measure:** Time to First Confirmed Morbidity or Mortality Event up to the End of Treatment (Kaplan-Meier Estimate of Patients Without a Morbidity or Mortality Event) **Time Frame:** Up to end of treatment (data presented up to month 36) #### Secondary Outcomes **Description:** Events of PAH or hospitalization for PAH up to the end of treatment included: death due to PAH, or onset of a treatment-emergent adverse event with a fatal outcome due to PAH occurring up to 4 weeks after the end of treatment, or hospitalisation for PAH up to the end of treatment. **Measure:** Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event) **Time Frame:** Up to end of treatment (data presented up to month 36) **Description:** Events of death due to any cause up to the end of treatment (plus 7 days) **Measure:** Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event) **Time Frame:** Up to end of treatment (data presented up to month 36) **Description:** Events of death due to any cause up to the end of study (EOS). The initiation of EOS procedure occurred when the target of 285 events was expected to have been achieved (30 January 2012). **Measure:** Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event) **Time Frame:** Up to end of study (data presented up to month 36) **Description:** The 6-minute walk test (6MWT) is a non-encouraged test, performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. These guidelines were provided to all sites. For patients who had never performed a 6MWT previously, a training test was required before the qualifying tests for inclusion were performed. **Measure:** Change From Baseline to Month 6 in 6-minute Walk Distance **Time Frame:** Baseline to month 6 **Description:** Class I: no limitation of usual physical activity (PA) which does not increase dyspnea, fatigue, chest pain, or presyncope. Class II: mild limitation of PA. No discomfort at rest. Normal PA increases dyspnea, fatigue, chest pain, or presyncope. Class III: marked limitation of PA. No discomfort at rest. Less than ordinary activity increases dyspnea, fatigue, chest pain, or presyncope. Class IV: unable to perform any PA and who may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. **Measure:** Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6 **Time Frame:** Baseline to month 6 **Description:** In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period. **Measure:** Pulmonary Vascular Resistance at Baseline and Month 6 **Time Frame:** Baseline to month 6 **Description:** In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period. **Measure:** Cardiac Index at Baseline and Month 6 **Time Frame:** Baseline to month 6 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Signed informed consent prior to initiation of any study mandated procedure. 2. Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV. 3. Patients with the following types of pulmonary arterial hypertension (PAH) belonging to groups 1.1 to 1.3 of the Venice classification: * Idiopathic (IPAH); * Familial (FPAH); or * Related to: * Collagen vascular disease; * Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair; * Human immunodeficiency virus (HIV) infection; or * Drugs and toxins. 4. PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following: * Mean pulmonary artery pressure (mPAP) \> 25 mmHg at rest; * Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) \< 15 mmHg; and * Pulmonary vascular resistance (PVR) at rest \>= 320 dyn×sec/cm\^5. 5. 6-minute walk distance (6MWD) \>= 50 m. 6. Men or women \> 12 years of age (women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception). Exclusion Criteria: 1. PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher''s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy. 2. PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected. 3. PAH associated with significant venous or capillary involvement (PCWP \> 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis. 4. Persistent pulmonary hypertension of the newborn. 5. Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification. 6. Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 70% and FEV1 \< 65% of predicted value after bronchodilator administration. 7. Moderate to severe restrictive lung disease: total lung capacity (TLC) \< 60% of predicted value. 8. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C. 9. Estimated creatinine clearance \< 30 mL/min 10. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal. 11. Hemoglobin \< 75% of the lower limit of the normal range. 12. Systolic blood pressure \< 100 mmHg. 13. Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements. 14. Pregnant or breast-feeding. 15. Known concomitant life-threatening disease with a life expectancy \< 12 months. 16. Body weight \< 40 kg. 17. Any condition that prevents compliance with the protocol or adherence to therapy. 18. Recently started (\< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise. 19. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization. 20. Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors). 21. Treatment with cytochrome P3A (CYP3A) inducers within 4 weeks prior to randomization 22. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients. 23. Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization. **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** University of Alabama at Birmingham **State:** Alabama **Zip:** 35249-0001 **Location 2:** **City:** Pheonix **Country:** United States **Facility:** Arizona Pulmonary Specialists **State:** Arizona **Zip:** 85013 **Location 3:** **City:** Los Angeles **Country:** United States **Facility:** GLVA Healthcare Center **State:** California **Location 4:** **City:** San Diego **Country:** United States **Facility:** University of California, San Diego **State:** California **Location 5:** **City:** Santa Barbara **Country:** United States **Facility:** Santa Barbara Cottage Hospital **State:** California **Location 6:** **City:** Torrance **Country:** United States **Facility:** Liu Center for Pulmonary Hypertension **State:** California **Location 7:** **City:** Denver **Country:** United States **Facility:** University of Colorado Health Sciences Center **State:** Colorado **Location 8:** **City:** Jacksonville **Country:** United States **Facility:** Mayo Clinic, Jacksonville **State:** Florida **Location 9:** **City:** Atlanta **Country:** United States **Facility:** Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease **State:** Georgia **Zip:** 30322 **Location 10:** **City:** Atlanta **Country:** United States **Facility:** Pulmonary & Critical Care of Atlanta **State:** Georgia **Zip:** 30342 **Location 11:** **City:** Decatur **Country:** United States **Facility:** Southeastern Lung Care **State:** Georgia **Location 12:** **City:** Chicago **Country:** United States **Facility:** University of Chicago Hospitals **State:** Illinois **Location 13:** **City:** Iowa City **Country:** United States **Facility:** University of Iowa **State:** Iowa **Location 14:** **City:** Kansas City **Country:** United States **Facility:** University of Kansas Medical Center **State:** Kansas **Zip:** 66160 **Location 15:** **City:** Louisville **Country:** United States **Facility:** Kentuckiana Pulmonary Associate, PLLC **State:** Kentucky **Location 16:** **City:** New Orleans **Country:** United States **Facility:** Medical Center of Louisiana at New Orleans **State:** Louisiana **Location 17:** **City:** Portland **Country:** United States **Facility:** Maine Medical Center **State:** Maine **Zip:** 04102 **Location 18:** **City:** Baltimore **Country:** United States **Facility:** University of Maryland School of Medicine **State:** Maryland **Zip:** 21201 **Location 19:** **City:** Boston **Country:** United States **Facility:** Boston University School of Medicine **State:** Massachusetts **Location 20:** **City:** Boston **Country:** United States **Facility:** Pulmonary/Critical Care Division/Tufts New England Medical Center **State:** Massachusetts **Location 21:** **City:** Ann Arbor **Country:** United States **Facility:** University of Michigan **State:** Michigan **Location 22:** **City:** St. Louis **Country:** United States **Facility:** Washington University School of Medicine **State:** Missouri **Zip:** 63110 **Location 23:** **City:** New Brunswick **Country:** United States **Facility:** University of NJ - Robert Wood Johnson Medical School **State:** New Jersey **Location 24:** **City:** New York **Country:** United States **Facility:** Columbia University Medical Center - Pediatric Cardiology **State:** New York **Location 25:** **City:** Durham **Country:** United States **Facility:** Duke University Medical Center **State:** North Carolina **Location 26:** **City:** Cincinnati **Country:** United States **Facility:** University of Cincinnati Ohio Heart Health Center **State:** Ohio **Location 27:** **City:** Columbus **Country:** United States **Facility:** Ohio State University **State:** Ohio **Zip:** 43210 **Location 28:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University Medical Center **State:** Tennessee **Location 29:** **City:** Dallas **Country:** United States **Facility:** University of Texas Medical Center - St. Paul University **State:** Texas **Zip:** 75235 **Location 30:** **City:** Houston **Country:** United States **Facility:** Baylor College of Medicine and the Methodist Hospital **State:** Texas **Zip:** 77030 **Location 31:** **City:** Salt Lake City **Country:** United States **Facility:** Dept. of Pulmonary Medicine - Latter Day Saints Hospital **State:** Utah **Location 32:** **City:** Norfolk **Country:** United States **Facility:** Sentara Hospital T/A Sentara Cardiovascular Research Institute **State:** Virginia **Zip:** 23507 **Location 33:** **City:** Milwaukee **Country:** United States **Facility:** Comprehensive Cardiovascular Care Group **State:** Wisconsin **Location 34:** **City:** Buenos Aires **Country:** Argentina **Facility:** Fundacion Favaloro **Zip:** C1093AAS **Location 35:** **City:** Buenos Aires **Country:** Argentina **Facility:** Hospital Britanico **Location 36:** **City:** Buenos Aires **Country:** Argentina **Facility:** Sanatorio MITRE **Location 37:** **City:** Buenos Aires **Country:** Argentina **Facility:** SANATORIO OTAMENDI y MIROLI **Location 38:** **City:** Cordoba **Country:** Argentina **Facility:** Htal Italiano Cordoba **Location 39:** **City:** Cordoba **Country:** Argentina **Facility:** Htla privado de Cordoba **Location 40:** **City:** Corrientes **Country:** Argentina **Facility:** Instituto Cardiologia Corrientes **Location 41:** **City:** Santa Fe **Country:** Argentina **Facility:** 'Hospital Italiano - Garibaldi de Rosario **Location 42:** **City:** Darlinghurst, NSW **Country:** Australia **Facility:** St. Vincent's Hospital **Zip:** 2010 **Location 43:** **City:** Melbourne, VIC **Country:** Australia **Facility:** The Alfred Hospital **Zip:** 3181 **Location 44:** **City:** Sunshine Coast **Country:** Australia **Facility:** Royal Brisbane Hospital **Zip:** 4558 **Location 45:** **City:** Vienna **Country:** Austria **Facility:** Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology **Location 46:** **City:** Minsk **Country:** Belarus **Facility:** Republican reserach - Pratical Centre of Cardilogy **Zip:** 220036 **Location 47:** **City:** Minsk **Country:** Belarus **Facility:** Minsk Regional Clinical Hospital **Zip:** 223040 **Location 48:** **City:** Vitebsk **Country:** Belarus **Facility:** Vitebsk Regional Clinical Hospital **Zip:** 210037 **Location 49:** **City:** Leuven **Country:** Belgium **Facility:** University Hospital Gasthuisberg / Kliniekhoofd, Interne Geneeskunde - I.G. Pneumologie **Location 50:** **City:** Sofia **Country:** Bulgaria **Facility:** Specialized Hospital for Active Treatment of Cardio-Vascular Diseases / Department of Pediatric Cardiology **Zip:** 1309 **Location 51:** **City:** London **Country:** Canada **Facility:** London Health Sciences Centre / Victoria Hospital **State:** Ontario **Location 52:** **City:** Saint-Foy **Country:** Canada **Facility:** L'Hopital Laval **State:** Quebec **Location 53:** **City:** Calgary **Country:** Canada **Facility:** Peter Lougheed Centre **Location 54:** **City:** Toronto **Country:** Canada **Facility:** Toronto General Hospital **Location 55:** **City:** Vancouver **Country:** Canada **Facility:** Vancouver General Hospital **Zip:** V6Z 1Y6 **Location 56:** **City:** Santiago de Chile **Country:** Chile **Facility:** 'Pontificia Universidad Catolica de Chile **Location 57:** **City:** Santiago de Chile **Country:** Chile **Facility:** Hospital del Torax **Location 58:** **City:** Santiago **Country:** Chile **Facility:** Hospital San Juan de Dios **Location 59:** **City:** Guangzhou **Country:** China **Facility:** Guangdong General Hospital, Cardiology Department **State:** Guangdong **Zip:** 510080 **Location 60:** **City:** Nanjing **Country:** China **Facility:** Jiangsu Province Hospital - Pneumology Department **State:** Jiangsu **Zip:** 210029 **Location 61:** **City:** Beijing **Country:** China **Facility:** Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department **Zip:** 100029 **Location 62:** **City:** Beijing **Country:** China **Facility:** Peking Union Medcical College Hospital, Rheumatology Department **Zip:** 100032 **Location 63:** **City:** Beijing **Country:** China **Facility:** Chinese PLA General Hospital (301 Hospital), Cardiology Department **Zip:** 100853 **Location 64:** **City:** Shanghai **Country:** China **Facility:** Renji Hospital, Rheumatology Dept **Zip:** 200001 **Location 65:** **City:** Shanghai **Country:** China **Facility:** Zhongshan Hospital Fudan University, Cardiology Dept **Zip:** 200032 **Location 66:** **City:** Shanghai **Country:** China **Facility:** Renji Hospital, Cardiology Dept **Zip:** 200127 **Location 67:** **City:** Shanghai **Country:** China **Facility:** Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation **Zip:** 200433 **Location 68:** **City:** Bogota **Country:** Colombia **Facility:** Fundación Clínica Shaio **Location 69:** **City:** Floridablanca, Santander **Country:** Colombia **Facility:** 'Fundacion Cardiovascular de Colombia **Location 70:** **City:** Rijeka **Country:** Croatia **Facility:** Clinical Hospital Center **Zip:** 51 000 **Location 71:** **City:** Clamart **Country:** France **Facility:** Hôpital Antoine Béclère / Service de Pneumologie **Zip:** 92140 **Location 72:** **City:** Montpellier Cedex 5 **Country:** France **Facility:** Hôpital Arnaud de Villeneuve Service des Maladies Respiratoires **Zip:** 34295 **Location 73:** **City:** Pessac **Country:** France **Facility:** Hopital Haut-Leveque - Maison du Haut-Leveque **Zip:** 33604 **Location 74:** **City:** Berlin **Country:** Germany **Facility:** Unfallkrankenhaus Berlin, Klinik für Innere Medizin **Location 75:** **City:** Dresden **Country:** Germany **Facility:** Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus **Zip:** D-01307 **Location 76:** **City:** Giessen **Country:** Germany **Facility:** Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med. **Zip:** D-35392 **Location 77:** **City:** Greifswald **Country:** Germany **Facility:** Universität Greifswald / Klinik für Innere Medizin B, **Zip:** D-17487 **Location 78:** **City:** Hamburg **Country:** Germany **Facility:** Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie **Zip:** D-20246 **Location 79:** **City:** Heidelberg **Country:** Germany **Facility:** Thoraxklinik am Universitätsklinikum Heidelberg **Zip:** D-69126 **Location 80:** **City:** Homburg/Saar **Country:** Germany **Facility:** Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V **Zip:** D-66421 **Location 81:** **City:** Koln **Country:** Germany **Facility:** Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie **Zip:** D-50924 **Location 82:** **City:** Leipzig **Country:** Germany **Facility:** Universtätsklinik Leipzig **Zip:** 04103 **Location 83:** **City:** Mainz **Country:** Germany **Facility:** Klinikum der Johannes Gutenberg-Universität / II. Medizinische Klinik und Poliklinik **Zip:** D-55131 **Location 84:** **City:** Munich **Country:** Germany **Facility:** Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie **Zip:** D-81377 **Location 85:** **City:** Regensburg **Country:** Germany **Facility:** Universitätsklinikum Regensburg / Innere Medizin II **Zip:** 93053 **Location 86:** **City:** Hong Kong **Country:** Hong Kong **Facility:** Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics **Location 87:** **City:** Hong Kong **Country:** Hong Kong **Facility:** Queen Mary Hospital / Division of Cardiology, Department of Medicine **Location 88:** **City:** Budapest **Country:** Hungary **Facility:** Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology) **Zip:** H-1096 **Location 89:** **City:** Budapest **Country:** Hungary **Facility:** Semmelweis University, Pulmonolgy Clinic **Zip:** H-1125 **Location 90:** **City:** Szeged **Country:** Hungary **Facility:** University of Szeged Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of General Medicine, II. Internal Medicine Clinic, Cardiology Center **Location 91:** **City:** Ahmedabad **Country:** India **Facility:** Life Care Institute of Medical Science & Research, Ahmedabad **Zip:** 382428 **Location 92:** **City:** Delhi **Country:** India **Facility:** G B Pant Hospital & Maulana Azad Medical College **Zip:** 110049 **Location 93:** **City:** Hyderabad **Country:** India **Facility:** Care Hospital **Zip:** 500001 **Location 94:** **City:** Mumbai **Country:** India **Facility:** King Edward VII Memorial Hospital (KEM) Hospital **Zip:** 400 012 **Location 95:** **City:** Mumbai **Country:** India **Facility:** P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine **Zip:** 400016 **Location 96:** **City:** Pune **Country:** India **Facility:** Deenanath Mangeshkar Hospital and Research Centre **Zip:** 411 004 **Location 97:** **City:** Haifa **Country:** Israel **Facility:** Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division **Zip:** 34362 **Location 98:** **City:** Petach - Tikvah **Country:** Israel **Facility:** Rabin Medical Center - Belinson campus - Pulmonary Institute **Zip:** 49100 **Location 99:** **City:** Rehovot **Country:** Israel **Facility:** Pulmonary Institute, Kaplan Medical Center **Zip:** 76100 **Location 100:** **City:** Tel Hashomer **Country:** Israel **Facility:** The pulmonary institute Sheba Medical centre **Zip:** 52621 **Location 101:** **City:** Tel-Aviv **Country:** Israel **Facility:** Sourasky Medical Center - Division of Pulmonary Medicine and Allergy **Zip:** 64239 **Location 102:** **City:** Roma **Country:** Italy **Facility:** Policlinico Umberto I, Cardiologia **Zip:** 00161 **Location 103:** **City:** Kuala Lumpur **Country:** Malaysia **Facility:** Institut Jantung Negara (National Heart Institute) **Zip:** 50400 **Location 104:** **City:** Mexico City **Country:** Mexico **Facility:** 'Instituto Nacional de Cardiología (INC) Ignacio Chávez **Zip:** 14080 **Location 105:** **City:** Monterrey Nuevo León **Country:** Mexico **Facility:** Unidad de Investigación Clinica en Medicina, SC **Zip:** 64020 **Location 106:** **City:** Nieuwegein **Country:** Netherlands **Facility:** St. Antonius ziekenhuis **Zip:** 3435 CM **Location 107:** **City:** Oslo **Country:** Norway **Facility:** Aker University Dept of Cardilogy **Zip:** N0514 **Location 108:** **City:** Lima **Country:** Peru **Facility:** Hospital Alberto Sabogal Sologuren - EsSALUD **Location 109:** **City:** Lima **Country:** Peru **Facility:** IInstituto de Enfermedades Respiratorias, Clinica San Gabriel **Location 110:** **City:** Krakow **Country:** Poland **Facility:** Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ **Zip:** 31-202 **Location 111:** **City:** Warszawa **Country:** Poland **Facility:** Klinika Chorób Wewnętrznych Klatki Piersiowej **Zip:** 01-138 **Location 112:** **City:** Zabrze **Country:** Poland **Facility:** III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego **Zip:** 41-800 **Location 113:** **City:** Bucharest **Country:** Romania **Facility:** Institutul de boli cardiovasculare / Clinica de Cardiologie **Zip:** 022328 **Location 114:** **City:** Bucharest **Country:** Romania **Facility:** Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie **Zip:** 50159 **Location 115:** **City:** Ekaterinburg **Country:** Russian Federation **Facility:** Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department) **Zip:** 620102 **Location 116:** **City:** Kemerovo **Country:** Russian Federation **Facility:** Municipal Health Care Institution "Kemerovo Cardiology Dispensary" **Zip:** 650002 **Location 117:** **City:** Moscow **Country:** Russian Federation **Facility:** Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav" **Zip:** 105077 **Location 118:** **City:** Moscow **Country:** Russian Federation **Facility:** State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov" **Zip:** 117049 **Location 119:** **City:** Moscow **Country:** Russian Federation **Facility:** Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology" **Zip:** 121552 **Location 120:** **City:** St. Petersburg **Country:** Russian Federation **Facility:** Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology **Zip:** 194156 **Location 121:** **City:** St. Petersburg **Country:** Russian Federation **Facility:** State Educational Institution of High Professional Education **Zip:** 197 022 **Location 122:** **City:** Tomsk **Country:** Russian Federation **Facility:** State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch **Zip:** 634063 **Location 123:** **City:** Tomsk **Country:** Russian Federation **Facility:** Tomsk Regional Clinical Hospital / Pulmonology Unit **Zip:** 634063 **Location 124:** **City:** Yaroslavl **Country:** Russian Federation **Facility:** Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov" **Zip:** 150 003 **Location 125:** **City:** Belgrade **Country:** Serbia **Facility:** University Children's Hospital (UNIVERZITETSKA DEČJA KLINIKA) **Zip:** 11000 **Location 126:** **City:** Belgrade **Country:** Serbia **Facility:** University Clinical Center of Serbia / Institute for Lung Diseases and Tuberculosis **Zip:** 11000 **Location 127:** **City:** Belgrade **Country:** Serbia **Facility:** Zemun Clinical Hospital (Kliničko-bolnički centar "Zemun" ) / Department of Cardiology **Zip:** 11080 **Location 128:** **City:** Singapore **Country:** Singapore **Facility:** National University Hospital/ The Heart Institute **Zip:** 168752 **Location 129:** **City:** Singapore **Country:** Singapore **Facility:** Singapore General Hospital **Zip:** 168752 **Location 130:** **City:** Bratislava **Country:** Slovakia **Facility:** National Institute of Cardiovascular Diseases (Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH) / Department of Heart Transplantation **Zip:** 833 48 **Location 131:** **City:** Bratislava **Country:** Slovakia **Facility:** Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií), Department of Cardiology and Angiology **Zip:** 833 48 **Location 132:** **City:** Johannesburg **Country:** South Africa **Facility:** Netcare Milpark Hospital,Center for Chest Disease **Zip:** 2000 **Location 133:** **City:** Johannesburg **Country:** South Africa **Facility:** Chris Hani Baragwanath Hospital, Department of Cardiology **Zip:** 27-11-033 8197 **Location 134:** **City:** Parow **Country:** South Africa **Facility:** Tread Research **Zip:** 7505 **Location 135:** **City:** Somerset West **Country:** South Africa **Facility:** Block 4, Vergelegen Medi-Clinic **Zip:** 7130 **Location 136:** **City:** A Coruna **Country:** Spain **Facility:** Hospital Juan Canalejo Servicio de Neumología **Zip:** 15006 **Location 137:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Universitario Vall d'Hebron, Pneumology Unit, Planta Baja Hospital General **Zip:** 08035 **Location 138:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Clínico I Provincial, Servicio de Neumología. **Zip:** 08036 **Location 139:** **City:** Madrid **Country:** Spain **Facility:** Hospital 12 Octubre/ Cardiology department Planta 5a. **Zip:** 20841 **Location 140:** **City:** Malaga **Country:** Spain **Facility:** Hospital Clínico Virgen de la Victoria / Pneumology Unit, **Zip:** 29010 **Location 141:** **City:** Pontevedra **Country:** Spain **Facility:** Hospital Montecelo, Servicio de Neumología **Zip:** 36771 **Location 142:** **City:** Lund **Country:** Sweden **Facility:** University Hospital in Lund, Heart and Lung Division **Zip:** SE-221 85 **Location 143:** **City:** Uppsala **Country:** Sweden **Facility:** Servicio de Medicina Interna, Unidad de Hipertensión Pulmonar **Zip:** 751 85 **Location 144:** **City:** Taichung **Country:** Taiwan **Facility:** Taichung Veterans General Hospital / Division of Allergy, Immunology and Rheumatology **Zip:** 40705 **Location 145:** **City:** Taipei **Country:** Taiwan **Facility:** National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department **Location 146:** **City:** Bangkok **Country:** Thailand **Facility:** Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine, **Zip:** 10400 **Location 147:** **City:** Bangkok **Country:** Thailand **Facility:** Siriraj Hospital/ Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University **Zip:** 10700 **Location 148:** **City:** Chiang Mai **Country:** Thailand **Facility:** Chiang Mai Hospital / Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University **Location 149:** **City:** Khon Kaen **Country:** Thailand **Facility:** Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University **Zip:** 40002 **Location 150:** **City:** Istanbul **Country:** Turkey **Facility:** Istanbul University Cardiology Institure **Location 151:** **City:** Dnepropetrovsk **Country:** Ukraine **Facility:** Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid **Zip:** 49060 **Location 152:** **City:** Lviv **Country:** Ukraine **Facility:** Danylo Halytskyi Lviv State Medical University **Zip:** 79010 **Location 153:** **City:** London **Country:** United Kingdom **Facility:** Royal Free Hospital **Zip:** NW3 2QG #### Overall Officials **Official 1:** **Affiliation:** Actelion **Name:** Loic Perchenet, PhD **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L, Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013 Aug 29;369(9):809-18. doi: 10.1056/NEJMoa1213917. **PMID:** 23984728 **Citation:** Di Scala L, Bacchi M, Bayer B, Turricchia S. Adjusting Overall Survival Estimates of Macitentan in Pulmonary Arterial Hypertension After Treatment Switching: Results from the SERAPHIN Study. Adv Ther. 2022 Sep;39(9):4346-4358. doi: 10.1007/s12325-022-02253-8. Epub 2022 Aug 1. **PMID:** 35917059 **Citation:** Souza R, Delcroix M, Galie N, Jansa P, Mehta S, Pulido T, Rubin L, Sastry BKS, Simonneau G, Sitbon O, Torbicki A, Boyanova N, Chamitava L, Stein C, Channick RN. Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension. Adv Ther. 2022 Sep;39(9):4374-4390. doi: 10.1007/s12325-022-02199-x. Epub 2022 Jul 12. **PMID:** 35819570 **Citation:** Torbicki A, Bacchi M, Delcroix M, Farber HW, Ghofrani HA, Hennessy B, Jansa P, Mehta S, Perchenet L, Pulido T, Rosenberg D, Rubin LJ, Sastry BKS, Simonneau G, Sitbon O, Souza R, Wei LJ, Channick R, Benza R. Integrating Data From Randomized Controlled Trials and Observational Studies to Assess Survival in Rare Diseases. Circ Cardiovasc Qual Outcomes. 2019 May;12(5):e005095. doi: 10.1161/CIRCOUTCOMES.118.005095. **PMID:** 31109190 **Citation:** Krause A, Zisowsky J, Dingemanse J. Modeling of pharmacokinetics, efficacy, and hemodynamic effects of macitentan in patients with pulmonary arterial hypertension. Pulm Pharmacol Ther. 2018 Apr;49:140-146. doi: 10.1016/j.pupt.2018.02.005. Epub 2018 Feb 28. **PMID:** 29501590 **Citation:** McLaughlin VV, Hoeper MM, Channick RN, Chin KM, Delcroix M, Gaine S, Ghofrani HA, Jansa P, Lang IM, Mehta S, Pulido T, Sastry BKS, Simonneau G, Sitbon O, Souza R, Torbicki A, Tapson VF, Perchenet L, Preiss R, Verweij P, Rubin LJ, Galie N. Pulmonary Arterial Hypertension-Related Morbidity Is Prognostic for Mortality. J Am Coll Cardiol. 2018 Feb 20;71(7):752-763. doi: 10.1016/j.jacc.2017.12.010. **PMID:** 29447737 **Citation:** Jansa P, Pulido T. Macitentan in Pulmonary Arterial Hypertension: A Focus on Combination Therapy in the SERAPHIN Trial. Am J Cardiovasc Drugs. 2018 Feb;18(1):1-11. doi: 10.1007/s40256-017-0260-1. **PMID:** 29280064 **Citation:** Mehta S, Sastry BKS, Souza R, Torbicki A, Ghofrani HA, Channick RN, Delcroix M, Pulido T, Simonneau G, Wlodarczyk J, Rubin LJ, Jansa P, Hunsche E, Galie N, Perchenet L, Sitbon O. Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial. Chest. 2017 Jan;151(1):106-118. doi: 10.1016/j.chest.2016.08.1473. Epub 2016 Sep 23. Erratum In: Chest. 2018 May;153(5):1287. **PMID:** 27671974 **Citation:** Simonneau G, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Le Brun FO, Mehta S, Perchenet L, Pulido T, Sastry BK, Sitbon O, Souza R, Torbicki A, Rubin LJ. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J. 2015 Dec;46(6):1711-20. doi: 10.1183/13993003.00364-2015. Epub 2015 Oct 22. **PMID:** 26493786 **Citation:** Channick RN, Delcroix M, Ghofrani HA, Hunsche E, Jansa P, Le Brun FO, Mehta S, Pulido T, Rubin LJ, Sastry BKS, Simonneau G, Sitbon O, Souza R, Torbicki A, Galie N. Effect of macitentan on hospitalizations: results from the SERAPHIN trial. JACC Heart Fail. 2015 Jan;3(1):1-8. doi: 10.1016/j.jchf.2014.07.013. Epub 2014 Nov 11. **PMID:** 25457902 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006976 - Term: Hypertension, Pulmonary - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M2261 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - ID: M10027 - Name: Hypertension, Pulmonary - Relevance: LOW - As Found: Unknown - ID: M30541 - Name: Familial Primary Pulmonary Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T4807 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension ### Condition Browse Module - Meshes - ID: D000081029 - Term: Pulmonary Arterial Hypertension - ID: D000065627 - Term: Familial Primary Pulmonary Hypertension - ID: D000006973 - Term: Hypertension ### Intervention Browse Module - Ancestors - ID: D000065130 - Term: Endothelin A Receptor Antagonists - ID: D000065128 - Term: Endothelin Receptor Antagonists - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000065131 - Term: Endothelin B Receptor Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M258148 - Name: Macitentan - Relevance: HIGH - As Found: Humira - ID: M30468 - Name: Endothelin A Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M30466 - Name: Endothelin Receptor Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000533860 - Term: Macitentan ### Misc Info Module #### Removed Countries - Country: Brazil - Country: Czech Republic - Country: Denmark - Country: Finland - Country: Former Serbia and Montenegro - Country: Portugal - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** One patient in the placebo group never received study treatment and was not included in the analysis. Adverse events during treatment period and up to 28 days after treatment discontinuation #### Event Groups **Group ID:** EG000 **Title:** Placebo **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** EG000 **Other Num Affected:** 219 **Other Num at Risk:** 249 **Serious Number Affected:** 137 **Serious Number At Risk:** 249 **Title:** Placebo **Group ID:** EG001 **Title:** ACT-064992 3 mg **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** EG001 **Other Num Affected:** 227 **Other Num at Risk:** 250 **Serious Number Affected:** 130 **Serious Number At Risk:** 250 **Title:** ACT-064992 3 mg **Group ID:** EG002 **Title:** ACT-064992 10 mg **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** EG002 **Other Num Affected:** 222 **Other Num at Risk:** 242 **Serious Number Affected:** 109 **Serious Number At Risk:** 242 **Title:** ACT-064992 10 mg **Frequency Threshold:** 5 #### Other Events **Term:** UPPER RESPIRATORY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** OEDEMA PERIPHERAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 **Term:** NASOPHARYNGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** HEADACHE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 **Term:** PULMONARY ARTERIAL HYPERTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** DIZZINESS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 **Term:** ANAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 **Term:** BRONCHITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** COUGH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** DYSPNOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** CHEST PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 **Term:** DIARRHOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** URINARY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** INSOMNIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.0 **Term:** HYPOKALAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 **Term:** HYPOTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 **Term:** RIGHT VENTRICULAR FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 **Term:** ARTHRALGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 **Term:** PHARYNGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** PALPITATIONS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 **Term:** INFLUENZA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** BACK PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 **Term:** NAUSEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** RESPIRATORY TRACT INFECTION VIRAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 **Term:** SYNCOPE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 **Term:** FATIGUE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 **Term:** VOMITING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** DYSPEPSIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 **Term:** PAIN IN EXTREMITY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 #### Serious Events **Term:** PULMONARY ARTERIAL HYPERTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 56 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 48 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 32 **Num At Risk:** 242 **Term:** HAEMOPTYSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 3 **Num At Risk:** 242 **Term:** RESPIRATORY FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 3 **Num At Risk:** 242 **Term:** DYSPNOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** PULMONARY EMBOLISM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** CHRONIC OBSTRUCTIVE PULMONARY DISEASE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ACUTE RESPIRATORY FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** EPISTAXIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PULMONARY FIBROSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PLEURAL EFFUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HYPOXIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** INTERSTITIAL LUNG DISEASE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LUNG INFILTRATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PHARYNGEAL CYST **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PLEURITIC PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PNEUMONIA ASPIRATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TACHYPNOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PNEUMOTHORAX **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SLEEP APNOEA SYNDROME **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RIGHT VENTRICULAR FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 40 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 21 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 23 **Num At Risk:** 242 **Term:** ATRIAL FLUTTER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 4 **Num At Risk:** 242 **Term:** CARDIAC ARREST **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SUPRAVENTRICULAR TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** ACUTE MYOCARDIAL INFARCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ATRIAL TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** BRADYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** CARDIO-RESPIRATORY ARREST **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ATRIAL FIBRILLATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LEFT VENTRICULAR FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ACUTE RIGHT VENTRICULAR FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ANGINA PECTORIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CARDIOGENIC SHOCK **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** CORONARY ARTERY DISEASE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ARRHYTHMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ATRIOVENTRICULAR BLOCK **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ATRIOVENTRICULAR BLOCK COMPLETE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PALPITATIONS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RIGHT VENTRICULAR DYSFUNCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** VENTRICULAR TACHYCARDIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ACUTE CORONARY SYNDROME **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ACUTE LEFT VENTRICULAR FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CARDIAC FAILURE CONGESTIVE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CARDIOPULMONARY FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LEFT VENTRICULAR DYSFUNCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PERICARDIAL EFFUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TACHYARRHYTHMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PNEUMONIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 8 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 4 **Num At Risk:** 242 **Term:** GASTROENTERITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** BRONCHITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** UPPER RESPIRATORY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** URINARY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** RESPIRATORY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** LOWER RESPIRATORY TRACT INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ERYSIPELAS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SEPSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** LUNG INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SEPTIC SHOCK **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** WOUND INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** BACTERIAL SEPSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** BRONCHITIS BACTERIAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** DENGUE FEVER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DIARRHOEA INFECTIOUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ENTEROCOCCAL SEPSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HEPATITIS E **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LOBAR PNEUMONIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LUNG INFECTION PSEUDOMONAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** NASOPHARYNGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OMPHALITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** OVERGROWTH BACTERIAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PAROTID ABSCESS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PNEUMONIA INFLUENZAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PNEUMONIA MORAXELLA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PNEUMONIA NECROTISING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PNEUMONIA PNEUMOCOCCAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** POST PROCEDURAL CELLULITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PYELONEPHRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** SALPINGO-OOPHORITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** SIALOADENITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** TRACHEOBRONCHITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** VIRAL INFECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** VULVAL ABSCESS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** CELLULITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ABSCESS INTESTINAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** APPENDICITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CUTANEOUS TUBERCULOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HERPES ZOSTER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** INFECTED SKIN ULCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SINUSITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PANCREATITIS ACUTE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** UPPER GASTROINTESTINAL HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DIARRHOEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** GASTRIC ULCER HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HAEMATEMESIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ASCITES **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ABDOMINAL DISTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ABDOMINAL PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ANAL POLYP **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** COLITIS ISCHAEMIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DYSPHAGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** GASTROINTESTINAL MOTILITY DISORDER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** GINGIVAL BLEEDING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** INTESTINAL OBSTRUCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** MALABSORPTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** NAUSEA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OESOPHAGEAL VARICES HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PANCREATITIS RELAPSING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PEPTIC ULCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** TONGUE HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** VOMITING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ILEUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** INGUINAL HERNIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PANCREATIC MASS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PERITONITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RECTAL HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CHEST PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 3 **Num At Risk:** 242 **Term:** SUDDEN DEATH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** SUDDEN CARDIAC DEATH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** GENERAL PHYSICAL HEALTH DETERIORATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** PYREXIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ADVERSE DRUG REACTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DEATH **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** CHEST DISCOMFORT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DEVICE MALFUNCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** FATIGUE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** MULTI-ORGAN DISORDER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** MULTI-ORGAN FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** DEVICE DISLOCATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OEDEMA PERIPHERAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SYNCOPE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 4 **Num At Risk:** 242 **Term:** CARPAL TUNNEL SYNDROME **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HEADACHE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ISCHAEMIC STROKE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** SCIATICA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SUBARACHNOID HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PRESYNCOPE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CEREBRAL INFARCTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CEREBROVASCULAR ACCIDENT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TRIGEMINAL NEURALGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ANAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 6 **Num At Risk:** 242 **Term:** THROMBOCYTOPENIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** COAGULOPATHY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HAEMOLYTIC ANAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HAEMORRHAGIC ANAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HYPOCOAGULABLE STATE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ANAEMIA MEGALOBLASTIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** COLON CANCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OVARIAN NEOPLASM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** UTERINE LEIOMYOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** BREAST CANCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ANGIOSARCOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** METASTATIC NEOPLASM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RECTOSIGMOID CANCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TONGUE NEOPLASM BENIGN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RECTAL CANCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** MENORRHAGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** DYSFUNCTIONAL UTERINE BLEEDING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OVARIAN CYST **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** METRORRHAGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PELVIC FLUID COLLECTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** POSTMENOPAUSAL HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** VAGINAL HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** UTERINE HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ALANINE AMINOTRANSFERASE INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** ASPARTATE AMINOTRANSFERASE INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** LIVER FUNCTION TEST ABNORMAL **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** HEPATIC ENZYME INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HAEMOGLOBIN DECREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HEPATITIS B VIRUS TEST POSITIVE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HIV TEST POSITIVE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** INTERNATIONAL NORMALISED RATIO DECREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TRANSAMINASES INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** GAMMA-GLUTAMYLTRANSFERASE INCREASED **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SUBDURAL HAEMATOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ANKLE FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** FEMUR FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LUMBAR VERTEBRAL FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ROAD TRAFFIC ACCIDENT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** THORACIC VERTEBRAL FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** UPPER LIMB FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** BRAIN CONTUSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** BRAIN HERNIATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PATELLA FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** POST PROCEDURAL HAEMORRHAGE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SKULL FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TRAUMATIC BRAIN INJURY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SYSTEMIC LUPUS ERYTHEMATOSUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** SYSTEMIC SCLEROSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 242 **Term:** BACK PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OSTEOARTHRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** COSTOCHONDRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** MUSCULOSKELETAL PAIN **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ARTHRALGIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** OSTEOPOROTIC FRACTURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PAIN IN EXTREMITY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RENAL FAILURE ACUTE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** GLOMERULONEPHRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** LUPUS NEPHRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** NEPHROLITHIASIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RENAL IMPAIRMENT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TUBULOINTERSTITIAL NEPHRITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CALCULUS URINARY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PROTEINURIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RENAL COLIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** RENAL FAILURE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CHOLECYSTITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** CHOLELITHIASIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HEPATITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** JAUNDICE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** BILIARY COLIC **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CHOLANGITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ISCHAEMIC HEPATITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LIVER INJURY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HEPATIC CIRRHOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** POST CHOLECYSTECTOMY SYNDROME **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PREGNANCY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Pregnancy, puerperium and perinatal conditions **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** COMPLICATION OF PREGNANCY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Pregnancy, puerperium and perinatal conditions **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HYPOTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** HYPOVOLAEMIC SHOCK **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ARTERIOVENOUS FISTULA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ORTHOSTATIC HYPOTENSION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ARTERIAL THROMBOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CIRCULATORY COLLAPSE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HYPERTENSIVE CRISIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** VASCULITIS NECROTISING **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DEHYDRATION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HYPONATRAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ELECTROLYTE IMBALANCE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** FLUID OVERLOAD **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HYPERGLYCAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HYPOGLYCAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DIABETES MELLITUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DIABETIC KETOACIDOSIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** GOUT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HYPERURICAEMIA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TYPE 2 DIABETES MELLITUS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** CONFUSIONAL STATE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ALCOHOLISM **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** MENTAL DISORDER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** MENTAL STATUS CHANGES **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** DRUG ABUSE **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** SKIN ULCER **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** ECZEMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** LEUKOCYTOCLASTIC VASCULITIS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** PURPURA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HIP ARTHROPLASTY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** CARDIAC PACEMAKER INSERTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** HEART AND LUNG TRANSPLANT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** TOOTH EXTRACTION **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** GLYCOGEN STORAGE DISEASE TYPE V **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 250 **Group ID:** EG002 **Num At Risk:** 242 **Term:** ADRENAL INSUFFICIENCY **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Term:** GLAUCOMA **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 14.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 249 **Group ID:** EG001 **Num At Risk:** 250 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 242 **Time Frame:** Up to end of treatment plus 28 days (Up to approximately 36 months) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 250 **Group ID:** BG001 **Value:** 250 **Group ID:** BG002 **Value:** 242 **Group ID:** BG003 **Value:** 742 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo **Description:** Matching ACT-064992 placebo tablet, once daily ### Group **ID:** BG001 **Title:** ACT-064992 3 mg **Description:** ACT-064992 tablet, 3 mg, once daily ### Group **ID:** BG002 **Title:** ACT-064992 10 mg **Description:** ACT-064992 tablet, 10 mg, once daily ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 20 **Class Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 199 #### Measurement **Group ID:** BG001 **Value:** 208 #### Measurement **Group ID:** BG002 **Value:** 209 #### Measurement **Group ID:** BG003 **Value:** 616 **Class Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 43 #### Measurement **Group ID:** BG001 **Value:** 33 #### Measurement **Group ID:** BG002 **Value:** 27 #### Measurement **Group ID:** BG003 **Value:** 103 **Class Title:** >=65 years ### Measure #### Measurement **Group ID:** BG000 **Spread:** 17.03 **Value:** 46.7 #### Measurement **Group ID:** BG001 **Spread:** 16.26 **Value:** 44.5 #### Measurement **Group ID:** BG002 **Spread:** 14.99 **Value:** 45.5 #### Measurement **Group ID:** BG003 **Spread:** 16.13 **Value:** 45.6 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 184 #### Measurement **Group ID:** BG001 **Value:** 187 #### Measurement **Group ID:** BG002 **Value:** 194 #### Measurement **Group ID:** BG003 **Value:** 565 **Class Title:** Female #### Measurement **Group ID:** BG000 **Value:** 65 #### Measurement **Group ID:** BG001 **Value:** 61 #### Measurement **Group ID:** BG002 **Value:** 48 #### Measurement **Group ID:** BG003 **Value:** 174 **Class Title:** Male ### Measure #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 13 #### Measurement **Group ID:** BG003 **Value:** 43 **Class Title:** Argentina #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 10 **Class Title:** Australia #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 4 **Class Title:** Austria #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 8 #### Measurement **Group ID:** BG003 **Value:** 23 **Class Title:** Belarus #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 2 **Class Title:** Belgium #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 6 **Class Title:** Bulgaria #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 16 **Class Title:** Canada #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 9 #### Measurement **Group ID:** BG003 **Value:** 28 **Class Title:** Chile #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 29 #### Measurement **Group ID:** BG002 **Value:** 27 #### Measurement **Group ID:** BG003 **Value:** 87 **Class Title:** China #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 9 **Class Title:** Colombia #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 1 **Class Title:** Croatia #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 **Class Title:** Denmark #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 11 **Class Title:** France #### Measurement **Group ID:** BG000 **Value:** 17 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 13 #### Measurement **Group ID:** BG003 **Value:** 44 **Class Title:** Germany #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 4 **Class Title:** Hong Kong #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 6 **Class Title:** Hungary #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 17 #### Measurement **Group ID:** BG002 **Value:** 15 #### Measurement **Group ID:** BG003 **Value:** 47 **Class Title:** India #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 8 #### Measurement **Group ID:** BG003 **Value:** 20 **Class Title:** Israel #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 5 **Class Title:** Italy #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 7 **Class Title:** Malaysia #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 13 #### Measurement **Group ID:** BG002 **Value:** 14 #### Measurement **Group ID:** BG003 **Value:** 40 **Class Title:** Mexico #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 **Class Title:** Netherlands #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 2 **Class Title:** Norway #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 7 **Class Title:** Peru #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 7 #### Measurement **Group ID:** BG003 **Value:** 21 **Class Title:** Poland #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 16 **Class Title:** Romania #### Measurement **Group ID:** BG000 **Value:** 25 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 23 #### Measurement **Group ID:** BG003 **Value:** 72 **Class Title:** Russian Federation #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 16 **Class Title:** Serbia #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 13 **Class Title:** Singapore #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 6 **Class Title:** Slovakia #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 8 #### Measurement **Group ID:** BG003 **Value:** 24 **Class Title:** South Africa #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 15 **Class Title:** Spain #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 7 **Class Title:** Sweden #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 14 **Class Title:** Taiwan #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 9 #### Measurement **Group ID:** BG003 **Value:** 25 **Class Title:** Thailand #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 3 **Class Title:** Turkey #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 5 **Class Title:** United Kingdom #### Measurement **Group ID:** BG000 **Value:** 23 #### Measurement **Group ID:** BG001 **Value:** 25 #### Measurement **Group ID:** BG002 **Value:** 19 #### Measurement **Group ID:** BG003 **Value:** 67 **Class Title:** United States #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 14 **Class Title:** Ukraine ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 1 **Class Title:** Class I #### Measurement **Group ID:** BG000 **Value:** 129 #### Measurement **Group ID:** BG001 **Value:** 138 #### Measurement **Group ID:** BG002 **Value:** 120 #### Measurement **Group ID:** BG003 **Value:** 387 **Class Title:** Class II #### Measurement **Group ID:** BG000 **Value:** 116 #### Measurement **Group ID:** BG001 **Value:** 105 #### Measurement **Group ID:** BG002 **Value:** 116 #### Measurement **Group ID:** BG003 **Value:** 337 **Class Title:** Class III #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 14 **Class Title:** Class IV **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** NUMBER **Title:** Age, Categorical **Unit of Measure:** participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** NUMBER **Title:** Gender **Unit of Measure:** participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 5 **Description:** Class I: no limitation of usual physical activity (PA) which does not increase dyspnea, fatigue, chest pain, or presyncope. Class II: mild limitation of PA. No discomfort at rest. Normal PA increases dyspnea, fatigue, chest pain, or presyncope. Class III: marked limitation of PA. No discomfort at rest. Less than ordinary activity increases dyspnea, fatigue, chest pain, or presyncope. Class IV: unable to perform any PA and who may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. **Parameter Type:** NUMBER **Title:** World Health Organisation Functional Class **Unit of Measure:** participants **Population Description:** For the baseline measures of age, gender, and World Health Organization (WHO) functional class, data were missing for 1 patient in the placebo group and for 2 patients in the 3 mg macitentan group. ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Point of Contact **Email:** parisa.danaietash@actelion.com **Organization:** Actelion Pharmaceuticals Ltd **Title:** Parisa Danaietash ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.516 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 0.960 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0108 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.704 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.392 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 0.762 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.547 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 0.462 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 0.970 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0146 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.669 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.335 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 0.747 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.500 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 0.477 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 1.976 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.9249 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.971 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.287 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 1.418 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2037 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.638 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False ### Outcome Measure 4 #### Analysis **CI Lower Limit:** 0.653 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 1.673 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8312 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 1.046 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.464 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 97.5 **CI Upper Limit:** 1.282 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2509 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.771 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** False ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 92.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 81.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 65.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 55.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 63.2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 76.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 78.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 81.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 55.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70.6 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 95.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 97.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 97.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 95.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 96.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 92.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 87.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93.3 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 96.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 96.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 95.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 87.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 87.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 83.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 86.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82.9 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 110.6 - **Upper Limit:** - **Value:** 352 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 95.5 - **Upper Limit:** - **Value:** 364 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 93.2 - **Upper Limit:** - **Value:** 363 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 100.59 - **Upper Limit:** - **Value:** -9.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 93.15 - **Upper Limit:** - **Value:** 7.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 83.54 - **Upper Limit:** - **Value:** 12.5 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 49 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 54 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 259 - **Spread:** 587 - **Upper Limit:** 3390 - **Value:** 886 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 250 - **Spread:** 541 - **Upper Limit:** 2317 - **Value:** 945 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 254 - **Spread:** 550 - **Upper Limit:** 2279 - **Value:** 907 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 164 - **Spread:** 656 - **Upper Limit:** 3409 - **Value:** 1042 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 71 - **Spread:** 434 - **Upper Limit:** 2308 - **Value:** 736 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 158 - **Spread:** 497 - **Upper Limit:** 2813 - **Value:** 680 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.31 - **Spread:** - **Upper Limit:** 4.54 - **Value:** 2.54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.13 - **Spread:** - **Upper Limit:** 5.15 - **Value:** 2.34 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 1.20 - **Spread:** - **Upper Limit:** 6.24 - **Value:** 2.63 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.06 - **Spread:** - **Upper Limit:** 3.89 - **Value:** 2.21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.26 - **Spread:** - **Upper Limit:** 5.59 - **Value:** 2.69 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 1.46 - **Spread:** - **Upper Limit:** 5.11 - **Value:** 2.93 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.53 - **Spread:** - **Upper Limit:** 0.44 - **Value:** -0.33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -0.81 - **Spread:** - **Upper Limit:** 1.76 - **Value:** 0.36 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** -2.97 - **Spread:** - **Upper Limit:** 1.99 - **Value:** 0.30 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics **Parameter Type:** NUMBER **Population Description:** All randomized patients **Reporting Status:** POSTED **Time Frame:** Up to end of treatment (data presented up to month 36) **Title:** Time to First Confirmed Morbidity or Mortality Event up to the End of Treatment (Kaplan-Meier Estimate of Patients Without a Morbidity or Mortality Event) **Type:** PRIMARY **Unit of Measure:** percentage of participants-Kaplan Meier ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 2 **Description:** Events of PAH or hospitalization for PAH up to the end of treatment included: death due to PAH, or onset of a treatment-emergent adverse event with a fatal outcome due to PAH occurring up to 4 weeks after the end of treatment, or hospitalisation for PAH up to the end of treatment. **Parameter Type:** NUMBER **Population Description:** All randomized patients **Reporting Status:** POSTED **Time Frame:** Up to end of treatment (data presented up to month 36) **Title:** Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event) **Type:** SECONDARY **Unit of Measure:** percentage of participants-Kaplan Meier ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 3 **Description:** Events of death due to any cause up to the end of treatment (plus 7 days) **Parameter Type:** NUMBER **Population Description:** All randomized patients **Reporting Status:** POSTED **Time Frame:** Up to end of treatment (data presented up to month 36) **Title:** Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event) **Type:** SECONDARY **Unit of Measure:** percentage of participants-Kaplan Meier ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 4 **Description:** Events of death due to any cause up to the end of study (EOS). The initiation of EOS procedure occurred when the target of 285 events was expected to have been achieved (30 January 2012). **Parameter Type:** NUMBER **Population Description:** All randomized patients **Reporting Status:** POSTED **Time Frame:** Up to end of study (data presented up to month 36) **Title:** Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event) **Type:** SECONDARY **Unit of Measure:** percentage of participants-Kaplan Meier ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 5 **Description:** The 6-minute walk test (6MWT) is a non-encouraged test, performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. These guidelines were provided to all sites. For patients who had never performed a 6MWT previously, a training test was required before the qualifying tests for inclusion were performed. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All randomized patients excluding 1 patient in the placebo group who did not start study treatment and 2 patients in the ACT-064992 3 mg group who did not follow appropriate consent procedures and were not included in the analysis **Reporting Status:** POSTED **Time Frame:** Baseline to month 6 **Title:** Change From Baseline to Month 6 in 6-minute Walk Distance **Type:** SECONDARY **Unit of Measure:** metres ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 6 **Description:** Class I: no limitation of usual physical activity (PA) which does not increase dyspnea, fatigue, chest pain, or presyncope. Class II: mild limitation of PA. No discomfort at rest. Normal PA increases dyspnea, fatigue, chest pain, or presyncope. Class III: marked limitation of PA. No discomfort at rest. Less than ordinary activity increases dyspnea, fatigue, chest pain, or presyncope. Class IV: unable to perform any PA and who may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. **Parameter Type:** NUMBER **Population Description:** All randomized patients excluding 1 patient in the placebo group who did not start study treatment and 2 patients in the ACT-064992 3 mg group who did not follow appropriate consent procedures and were not included in the analysis **Reporting Status:** POSTED **Time Frame:** Baseline to month 6 **Title:** Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6 **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 7 **Description:** In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period. **Dispersion Type:** Full Range **Parameter Type:** MEAN **Population Description:** All randomized patients participating in the pharmacokinetic/pharmacodynamic sub-study **Reporting Status:** POSTED **Time Frame:** Baseline to month 6 **Title:** Pulmonary Vascular Resistance at Baseline and Month 6 **Type:** SECONDARY **Unit of Measure:** (dyn*sec/cm^5) ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 8 **Description:** In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period. **Dispersion Type:** Full Range **Parameter Type:** MEAN **Population Description:** All randomized patients participating in the pharmacokinetic/pharmacodynamic sub-study **Reporting Status:** POSTED **Time Frame:** Baseline to month 6 **Title:** Cardiac Index at Baseline and Month 6 **Type:** SECONDARY **Unit of Measure:** L/min/m^2 ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg #### Outcome Measure 9 **Description:** Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics **Parameter Type:** NUMBER **Population Description:** All randomized patients **Reporting Status:** POSTED **Time Frame:** Up to end of treatment (Up to 36 months) **Title:** Summary of the First Causes of Morbidity or Mortality **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** participants ##### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** OG000 **Title:** Placebo ##### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** OG001 **Title:** ACT-064992 3 mg ##### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** OG002 **Title:** ACT-064992 10 mg ### Participant Flow Module #### Group **Description:** Matching ACT-064992 placebo tablet, once daily **ID:** FG000 **Title:** Placebo #### Group **Description:** ACT-064992 tablet, 3 mg, once daily **ID:** FG001 **Title:** ACT-064992 3 mg #### Group **Description:** ACT-064992 tablet, 10 mg, once daily **ID:** FG002 **Title:** ACT-064992 10 mg #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 44 ###### Reason **Group ID:** FG001 **Number of Subjects:** 47 ###### Reason **Group ID:** FG002 **Number of Subjects:** 34 ##### Withdraw **Type:** Withdrawal of consent ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ###### Reason **Group ID:** FG002 **Number of Subjects:** 4 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ##### Withdraw **Type:** Administrative reason ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Withdraw **Type:** Incorrect randomization ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 250 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 250 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 242 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 194 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 192 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 201 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 56 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 58 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 41 **Recruitment Details:** A total of 955 patients were screened from 158 centers in 39 countries, and 742 patients from 151 centers in 39 countries were randomized **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01744379 **Brief Title:** Single and Multiple Dose Study in Japanese **Official Title:** A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of Lesinurad in Healthy Male Japanese Subjects #### Organization Study ID Info **ID:** RDEA594-125 #### Organization **Class:** INDUSTRY **Full Name:** Ardea Biosciences, Inc. ### Status Module #### Completion Date **Date:** 2013-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-06-19 **Type:** ESTIMATED **Last Update Submit Date:** 2013-06-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-03 **Type:** ACTUAL #### Start Date **Date:** 2012-12 **Status Verified Date:** 2013-06 #### Study First Post Date **Date:** 2012-12-06 **Type:** ESTIMATED **Study First Submit Date:** 2012-11-29 **Study First Submit QC Date:** 2012-12-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Ardea Biosciences, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will explore the safety, tolerability, and serum uric acid lowering effect of lesinurad in healthy Japanese males to allow comparison with the Western population. **Detailed Description:** While there is extensive clinical experience with lesinurad in the Western population, it is recognized that both intrinsic and extrinsic factors may impact the PK, PD, safety, and dose response in different ethnic populations. The purpose of this study is to explore the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of single and multiple doses of lesinurad in healthy Japanese males, and to allow comparison of these parameters with the Western population. ### Conditions Module **Conditions:** - Gout ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 200 mg lesinurad or placebo fasted and fed **Intervention Names:** - Drug: Lesinurad - Drug: Placebo **Label:** 200 mg lesinurad **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 400 mg lesinurad or placebo fasted and fed **Intervention Names:** - Drug: Lesinurad - Drug: Placebo **Label:** 400 mg lesinurad **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 100 mg lesinurad or placebo fasted and fed **Intervention Names:** - Drug: Lesinurad - Drug: Placebo **Label:** 100 mg lesinurad **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** 50 mg lesinurad or placebo fasted and fed **Intervention Names:** - Drug: Lesinurad - Drug: Placebo **Label:** 50 mg lesinurad **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** 600 mg lesinurad or placebo fasted and fed **Intervention Names:** - Drug: Lesinurad - Drug: Placebo **Label:** 600 mg lesinurad **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 100 mg lesinurad - 200 mg lesinurad - 400 mg lesinurad - 50 mg lesinurad - 600 mg lesinurad **Name:** Lesinurad **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 100 mg lesinurad - 200 mg lesinurad - 400 mg lesinurad - 50 mg lesinurad - 600 mg lesinurad **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Incidence of Adverse Events and Changes in Laboratory Parameters **Time Frame:** 5 to 6 weeks **Description:** AUC: area under the plasma concentration time curve from zero to 24 hours post dose and from zero to infinity; tmax: time to maximum plasma concentration; cmax: maximum observed plasma concentration t1/2: terminal elimination half life **Measure:** Pharmacokinetic (PK) profile of lesinurad from plasma and urine in terms of AUC, tmax, cmax and t1/2. **Time Frame:** Day -1 through 12 **Measure:** Pharmacodynamic (PD) profile of lesinurad from serum and urine in terms of sUA concentration, renal clearance, urine uric acid excretion, and fractional excretion. **Time Frame:** Day 1 through 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Able to understand the study procedures, the risks involved and willing to provide written Informed Consent before the first study related activity. * Healthy adult subjects born in Japan * All laboratory parameters should be within normal limits or considered not clinically significant by the investigator. * Screening serum uric acid level \>= 4.5 mg/dL. * Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with study evaluations or procedures. * Subject does not have clinically relevant abnormalities in blood pressure, heart rate, body temperature, and respiratory rate, as per the Investigator's judgment. Exclusion Criteria: * Positive serology to Human Immunodeficiency Virus (HIV-1 and HIV-2). * Positive test for active Hepatitis B or Hepatitis C infection. * History of kidney stones. * Undergone major surgery within 3 months of Day 1. * Subject has received the last dose of an investigational drug (or treatment with a medical device) within 30 days or 5 half-lives (whichever is longer) of the investigational drug prior to Day 1 or are currently participating in another study of an investigational drug (or medical device). * Prior exposure to lesinurad (RDEA594) or RDEA806. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 20 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Glendale **Country:** United States **State:** California **Zip:** 91206 #### Overall Officials **Official 1:** **Affiliation:** Ardea Biosciences, Inc. **Name:** S Bradley, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9177 - Name: Gout - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000006074 - Term: Gout Suppressants - ID: D000018501 - Term: Antirheumatic Agents - ID: D000014528 - Term: Uricosuric Agents ### Intervention Browse Module - Browse Branches - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M262584 - Name: Lesinurad - Relevance: HIGH - As Found: Recurrent small lymphocytic lymphoma - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000593471 - Term: Lesinurad ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05325879 **Brief Title:** Relationship of Cervical Region Tension With Vagal Function **Official Title:** Investigation of the Relationship of Cervical Region Tension With Vagal Function and Gastrointestinal Symptoms #### Organization Study ID Info **ID:** HUSpine014 #### Organization **Class:** OTHER **Full Name:** Hacettepe University ### Status Module #### Completion Date **Date:** 2023-09-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-09-15 **Type:** ACTUAL #### Start Date **Date:** 2022-08-15 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2022-04-13 **Type:** ACTUAL **Study First Submit Date:** 2022-04-06 **Study First Submit QC Date:** 2022-04-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hacettepe University #### Responsible Party **Investigator Affiliation:** Hacettepe University **Investigator Full Name:** Yasemin Özel Aslıyüce **Investigator Title:** Research Assistant **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The increase in the tension of the soft tissues around a nerve restricts the movement, affects the function of the nerve, and makes the nerve vulnerable to entrapment. Even a mild nerve compression can cause entrapment and lead to neuroinflammation. It is known that inflammatory mediators amplify axonal sensitivity. Although the spontaneous discharge potential of visceral afferents is quite low under normal conditions, neuroinflammation increases the excitability of these fibers. With this mechanism, hyperalgesia may develop in sensory fibers in neuroinflammation. This may cause pathologies in the organs innervated by the relevant nerve. The fascia and muscles of the cervical region surround the vagus nerve. There are two main fascial compartments in the cervical region. The SCM and trapezius muscle fascias join to the most superficial fascia of the deep cervical fascia and they together form these compartments. These fasciae superiorly attach to the cranium and inferiorly to the pectoral region. The vagus nerve emerges from the jugular foramen together with the 9th and 11th cranial nerves. It then continues through the carotid sheath in the cervical region. The carotid sheath is in contact with the SCM muscle. For this reason, it can be thought that SCM muscle tension or thickness may affect the carotid sheath and thus the function of the vagus nerve passing through it. In summary, deterioration in vagus nerve activity plays a role in pathologies of the organs innervated by the vagus. Although the relationship between vagal dysfunction and gastrointestinal system symptoms is clear, the mechanisms affecting vagus nerve function have not yet been clarified. It has been reported in the literature that some maneuvers from the cervical region are also effective on the vagus nerve. Also, according to investigators' clinical experience, gastrointestinal symptoms are frequently observed in patients with increased cervical soft tissue tension. However, there are not enough studies investigating whether the cervical region soft tissue tension can affect the gastrointestinal system via the vagus nerve. Therefore, this study was planned to examine the relationship of cervical soft tissue tension with vagus nerve function and gastrointestinal symptoms in asymptomatic individuals and individuals with neck pain. ### Conditions Module **Conditions:** - Gastrointestinal Diseases - Autonomic Nervous System Disease **Keywords:** - vagus nerve - muscle tonus - Autonomic Nervous System Diseases - Pain Threshold ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** SCREENING #### Enrollment Info **Count:** 41 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individuals aged between 18-50 who volunteered to participate in the study, will form the control group. **Intervention Names:** - Other: VAGUS-NDT **Label:** Asymptomatic Individuals **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Individuals with neck pain aged between 18-50 who volunteered to participate in the study, will form the study group. **Intervention Names:** - Other: VAGUS-NDT **Label:** Individuals with neck pain **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Asymptomatic Individuals - Individuals with neck pain **Description:** Neurodynamic test for vagus nerve **Name:** VAGUS-NDT **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Vagus nerve function will be evaluated with the Vagus Neurodynamic Test (VAGUS-NDT). Carta et al. VAGUS-NDT, which was validated and reliable in 2020, evaluates vagal function selectively. The test is performed with the patient in the supine position. The test is considered positive if unpleasant sensations are described when pressure is applied to the abdomen after the head is placed in cervicocranial flexion, lateral flexion, and rotation. **Measure:** Evaluation of Vagal Function **Time Frame:** 10 minutes, in one assessment session **Description:** SCM muscle tension will be performed with Myoton-3 (Muomeetria AS, Tallinn, Estonia) myometer. Myometer is a high validity and reliability method used to evaluate muscle tension. During the measurement, the device will give the tension of the muscle numerically by making a light touch on the skin. For the measurement, the myotone will be placed perpendicular to the midpoint between the anterior surface of the manubrium sterni and the mastoid process of the temporal bone, and an average of 10 measurements will be used. **Measure:** Evaluation of SCM Muscle Tension **Time Frame:** 10 minutes, in one assessment session. **Description:** Hospital Anxiety and Depression Scale was developed by Zigmond and Snaith, and the Turkish version of the scale was published by Aydemir et al. The scale consists of 14 items, 7 of which assess anxiety and 7 of which assess depression symptoms. It is a 4-point Likert scale type and is scored between 0-3. A high score indicates high levels of anxiety and depression **Measure:** Hospital Anxiety and Depression Scale **Time Frame:** 10 minutes, in one assessment session #### Secondary Outcomes **Description:** The level of neck disability will be evaluated using the The Neck Disability Questionnaire. It was developed by Vernon et al. as a neck version of the Oswestry Low Back Pain Scale. Within the scope of this study, the Neck Disability Questionnaire will be applied to the participants with a neck pain severity of 3 and above on the Numerical Pain Rating Scale. The Neck Disability Questionnaire includes ten questions about pain, personal care, concentration, work, driving, and sleeping. Each question is scored between 0-5 points. The total score is evaluated out of 50. A high score means a high disability. **Measure:** Evaluation of Neck Disability **Time Frame:** 5 minutes, in one assessment session. **Description:** Pain intensity will be assessed using the Numerical Pain Rating Scale. The 11-item version of the scale, which is frequently used to measure the severity of pain in adults, will be used. Within the scope of this study, a scale will be used to measure the severity of neck pain of the participants. With this scale, participants will be asked to measure their neck pain on a scale of 0-10. A value of '0' indicates no pain and a value of '10' indicates excruciating pain. **Measure:** Evaluation of Pain Intensity **Time Frame:** 1 minutes, in one assessment session. **Description:** Gastrointestinal symptoms will be evaluated using the Gastrointestinal Symptoms Rating Scale. Revicki et al. The scale developed by CBS measures common symptoms in CBS diseases. A seven-point Likert-type scale consisting of 15 items consisting of five sub-dimensions was made in order. These sub-dimensions are; reflux, indigestion, diarrhea, constipation and abdominal pain. The total score ranges from 15 to 105, with a high score indicating severe symptoms. **Measure:** Evaluation of Gastrointestinal Symptoms **Time Frame:** 5 minutes, in one assessment session. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Being 18-50 of age, * Having less than 30 body mass index, * Being a volunteer Exclusion Criteria: * Having any type of malign disease, * Being diagnosed with a systemic disease (cardiologic, gastrointestinal, rheumatological, neurological, etc.), * Having any type of surgery within the last 6 months, * Being diagnosed with Whiplash syndrome * Having an unhealed fracture * Pregnancy * Using prescribed medicine for the gastrointestinal system **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ankara **Country:** Turkey **Facility:** Yasemin Özel Aslıyüce **State:** Sıhhiye **Zip:** 06100 #### Overall Officials **Official 1:** **Affiliation:** Hacettepe University **Name:** Utku Berberoğlu, MSc **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Hacettepe University **Name:** Özgün Uysal, MSc **Role:** STUDY_CHAIR **Official 3:** **Affiliation:** Hacettepe University **Name:** Özlem Ülger, Professor **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: HIGH - As Found: Gastrointestinal Diseases - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: HIGH - As Found: Gastrointestinal Diseases - ID: M4643 - Name: Autonomic Nervous System Diseases - Relevance: HIGH - As Found: Autonomic Nervous System Diseases - ID: M27979 - Name: Primary Dysautonomias - Relevance: HIGH - As Found: Autonomic Nervous System Diseases ### Condition Browse Module - Meshes - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000001342 - Term: Autonomic Nervous System Diseases - ID: D000054969 - Term: Primary Dysautonomias ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01351779 **Brief Title:** The Effect of Body Posture on Intraocular Pressure in Progressive Glaucoma **Official Title:** The Effect of Body Posture on Intraocular Pressure in Progressive Glaucoma #### Organization Study ID Info **ID:** 10-0844-A #### Organization **Class:** OTHER **Full Name:** University of Toronto ### Status Module #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2011-05-11 **Type:** ESTIMATED **Last Update Submit Date:** 2011-05-09 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2012-05 **Type:** ESTIMATED #### Start Date **Date:** 2011-05 **Status Verified Date:** 2011-05 #### Study First Post Date **Date:** 2011-05-11 **Type:** ESTIMATED **Study First Submit Date:** 2011-05-09 **Study First Submit QC Date:** 2011-05-09 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Sensimed AG #### Lead Sponsor **Class:** OTHER **Name:** University of Toronto #### Responsible Party **Old Name Title:** Professor Graham Trope **Old Organization:** University of Toronto ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Glaucoma is a condition where the optic nerve (the nerve responsible for sight) shows progressive damage with characteristic loss of visual field. Glaucoma is very commonly associated with raised pressure in the eye (intraocular pressure \[IOP\]). IOP has been shown to increase when lying down in normal subjects as well as patients with glaucoma. It is possible that this effect can make glaucoma worse. This study is designed to investigate the effect of body posture (particularly when sleeping) on the IOP fluctuation in the eye. Each patient will be required to attend for 2 separate 24 hour visits. On one visit the patient will be required to sleep flat and on the other visit at a 30° head up sleeping position. During this time the patient will be required to wear a soft contact lens (SENSIMED Triggerfish®) which has a special sensor on it that monitors the IOP continuously. The IOP measurements are wirelessly transmitted to a recorder. ### Conditions Module **Conditions:** - Glaucoma **Keywords:** - Intraocular pressure - Contact lens sensor - Optic disc hemorrhage ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with primary open angle glaucoma identified to have an optic disc hemorrhage **Label:** Progressive glaucoma ### Outcomes Module #### Primary Outcomes **Description:** The intraocular pressure will be continuously monitored with a wireless contact lens sensor device over a 24 hour period **Measure:** Intraocular pressure changes that occur during sleep and with changes in body posture **Time Frame:** 24 hours #### Secondary Outcomes **Description:** Patients will be monitored for contact lens related side effects or adverse effects that occur during the monitoring session. **Measure:** Incidence of side effects or adverse effects that occur while subjects are wearing the contact lens device **Time Frame:** 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * signed informed consent * diagnosis of primary open angle glaucoma (POAG) or normal tension glaucoma (NTG) that is progressing based on recent or recurrent optic disc hemorrhage * age 18-85 years * not more than 4 diopters of spherical equivalent or 2 diopters of cylinder equivalent in study eye * stable anti-glaucoma treatment for 4 weeks before first session * for women of childbearing potential, adequate contraception Exclusion Criteria: * unwilling or unable to sleep in a flat or 30 degrees head up position * ocular surgery in previous 3 months * corneal or conjunctival abnormality * wear of full frame metallic glasses during monitoring session * severe dry eye * secondary forms of glaucoma * allergy to corneal anaesthesia * patients with contraindications for contact lens wear * pregnancy and lactation * patients unable to understand the character and individual consequences of the investigation * simultaneous participation in other research **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Glaucoma clinic patients ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** Graham.Trope@uhn.on.ca **Name:** Graham Prof Trope, PhD, FRCSC **Phone:** 4166035317 **Role:** CONTACT **Contact 2:** **Email:** y.buys@utoronta.ca **Name:** Yvonne Prof Buys, MD, FRCSC **Phone:** 4166035682 **Role:** CONTACT #### Locations **Location 1:** **City:** Toronto **Contacts:** ***Contact 1:*** - **Email:** raham.Trope@uhn.on.ca - **Name:** Graham Prof Trope, PhD, FRCSC - **Phone:** 4166035317 - **Role:** CONTACT ***Contact 2:*** - **Name:** Graham E Trope, PhD, FRCSC - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Yvonne M Buys, MD, FRCSC - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Hussain Patel, MD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** John Flanagan, DO, PhD - **Role:** SUB_INVESTIGATOR ***Contact 6:*** - **Name:** Colin Shapiro, MD, PhD - **Role:** SUB_INVESTIGATOR ***Contact 7:*** - **Name:** Farzana Jahan, MD - **Role:** SUB_INVESTIGATOR **Country:** Canada **Facility:** Toronto Western Hospital **State:** Ontario **Status:** RECRUITING **Zip:** M5T 2S8 ### References Module #### References **Citation:** Beltran-Agullo L, Buys YM, Jahan F, Shapiro CM, Flanagan JG, Cheng J, Trope GE. Twenty-four hour intraocular pressure monitoring with the SENSIMED Triggerfish contact lens: effect of body posture during sleep. Br J Ophthalmol. 2017 Oct;101(10):1323-1328. doi: 10.1136/bjophthalmol-2016-308710. Epub 2017 Mar 7. **PMID:** 28270491 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009798 - Term: Ocular Hypertension - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: LOW - As Found: Unknown - ID: M9013 - Name: Glaucoma - Relevance: HIGH - As Found: Glaucoma - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M12731 - Name: Ocular Hypertension - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005901 - Term: Glaucoma ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03312179 **Brief Title:** STEMI and Incretins Treatment **Official Title:** STEMI and Mutlivessels Coronary Artery Stenosis: Effect of Incretin Treatment #### Organization Study ID Info **ID:** 9/2017 #### Organization **Class:** OTHER **Full Name:** University of Campania "Luigi Vanvitelli" ### Status Module #### Completion Date **Date:** 2017-10-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-10-19 **Type:** ACTUAL **Last Update Submit Date:** 2017-10-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-09-01 **Type:** ACTUAL #### Start Date **Date:** 2017-01-01 **Type:** ACTUAL **Status Verified Date:** 2017-10 #### Study First Post Date **Date:** 2017-10-17 **Type:** ACTUAL **Study First Submit Date:** 2017-10-12 **Study First Submit QC Date:** 2017-10-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Campania "Luigi Vanvitelli" #### Responsible Party **Investigator Affiliation:** University of Campania "Luigi Vanvitelli" **Investigator Full Name:** Celestino Sardu **Investigator Title:** MD, MSc, PHD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** ST elevation myocardial infarction (STEMI) patients affected by multivessels coronary artery stenosis, represent a clinical relevant problem. The management and prognosis of these patents are supported by few literature data. Therefore, in this study authors enrolled real world diabetic vs. non diabetic patients admitted for STEMI and associated to multi vessels coronary disease. Then these diabetics were divided in incretin users (6 months of incretin treatment before study enrollment) vs. never incretin users. In these patients authors studied all cause mortality, cardiac mortality, and major adverse cardiac events at 12 months follow up. **Detailed Description:** ST elevation myocardial infarction (STEMI) patients affected by multivessels coronary artery stenosis represent a class of patients really challenging to treat. In fact, treatment, clinical management, and prognosis are supported by few literature data. Therefore, in this study authors enrolled real world patients admitted for STEMI and associated to multi vessels coronary disease. Multivessels (Mv) coronary stenosis were characterized by non obstructive coronary stenosis (NOCS) as coronary lesions \<50% with fractional flow reserve \> 0.8. Therefore, STEMI was treated by percutaneous coronary intervention by primary angioplasty and direct stenting (DES stenting) of culprit vessel lesion. Then these STEMI-Mv-NOCS patients were divided in diabetics vs. non diabetics, and received conventional full medical therapy for STEMI. Then these diabetics were divided in incretin users (6 months of incretin treatment before study enrollment) vs. never incretin users. Study outcomes were all cause mortality, cardiac mortality, and major adverse cardiac events at 12 months follow up. Authors studied these study outcomes comparing diabetics vs. non diabetics at 12 moths follow up, and diabetics incretin-users vs. never-incretin-users. ### Conditions Module **Conditions:** - STEMI - Coronary Artery Disease - Coronary Syndrome - Coronary Arteriosclerosis - Diabetes ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 900 **Type:** ACTUAL **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 12 Months ### Arms Interventions Module #### Arm Group 1 **Description:** Diabetics patients admitted for ST elevation myocardial infarction (STEMI) and associated with multi vessels (Mv) non obstructive coronary artery stenosis (NOCS). These patients received percutaneous coronary intervention (PCI), and primary stenting (DES) of culprit lesion. Then these patients received full medical STEMI therapy. **Intervention Names:** - Device: PCI and DES stenting **Label:** diabetics STEMI #### Arm Group 2 **Description:** Non diabetics patients admitted for ST elevation myocardial infarction (STEMI) and associated with multi vessels coronary artery stenosis(Mv) non obstructive coronary artery stenosis (NOCS). These patients received percutaneous coronary intervention (PCI), and primary stenting (DES) of culprit lesion. Then these patients received full medical STEMI therapy. **Intervention Names:** - Device: PCI and DES stenting **Label:** non diabetics STEMI #### Arm Group 3 **Description:** Diabetics patients admitted for ST elevation myocardial infarction (STEMI) and associated with multi vessels coronary artery stenosis (Mv) non obstructive coronary artery stenosis (NOCS). These patients received percutaneous coronary intervention (PCI), and primary stenting (DES) of culprit lesion. Then these patients received full medical STEMI therapy. These patients were treated by incretin therapy at last 6 months before study enrollment. **Intervention Names:** - Device: PCI and DES stenting - Drug: Incretins **Label:** diabetics incretin-users STEMI #### Arm Group 4 **Description:** Diabetics patients admitted for ST elevation myocardial infarction (STEMI) and associated with multi vessels coronary artery stenosis (Mv) non obstructive coronary artery stenosis (NOCS). These patients received percutaneous coronary intervention (PCI), and primary stenting (DES) of culprit lesion. Then these patients received full medical STEMI therapy. These diabetic patients were never treated by incretin therapy before study enrollment. **Intervention Names:** - Device: PCI and DES stenting **Label:** diabetics never-incretin-users STEMI ### Interventions #### Intervention 1 **Arm Group Labels:** - diabetics STEMI - diabetics incretin-users STEMI - diabetics never-incretin-users STEMI - non diabetics STEMI **Description:** Percutaneous coronary intervention (PCI) and direct stenting (DES) of culprit lesion vessel. **Name:** PCI and DES stenting **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - diabetics incretin-users STEMI **Description:** Patients treated before study enrollment by incretin drugs (6 months drugs exposure) **Name:** Incretins **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** at 12 months follow up authors monitored and reported all cause mortality **Measure:** all cause deaths **Time Frame:** 12 months **Description:** at 12 months follow up authors monitored and reported mortality events due to cardiac causes **Measure:** cardiac deaths **Time Frame:** 12 months **Description:** authors monitored and reported at follow up major adverse cardiac events (MACE): re-STEMI, NSTEMI, unstable angina, arrhythmias, stroke etc. **Measure:** MACE **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: aged \>18, first STEMI, STEMI with multi vessels coronary stenosis. Exclusion Criteria: aged \< 18, renal impairment, mono vessel STEMI, severe depression of left ventricle ejection fraction (LVEF \<35%). **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Diabetics and non diabetics patients admitted for STEMI. In this population authors selected STEMI patients with multivessel (Mv) non obstructive coronary diseases (NOCS). These STEMI-Mv-NOCS had coronary lesions and stenosis \<50%, with fractional flow reserve \>0.8. In diabetics authors selected incretin users (6 months of incretin treatment before study enrollment) vs never-incretin-users diabetics. ### Contacts Locations Module #### Locations **Location 1:** **City:** Naples **Country:** Italy **Facility:** Raffaele Marfella **Zip:** 80128 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003327 - Term: Coronary Disease - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000009203 - Term: Myocardial Infarction - ID: D000007238 - Term: Infarction - ID: D000007511 - Term: Ischemia - ID: D000010335 - Term: Pathologic Processes - ID: D000009336 - Term: Necrosis ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M1072 - Name: ST Elevation Myocardial Infarction - Relevance: HIGH - As Found: STEMI - ID: M6549 - Name: Coronary Disease - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Arteriosclerosis - ID: M19506 - Name: Myocardial Ischemia - Relevance: HIGH - As Found: Coronary Arteriosclerosis - ID: M6475 - Name: Constriction, Pathologic - Relevance: LOW - As Found: Unknown - ID: M22913 - Name: Coronary Stenosis - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: HIGH - As Found: Arteriosclerosis - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M12155 - Name: Myocardial Infarction - Relevance: LOW - As Found: Unknown - ID: M10282 - Name: Infarction - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003324 - Term: Coronary Artery Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000072657 - Term: ST Elevation Myocardial Infarction - ID: D000001161 - Term: Arteriosclerosis ### Intervention Browse Module - Ancestors - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M27905 - Name: Incretins - Relevance: HIGH - As Found: TPC - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000054795 - Term: Incretins ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00322179 **Brief Title:** Microarray Analysis of IFN-Induced Gene Expression in Obese and Non-Obese Patients With Chronic Hepatitis C **Official Title:** Microarray Analysis of IFN-Induced Gene Expression in Obese and Non-Obese Patients With Chronic Hepatitis C #### Organization Study ID Info **ID:** CHR0036ARG #### Organization **Class:** OTHER **Full Name:** Palo Alto Veterans Institute for Research #### Secondary ID Infos **ID:** PEG215 ### Status Module #### Completion Date **Date:** 2008-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-04 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-11 **Type:** ACTUAL #### Start Date **Date:** 2005-11 **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2006-05-05 **Type:** ESTIMATED **Study First Submit Date:** 2006-05-04 **Study First Submit QC Date:** 2006-05-04 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Lead Sponsor **Class:** OTHER **Name:** Palo Alto Veterans Institute for Research #### Responsible Party **Investigator Affiliation:** Palo Alto Veterans Institute for Research **Investigator Full Name:** Ramsey Cheung **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** The response rate to interferon-based anti-viral therapy for chronic hepatitis C is lower in patients who are obese. However, it is not clear whether this is related to suboptimal dosing of the medication or alterated response in obese patients. Alterated immune response had been reported in obese patients. The goal of current study is to determine the immune response to interferon in obese compared to non-obese chronic hepatitis C in an tissue culture system. **Detailed Description:** To examine our hypothesis, we will incubate PBMC samples from obese and nonobese patients with IFN, followed by microarray analysis to compare the IFN response patterns in both groups of patients and to identify genes differentially regulated between these two groups. Identification of such genes will provide important insight to the mechanism of the antiviral effect of HCV. The identified genes will have the potential of serving as targets for pharmaceutical intervention aiming at enhancing the efficacy of IFN therapy for obese patients. This is an open-label study. Ten obese and 10 nonobese patients with chronic hepatitis C will be recruited. For the purpose of this study, obese is defined as body weight \>85 kg and BMI \>30, and nonobese as body weight \<75 kg and BMI\<25. ### Conditions Module **Conditions:** - Chronic Hepatitis C - Obesity **Keywords:** - Microarray Analysis - Obesity - Chronic Hepatitis C ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** OTHER #### Enrollment Info **Count:** 22 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Obese #### Arm Group 2 **Label:** Non-Obese ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * obese (weight \> 85kg and BMI\>30) or non-obese patients (\<75kg and BMI \<25) with chronic Hepatitis C * Chronic Hepatitis C infection with documented HCV RNA * Body habitat either as obese or non-obese as defined above * Currently not under IFN therapy * Non-African American Exclusion Criteria: * Body habitat neither obese or non-obese as defined for the purpose of this study * Unable to give consent * On immunomodulatory agents such as prednisone * Active infection other than Hepatitis C * Co-infection with HBV or HIV * Active or excessive alcohol use * Other cause of chronic Hepatitis **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Inclusion Criteria: * obese (weight \> 85kg and BMI\>30) or non-obese patients (\<75kg and BMI \<25) with chronic Hepatitis C * Chronic Hepatitis C infection with documented HCV RNA * Body habitat either as obese or non-obese as defined above * Currently not under IFN therapy * Non-African American ### Contacts Locations Module #### Locations **Location 1:** **City:** Palo Alto **Country:** United States **Facility:** VA Palo Alto Health Care System **State:** California **Zip:** 94304 #### Overall Officials **Official 1:** **Affiliation:** VA Palo Alto Health Care System **Name:** Ramsey Cheung, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Bressler BL, Guindi M, Tomlinson G, Heathcote J. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology. 2003 Sep;38(3):639-44. doi: 10.1053/jhep.2003.50350. **PMID:** 12939590 **Citation:** Camps J, Crisostomo S, Garcia-Granero M, Riezu-Boj JI, Civeira MP, Prieto J. Prediction of the response of chronic hepatitis C to interferon alfa: a statistical analysis of pretreatment variables. Gut. 1993 Dec;34(12):1714-7. doi: 10.1136/gut.34.12.1714. **PMID:** 7904252 **Citation:** Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002 Oct;110(8):1093-103. doi: 10.1172/JCI15693. **PMID:** 12393845 **Citation:** Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047. **PMID:** 12324553 **Citation:** Ji X, Cheung R, Cooper S, Li Q, Greenberg HB, He XS. Interferon alfa regulated gene expression in patients initiating interferon treatment for chronic hepatitis C. Hepatology. 2003 Mar;37(3):610-21. doi: 10.1053/jhep.2003.50105. Erratum In: Hepatology. 2003 Jun;37(6):1503. **PMID:** 12601359 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections - ID: D000004769 - Term: Enterovirus Infections - ID: D000010850 - Term: Picornaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000018178 - Term: Flaviviridae Infections - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9607 - Name: Hepatitis, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M21613 - Name: Hepatitis C, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis C - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M7930 - Name: Enterovirus Infections - Relevance: LOW - As Found: Unknown - ID: M13745 - Name: Picornaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000019698 - Term: Hepatitis C, Chronic - ID: D000006505 - Term: Hepatitis - ID: D000006521 - Term: Hepatitis, Chronic ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05043779 **Brief Title:** Evaluation of Preoperative Nasoendoscopy to Predict Difficult Intubation **Official Title:** Is Preoperative Awake Airway Nasoendoscopy A Good Tool To Predict The Expected Difficult Airway In Obese Patients? #### Organization Study ID Info **ID:** MRC-01-19-107 #### Organization **Class:** INDUSTRY **Full Name:** Hamad Medical Corporation ### Status Module #### Completion Date **Date:** 2022-03-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-09-14 **Type:** ACTUAL **Last Update Submit Date:** 2021-09-05 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-03-01 **Type:** ESTIMATED #### Start Date **Date:** 2020-08-12 **Type:** ACTUAL **Status Verified Date:** 2021-07 #### Study First Post Date **Date:** 2021-09-14 **Type:** ACTUAL **Study First Submit Date:** 2021-07-28 **Study First Submit QC Date:** 2021-09-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hamad Medical Corporation #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Despite the availability of different methods for airway assessment, unexpectedly difficult intubations occur at a frequency of up to 15%. A variety of pre-intubation clinical screening tests have been advocated to predict difficult laryngoscopy and airway but their usefulness is limited in obese patients. Could awake invasive airway assessment be more predictive for difficult airways in obese patients? The use of nasendoscopy assessment for the airway could be a useful additional invasive tool to predict the difficult airway in obese **Detailed Description:** Predictors of difficult laryngoscopy and intubation may be less useful or irrelevant when there is a plan for video laryngoscopes (VL) intraoperative. VL improves laryngeal view in most patients, Their use achieves a high success rate for intubation of patients with predicted difficult intubation, and those who have failed direct laryngoscopy\[6\]. In a study of over 2000 (VL) video laryngoscopies intubations, Mallampati's score did not correlate with failed intubation. The strongest predictor of failure was neck pathology, including the presence of a surgical scar, radiation changes, or mass. In another study, risk factors for difficult VL intubation after direct laryngoscopy were Cormack-Lehane grade 3 or 4 views with direct laryngoscopy, short sternothyroid distance, and high upper lip bite test score. Obesity is a recognized risk factor for difficulty with airway management. An audit of major complications of airway management (NAP4) from over three million anesthetics in the United Kingdom found twice as many case reports of major complications in obese patients, especially in the morbidly obese. It is less clear whether obesity increases the risk of difficult laryngoscopy or intubation. Some studies suggest that obesity is a risk factor for both difficult mask ventilation and difficult laryngoscopy, while other studies suggest that with proper positioning and preparation, ventilation and laryngoscopy are not difficult \[12,13\]. Wilson's score is an important development in predictivity of airway difficulties, Wilson's in his study (1988) attempted to deductively identify patients for whom intubation will be difficult. This study aims to demonstrate the use of preoperative awake fibreoptic examination ### Conditions Module **Conditions:** - Difficult or Failed Intubation - Obesity, Morbid **Keywords:** - Nasoendoscopy, - Obesity, - Difficult intubation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** only one arm **Intervention Names:** - Procedure: Awake Airway Nasoendoscopy **Label:** Preoperative Awake Airway Nasoendoscopy **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Preoperative Awake Airway Nasoendoscopy **Description:** Preoperative Awake Airway Nasoendoscopy of upper airway **Name:** Awake Airway Nasoendoscopy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Findings will be recorded and scored according to NOHL (N=nose, O= oral, H= hypopharynx and L= Larynx ) every parameter takes a score from 1- 4 during pre-operative assessment.(the maximum values score = 16 and the minimum = 4) **Measure:** Naso-endoscopy views from nose to larynx in obese patients using NOHL score during pre-operative assessment. **Time Frame:** During pre-operative assessment. #### Secondary Outcomes **Description:** This will be measured by centimeter during pre-operative assessment using a ruler **Measure:** Measurement of neck circumference in Centimeter **Time Frame:** During pre-operative assessment. **Description:** This will be measured by centimeter between incisors during pre-operative assessment using a ruler and documented by Centimeter **Measure:** Mouth opening measurement by Centimeter **Time Frame:** During pre-operative assessment. **Description:** This will be measured by centimeter from thyroid cartilage to patient's chin during pre-operative assessment using a rule **Measure:** Thyro-mental distance measurement by Centimeter **Time Frame:** During pre-operative assessment. **Description:** Degree of Difficulty in mask ventilation will be graded (1= easy, 2= difficult or 3=impossible) during induction of general anaesthesia **Measure:** Difficult mask ventilation score (1 -3) **Time Frame:** During Induction of anesthesia **Description:** Cormak-Lehans Score will graded during endotracheal intubation and exposure of the larynx. (Grade 1= easy intubation while grade Grade 4= very difficult intubation) **Measure:** Cormak-Lehans grade during induction of anaesthesia **Time Frame:** During intubation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients between 18-60 years of age either male or female with (ASA I, II or III ), scheduled for a bariatric procedure with a body mass index (BMI) greater than 35 K/M2, will be enrolled Exclusion Criteria: * Patients on the tracheostomy tube * Patients who are unable to give consent **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** nshallik@hamad.qa **Name:** nabil Shallik, M.D. **Phone:** 9745543926 **Role:** CONTACT #### Locations **Location 1:** **City:** Doha **Contacts:** ***Contact 1:*** - **Email:** nshallik@outlook.com - **Name:** Nabil Shallik, M.D. - **Phone:** 55439284 - **Role:** CONTACT ***Contact 2:*** - **Name:** Mohamed A. Elarref, M.D. - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Mayed Radi, M.D. - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Olfa Al Mannai, M.D. - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 5:*** - **Name:** Adnan Saad Eddin, MBBcH - **Role:** SUB_INVESTIGATOR ***Contact 6:*** - **Name:** Yasser Hammad, M.D. - **Role:** SUB_INVESTIGATOR **Country:** Qatar **Facility:** ACC, Hamad Medical Corporation **State:** Doah **Status:** RECRUITING **Zip:** 3050 #### Overall Officials **Official 1:** **Affiliation:** Hamad Medical Corporation - HMC **Name:** Nabil Shallik, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Through Website **Description:** We will share after IRB approval **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** After approval IRB directly ### References Module #### References **Citation:** Butler PJ, Dhara SS. Prediction of difficult laryngoscopy: an assessment of the thyromental distance and Mallampati predictive tests. Anaesth Intensive Care. 1992 May;20(2):139-42. doi: 10.1177/0310057X9202000202. **PMID:** 1595845 **Citation:** Janssens M, Hartstein G. Management of difficult intubation. Eur J Anaesthesiol. 2001 Jan;18(1):3-12. doi: 10.1046/j.0265-0215.2000.00777.x. **PMID:** 11270007 **Citation:** Qudaisat IY, Al-Ghanem SM. Short thyromental distance is a surrogate for inadequate head extension, rather than small submandibular space, when indicating possible difficult direct laryngoscopy. Eur J Anaesthesiol. 2011 Aug;28(8):600-6. doi: 10.1097/EJA.0b013e328347cdd9. **PMID:** 21610502 **Citation:** Langeron O, Masso E, Huraux C, Guggiari M, Bianchi A, Coriat P, Riou B. Prediction of difficult mask ventilation. Anesthesiology. 2000 May;92(5):1229-36. doi: 10.1097/00000542-200005000-00009. **PMID:** 10781266 **Citation:** Tremblay MH, Williams S, Robitaille A, Drolet P. Poor visualization during direct laryngoscopy and high upper lip bite test score are predictors of difficult intubation with the GlideScope videolaryngoscope. Anesth Analg. 2008 May;106(5):1495-500, table of contents. doi: 10.1213/ane.0b013e318168b38f. **PMID:** 18420866 **Citation:** Samsoon GL, Young JR. Difficult tracheal intubation: a retrospective study. Anaesthesia. 1987 May;42(5):487-90. doi: 10.1111/j.1365-2044.1987.tb04039.x. **PMID:** 3592174 **Citation:** Sun DA, Warriner CB, Parsons DG, Klein R, Umedaly HS, Moult M. The GlideScope Video Laryngoscope: randomized clinical trial in 200 patients. Br J Anaesth. 2005 Mar;94(3):381-4. doi: 10.1093/bja/aei041. Epub 2004 Nov 26. **PMID:** 15567809 **Citation:** Lundstrom LH, Moller AM, Rosenstock C, Astrup G, Wetterslev J. High body mass index is a weak predictor for difficult and failed tracheal intubation: a cohort study of 91,332 consecutive patients scheduled for direct laryngoscopy registered in the Danish Anesthesia Database. Anesthesiology. 2009 Feb;110(2):266-74. doi: 10.1097/ALN.0b013e318194cac8. **PMID:** 19194154 **Citation:** Heinrich S, Birkholz T, Ihmsen H, Irouschek A, Ackermann A, Schmidt J. Incidence and predictors of difficult laryngoscopy in 11,219 pediatric anesthesia procedures. Paediatr Anaesth. 2012 Aug;22(8):729-36. doi: 10.1111/j.1460-9592.2012.03813.x. Epub 2012 Feb 20. **PMID:** 22340664 **Citation:** Collins JS, Lemmens HJ, Brodsky JB, Brock-Utne JG, Levitan RM. Laryngoscopy and morbid obesity: a comparison of the "sniff" and "ramped" positions. Obes Surg. 2004 Oct;14(9):1171-5. doi: 10.1381/0960892042386869. **PMID:** 15527629 **Citation:** Brodsky JB, Lemmens HJ, Brock-Utne JG, Vierra M, Saidman LJ. Morbid obesity and tracheal intubation. Anesth Analg. 2002 Mar;94(3):732-6; table of contents. doi: 10.1097/00000539-200203000-00047. **PMID:** 11867407 **Citation:** Wilson ME, Spiegelhalter D, Robertson JA, Lesser P. Predicting difficult intubation. Br J Anaesth. 1988 Aug;61(2):211-6. doi: 10.1093/bja/61.2.211. **PMID:** 3415893 **Citation:** Vicini C, De Vito A, Benazzo M, Frassineti S, Campanini A, Frasconi P, Mira E. The nose oropharynx hypopharynx and larynx (NOHL) classification: a new system of diagnostic standardized examination for OSAHS patients. Eur Arch Otorhinolaryngol. 2012 Apr;269(4):1297-300. doi: 10.1007/s00405-012-1965-z. Epub 2012 Feb 19. **PMID:** 22350494 **Citation:** Soares MC, Sallum AC, Goncalves MT, Haddad FL, Gregorio LC. Use of Muller's maneuver in the evaluation of patients with sleep apnea--literature review. Braz J Otorhinolaryngol. 2009 May-Jun;75(3):463-6. doi: 10.1016/S1808-8694(15)30667-4. **PMID:** 19649500 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009765 - Term: Obesity - ID: D000050177 - Term: Overweight - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M12702 - Name: Obesity, Morbid - Relevance: HIGH - As Found: Obesity, Morbid - ID: M26186 - Name: Overweight - Relevance: LOW - As Found: Unknown - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009767 - Term: Obesity, Morbid ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03907579 **Acronym:** S2S **Brief Title:** Screen to Save: A Colorectal Cancer Educational Intervention **Official Title:** Screen to Save: A Colorectal Cancer Educational Intervention #### Organization Study ID Info **ID:** D17190 #### Organization **Class:** OTHER **Full Name:** Dartmouth-Hitchcock Medical Center #### Secondary ID Infos **ID:** P30CA023108-39 **Link:** https://reporter.nih.gov/quickSearch/P30CA023108-39 **Type:** NIH ### Status Module #### Completion Date **Date:** 2017-06-17 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-09-04 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-06-17 **Type:** ACTUAL #### Results First Post Date **Date:** 2020-09-04 **Type:** ACTUAL **Results First Submit Date:** 2020-07-08 **Results First Submit QC Date:** 2020-08-19 #### Start Date **Date:** 2017-03-11 **Type:** ACTUAL **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2019-04-09 **Type:** ACTUAL **Study First Submit Date:** 2019-04-06 **Study First Submit QC Date:** 2019-04-06 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** Dartmouth-Hitchcock Medical Center #### Responsible Party **Investigator Affiliation:** Dartmouth-Hitchcock Medical Center **Investigator Full Name:** Tracy L. Onega **Investigator Title:** Associate Director of Community Outreach and Education, Norris Cotton Cancer Center; Associate Professor, Dartmouth Geisel School of Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this research is to understand if an educational program about colorectal cancer helps improve people's knowledge of colorectal cancer prevention and screening and their intention to get screened for colorectal cancer. ### Conditions Module **Conditions:** - Colorectal Cancer **Keywords:** - Knowledge ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** SCREENING #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants attend a brief educational presentation in an inflatable colon, focused on colorectal cancer prevention and screening. Participants also receive a copy of the study information sheet and may receive written educational materials to take home. Participants complete a pre-test and a post-test to assess changes in knowledge and intention to get screened for colorectal cancer. **Intervention Names:** - Behavioral: Inflatable colon educational module **Label:** Inflatable colon educational module **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Inflatable colon educational module **Description:** Participants attend a brief educational presentation in an inflatable colon, learning about colorectal cancer prevention and screening. **Name:** Inflatable colon educational module **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** A pre-test and post-test is conducted with participants to assess any changes in knowledge related to key learning outcomes expected from the educational intervention (assessed via 14 questions before and after learning). **Measure:** Change in Knowledge Related to Colorectal Cancer Risk, Prevention, and Screening **Time Frame:** Baseline and immediately following intervention **Description:** Post-test conducted to assess behavioral intention related to five prevention and screening behaviors (assessed via 5 questions on a 4-point Likert scale, where a higher score indicates stronger behavioral intention). The scale for all behavioral intention measures started with, "As a result of the colorectal cancer screening information I received during the Screen to Save educational session, I am more likely to..." **Measure:** Number of Participants With Varying Levels of Behavioral Intentions Related to Colorectal Cancer Screening and Prevention **Time Frame:** Immediately following intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age: 50-74 years old * Attendee at event where educational module is offered **Healthy Volunteers:** True **Maximum Age:** 74 Years **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Lebanon **Country:** United States **Facility:** Norris Cotton Cancer Center **State:** New Hampshire **Zip:** 03756 #### Overall Officials **Official 1:** **Affiliation:** Dartmouth College **Name:** Tracy Onega, PhD, MA, MS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** For meta-analyses **Description:** All of the individual de-identified data collected during the trial will be shared with the National Cancer Institute, Geographic Management of Cancer Health Disparities Program (GMaP) contacts, and NCI's designated contractor for the Screen to Save Initiative **Info Types:** - STUDY_PROTOCOL - SAP **IPD Sharing:** YES **Time Frame:** Immediately following data collection events ## Document Section ### Large Document Module #### Large Docs - Date: 2017-12-13 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 402529 - Type Abbrev: Prot - Upload Date: 2020-06-24T15:36 - Date: 2017-03-07 - Filename: ICF_001.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 234840 - Type Abbrev: ICF - Upload Date: 2020-06-24T15:53 - Date: 2020-07-08 - Filename: SAP_002.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 516511 - Type Abbrev: SAP - Upload Date: 2020-07-09T10:55 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007414 - Term: Intestinal Neoplasms - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000003108 - Term: Colonic Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000012002 - Term: Rectal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M17890 - Name: Colorectal Neoplasms - Relevance: HIGH - As Found: Colorectal Cancer - ID: M10448 - Name: Intestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M6336 - Name: Colonic Diseases - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M14844 - Name: Rectal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015179 - Term: Colorectal Neoplasms ### Intervention Browse Module - Browse Branches - Abbrev: HB - Name: Herbal and Botanical - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T120 - Name: Cola - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Inflatable Colon Educational Module **Deaths Num At Risk:** 100 **Description:** Participants attend a brief educational presentation in an inflatable colon, focused on colorectal cancer prevention and screening. Participants also receive a copy of the study information sheet and may receive written educational materials to take home. Participants complete a pre-test and a post-test to assess changes in knowledge and intention to get screened for colorectal cancer. Inflatable colon educational module: Participants attend a brief educational presentation in an inflatable colon, learning about colorectal cancer prevention and screening. **ID:** EG000 **Other Num at Risk:** 100 **Serious Number At Risk:** 100 **Title:** Inflatable Colon Educational Module **Frequency Threshold:** 0 **Time Frame:** During presentation, up to 1 day ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 100 **Units:** Participants ### Group **ID:** BG000 **Title:** Inflatable Colon Educational Module **Description:** Participants attend a brief educational presentation in an inflatable colon, focused on colorectal cancer prevention and screening. Participants also receive a copy of the study information sheet and may receive written educational materials to take home. Participants complete a pre-test and a post-test to assess changes in knowledge and intention to get screened for colorectal cancer. Inflatable colon educational module: Participants attend a brief educational presentation in an inflatable colon, learning about colorectal cancer prevention and screening. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 5.75 **Value:** 59.5 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 98 **Class Title:** Mean age ### Measure #### Measurement **Group ID:** BG000 **Value:** 92 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 8 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 100 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 100 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 100 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 96 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 3 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 100 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 100 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 100 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Spread:** 2.20 **Value:** 10.78 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 100 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Two participants did not provide their age in the baseline survey. **Title:** Age, Customized **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 6 **Description:** Number of correct responses to a series of 14 true/false and multiple-choice test questions about colorectal cancer risks, prevention, and screening. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Correct Answers on Knowledge Questions **Unit of Measure:** correct answers ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** nccc.community.outreach@dartmouth.edu **Organization:** Dartmouth-Hitchcock Norris Cotton Cancer Center **Phone:** 603-653-9960 **Title:** Director of Community Education and Prevention ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0001 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** z= -3.861 **Statistical Method:** Wilcoxon Signed Rank Test **Tested Non-Inferiority:** ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -4 - **Spread:** - **Upper Limit:** 6 - **Value:** 1 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71 **Title:** Strongly agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 **Title:** Agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Disagree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Strongly Disagree **Denomination:** - **Group ID:** OG000 - **Value:** 99 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67 **Title:** Strongly agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30 **Title:** Agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** Disagree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Strongly Disagree **Denomination:** - **Group ID:** OG000 - **Value:** 99 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 64 **Title:** Strongly agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30 **Title:** Agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** Disagree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Strongly Disagree **Denomination:** - **Group ID:** OG000 - **Value:** 98 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 **Title:** Strongly agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 **Title:** Agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Disagree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Strongly Disagree **Denomination:** - **Group ID:** OG000 - **Value:** 99 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70 **Title:** Strongly agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29 **Title:** Agree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** Disagree ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** Strongly Disagree **Denomination:** - **Group ID:** OG000 - **Value:** 100 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** A pre-test and post-test is conducted with participants to assess any changes in knowledge related to key learning outcomes expected from the educational intervention (assessed via 14 questions before and after learning). **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Baseline and immediately following intervention **Title:** Change in Knowledge Related to Colorectal Cancer Risk, Prevention, and Screening **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants attend a brief educational presentation in an inflatable colon, focused on colorectal cancer prevention and screening. Participants also receive a copy of the study information sheet and may receive written educational materials to take home. Participants complete a pre-test and a post-test to assess changes in knowledge and intention to get screened for colorectal cancer. Inflatable colon educational module: Participants attend a brief educational presentation in an inflatable colon, learning about colorectal cancer prevention and screening. **ID:** OG000 **Title:** Inflatable Colon Educational Module #### Outcome Measure 2 **Description:** Post-test conducted to assess behavioral intention related to five prevention and screening behaviors (assessed via 5 questions on a 4-point Likert scale, where a higher score indicates stronger behavioral intention). The scale for all behavioral intention measures started with, "As a result of the colorectal cancer screening information I received during the Screen to Save educational session, I am more likely to..." **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Four intention questions were left blank/unanswered by one to two participants each. **Reporting Status:** POSTED **Time Frame:** Immediately following intervention **Title:** Number of Participants With Varying Levels of Behavioral Intentions Related to Colorectal Cancer Screening and Prevention **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants attend a brief educational presentation in an inflatable colon, focused on colorectal cancer prevention and screening. Participants also receive a copy of the study information sheet and may receive written educational materials to take home. Participants complete a pre-test and a post-test to assess changes in knowledge and intention to get screened for colorectal cancer. Inflatable colon educational module: Participants attend a brief educational presentation in an inflatable colon, learning about colorectal cancer prevention and screening. **ID:** OG000 **Title:** Inflatable Colon Educational Module ### Participant Flow Module #### Group **Description:** Participants attend a brief educational presentation in an inflatable colon, focused on colorectal cancer prevention and screening. Participants also receive a copy of the study information sheet and may receive written educational materials to take home. Participants complete a pre-test and a post-test to assess changes in knowledge and intention to get screened for colorectal cancer. Inflatable colon educational module: Participants attend a brief educational presentation in an inflatable colon, learning about colorectal cancer prevention and screening. **ID:** FG000 **Title:** Inflatable Colon Educational Module #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 100 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 100 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02283879 **Brief Title:** Human Umbilical Cord Mesenchymal Stem Cell in Cerebral Hemorrhage Sequela **Official Title:** Human Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Cerebral Hemorrhage #### Organization Study ID Info **ID:** HYK-Cerebral hemorrhage #### Organization **Class:** INDUSTRY **Full Name:** Shenzhen Hornetcorn Bio-technology Company, LTD ### Status Module #### Completion Date **Date:** 2017-04 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2016-05-24 **Type:** ESTIMATED **Last Update Submit Date:** 2016-05-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-12 **Type:** ESTIMATED #### Start Date **Date:** 2015-03 **Status Verified Date:** 2015-07 #### Study First Post Date **Date:** 2014-11-05 **Type:** ESTIMATED **Study First Submit Date:** 2014-11-03 **Study First Submit QC Date:** 2014-11-03 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Fifth Affiliated Hospital of Guangzhou Medical University #### Lead Sponsor **Class:** INDUSTRY **Name:** Shenzhen Hornetcorn Bio-technology Company, LTD #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to evaluate the safety and efficacy of human umbilical cord mesenchymal stem cell(hUC-MSC) for cerebral hemorrhage sequela. **Detailed Description:** Human umbilical cord mesenchymal stem cells exhibit the potential to differentiate into neural cells, which have been confirmed in in vivo and in vitro experiments. There have been few clinical reports describing umbilical cord mesenchymal stem cells for treatment of cerebral hemorrhage. To investigate the effects of hUC-MSC treatment for cerebral hemorrhage sequela, 20 patients with cerebral hemorrhage will be enrolled and receive 4 times of hUC-MSC transplantation. ### Conditions Module **Conditions:** - Cerebral Hemorrhage **Keywords:** - Human Umbilical Cord Mesenchymal Stem Cell - Mesenchymal Stem Cell - Cerebral hemorrhage ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will receive human umbilical cord mesenchymal stem cells transplantation with a 12 months follow-up. **Intervention Names:** - Biological: Human umbilical cord mesenchymal stem cells **Label:** hUC-MSC treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - hUC-MSC treatment **Description:** A single dose of 2×107 hUC-MSC will treated to patients, IV, Repeat every weeks for four times. **Name:** Human umbilical cord mesenchymal stem cells **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Safety evaluation through vital signs, the results of clinical lab tests and adverse events (AEs) **Time Frame:** 12 months #### Secondary Outcomes **Measure:** Improvement of infarct size measured by brain MRI **Time Frame:** before the transplant and 1, 6, 12 months after transplantation **Measure:** Modified Barthel index **Time Frame:** before and 1, 3, 6 and 12 months after transplantation **Measure:** National Institutes of Health stroke scale(NIHSS) score **Time Frame:** before the transplant and after the transplant 1, 2 and 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 40-70 intracerebral hemorrhage patient * With stroke history of more than 3 months, less than 60 months * National Institutes of Health stroke scale(NIHSS) score of 7 or more points * Patient is stable (normal respiration, afebrile, BP less than mean arterial pressure of 125 mm of Hg, fasting blood sugar \<7 mg, and normal urea/electrolytes for at least 48 hours.) Exclusion Criteria: * History of neurological disease, head injury or psychiatric disorder; * Pregnant women; * Impaired liver function, abnormal blood coagulation, AIDS, HIV, combine other tumor or special condition; * Progressive apoplexy; * With malignant tumors. **Maximum Age:** 80 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Guangzhou **Country:** China **Facility:** The Fifth Affiliated Hospital Immunotherapy center **State:** Guangdong **Zip:** 510000 #### Overall Officials **Official 1:** **Affiliation:** Fifth Affiliated Hospital of Guangzhou Medical University **Name:** Ping J Chen, Professor **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020300 - Term: Intracranial Hemorrhages - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5792 - Name: Cerebral Hemorrhage - Relevance: HIGH - As Found: Cerebral Hemorrhage - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M22113 - Name: Intracranial Hemorrhages - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002543 - Term: Cerebral Hemorrhage - ID: D000006470 - Term: Hemorrhage ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02763579 **Acronym:** IMpower133 **Brief Title:** A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) **Official Title:** A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer #### Organization Study ID Info **ID:** GO30081 #### Organization **Class:** INDUSTRY **Full Name:** Hoffmann-La Roche #### Secondary ID Infos **ID:** 2015-004861-97 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2022-07-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-04-24 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-06-13 **Type:** ACTUAL **Results First Submit Date:** 2019-04-19 **Results First Submit QC Date:** 2019-05-21 #### Start Date **Date:** 2016-06-07 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2016-05-05 **Type:** ESTIMATED **Study First Submit Date:** 2016-05-04 **Study First Submit QC Date:** 2016-05-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This randomized, Phase I/III, multicenter, double-blinded, placebo-controlled study was designed to evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 \[PD-L1\] antibody) in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC. Participants will be randomized in a 1:1 ratio to receive either atezolizumab + carboplatin + etoposide or placebo + carboplatin + etoposide on 21-day cycles for four cycles in the induction phase followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration. ### Conditions Module **Conditions:** - Small Cell Lung Carcinoma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 503 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **Intervention Names:** - Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody - Drug: Carboplatin - Drug: Etoposide **Label:** Atezolizumab + Carboplatin + Etoposide **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **Intervention Names:** - Drug: Carboplatin - Drug: Etoposide - Drug: Placebo **Label:** Placebo + Carboplatin + Etoposide **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Atezolizumab + Carboplatin + Etoposide **Description:** Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward). **Name:** Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody **Other Names:** - MPDL3280A, RO5541267, Tecentriq **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Atezolizumab + Carboplatin + Etoposide - Placebo + Carboplatin + Etoposide **Description:** Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4). **Name:** Carboplatin **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Atezolizumab + Carboplatin + Etoposide - Placebo + Carboplatin + Etoposide **Description:** Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4). **Name:** Etoposide **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Placebo + Carboplatin + Etoposide **Description:** Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward). **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s). **Measure:** Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population **Time Frame:** Baseline until PD or death, whichever occurs first (up to approximately 23 months) **Description:** OS is defined as the time from randomization to death from any cause. **Measure:** Duration of Overall Survival (OS) in the Global Population **Time Frame:** Baseline until death from any cause (up to approximately 23 months) #### Secondary Outcomes **Description:** Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1. **Measure:** Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population **Time Frame:** Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months) **Description:** DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first. **Measure:** Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population **Time Frame:** First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months) **Description:** PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively. **Measure:** PFS Rate at 6 Months and at 1 Year in Global Population **Time Frame:** 6 months, 1 year **Description:** OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively. **Measure:** OS Rate at 1 Year and 2 Years in the Global Population **Time Frame:** 1 year, 2 years **Description:** TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant. **Measure:** Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population **Time Frame:** Baseline until deterioration per symptom subscale (up to approximately 23 months) **Description:** The percentage of participants with at least one adverse event in the global population. **Measure:** Percentage of Participants With at Least One Adverse Event in the Global Population **Time Frame:** Baseline until up to 90 days after end of treatment (up to approximately 49 months) **Description:** The baseline prevalence and post-baseline incidence of ADAs against atezolizumab. **Measure:** Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population **Time Frame:** Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall) **Description:** Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day. **Measure:** Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population **Time Frame:** Post-dose Day 1 of Cycle 1 (cycle length = 21 days) **Description:** Atezolizumab pre-dose plasma concentration (Cmin) for each respective day. **Measure:** Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population **Time Frame:** Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days) **Description:** Plasma concentration of carboplatin in the Global population. **Measure:** Plasma Concentration of Carboplatin in the Global Population **Time Frame:** Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days) **Description:** Plasma concentration of etoposide in the Global Population. **Measure:** Plasma Concentration of Etoposide in the Global Population **Time Frame:** Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group \[VALG\] staging system) * No prior systemic treatment for ES-SCLC * Eastern Cooperative Oncology Group performance status of 0 or 1 * Measurable disease, as defined by RECIST v1.1 * Adequate hematologic and end organ function * Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC Exclusion Criteria: * Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation * Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome * Pregnant or lactating women * History of autoimmune disease * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * Positive test result for human immunodeficiency virus (HIV) * Active hepatitis B or hepatitis C * Severe infections at the time of randomization * Significant cardiovascular disease * Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody * History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Fort Myers **Country:** United States **Facility:** Florida Cancer Specialists - Fort Myers (Broadway) **State:** Florida **Zip:** 33901 **Location 2:** **City:** Orlando **Country:** United States **Facility:** Florida Hospital **State:** Florida **Zip:** 32804 **Location 3:** **City:** Saint Petersburg **Country:** United States **Facility:** Florida Cancer Specialists. **State:** Florida **Zip:** 33705 **Location 4:** **City:** Marietta **Country:** United States **Facility:** Northwest Georgia Oncology Centers PC - Marietta **State:** Georgia **Zip:** 30060 **Location 5:** **City:** Chicago **Country:** United States **Facility:** Rush University Medical Center **State:** Illinois **Zip:** 60612-3244 **Location 6:** **City:** Peoria **Country:** United States **Facility:** Illinois Cancer Care **State:** Illinois **Zip:** 61615 **Location 7:** **City:** Zion **Country:** United States **Facility:** Cancer Treatment Centers of America - Midwestern Regional Medical Center **State:** Illinois **Zip:** 60099 **Location 8:** **City:** Louisville **Country:** United States **Facility:** Louisville Oncology **State:** Kentucky **Zip:** 40202 **Location 9:** **City:** Scarborough **Country:** United States **Facility:** New England Cancer Specialists **State:** Maine **Zip:** 04074 **Location 10:** **City:** Baltimore **Country:** United States **Facility:** Weinberg CA Inst Franklin Sq **State:** Maryland **Zip:** 21237 **Location 11:** **City:** Rochester **Country:** United States **Facility:** Mayo Clinic **State:** Minnesota **Zip:** 55905 **Location 12:** **City:** Las Vegas **Country:** United States **Facility:** Comprehensive Cancer Centers of Nevada - Eastern Avenue **State:** Nevada **Zip:** 89169 **Location 13:** **City:** Paramus **Country:** United States **Facility:** The Valley Hospital **State:** New Jersey **Zip:** 07652 **Location 14:** **City:** Binghamton **Country:** United States **Facility:** Broome Oncology - Binghamton **State:** New York **Zip:** 13905 **Location 15:** **City:** Charlotte **Country:** United States **Facility:** Levine Cancer Institute **State:** North Carolina **Zip:** 28204 **Location 16:** **City:** Chattanooga **Country:** United States **Facility:** Tennessee Oncology Chattanooga **State:** Tennessee **Zip:** 37404 **Location 17:** **City:** Nashville **Country:** United States **Facility:** Tennessee Oncology PLLC - Nashville (20th Ave) **State:** Tennessee **Zip:** 37203 **Location 18:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt Medical Center **State:** Tennessee **Zip:** 37232-7610 **Location 19:** **City:** Fairfax **Country:** United States **Facility:** Virginia Cancer Specialists, PC **State:** Virginia **Zip:** 22031 **Location 20:** **City:** Roanoke **Country:** United States **Facility:** Blue Ridge Cancer Care **State:** Virginia **Zip:** 24014 **Location 21:** **City:** Tacoma **Country:** United States **Facility:** Northwest Medical Specialties **State:** Washington **Zip:** 98405 **Location 22:** **City:** Madison **Country:** United States **Facility:** University of Wisconsin **State:** Wisconsin **Zip:** 53705 **Location 23:** **City:** Camperdown **Country:** Australia **Facility:** Chris O'Brien Lifehouse **State:** New South Wales **Zip:** 2050 **Location 24:** **City:** Chermside **Country:** Australia **Facility:** The Prince Charles Hospital; Oncology Dept. **State:** Queensland **Zip:** 4032 **Location 25:** **City:** Parkville **Country:** Australia **Facility:** Royal Melbourne Hospital; Hematology and Medical Oncology **State:** Victoria **Zip:** 3052 **Location 26:** **City:** Linz **Country:** Austria **Facility:** Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten **Zip:** 4020 **Location 27:** **City:** Salzburg **Country:** Austria **Facility:** Salzburger Landeskliniken; Universitätsklinik für Pneumologie/ Lungenheilkunde **Zip:** 5020 **Location 28:** **City:** Wien **Country:** Austria **Facility:** Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten **Zip:** 1140 **Location 29:** **City:** Wien **Country:** Austria **Facility:** Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie **Zip:** 1210 **Location 30:** **City:** Salvador **Country:** Brazil **Facility:** Santa Casa de Misericordia de Salvador **State:** BA **Zip:** 40050-410 **Location 31:** **City:** Lajeado **Country:** Brazil **Facility:** Hospital Bruno Born **State:** RS **Zip:** 95900-000 **Location 32:** **City:** Porto Alegre **Country:** Brazil **Facility:** Hospital das Clinicas - UFRGS **State:** RS **Zip:** 90035-903 **Location 33:** **City:** Sao Paulo **Country:** Brazil **Facility:** Instituto do Cancer do Estado de Sao Paulo - ICESP **State:** SP **Zip:** 01246-000 **Location 34:** **City:** Recoleta **Country:** Chile **Facility:** Bradford Hill Centro de Investigaciones Clinicas **Zip:** 8420383 **Location 35:** **City:** Santiago **Country:** Chile **Facility:** OrlandiOncología **Zip:** 7500713 **Location 36:** **City:** Beijing **Country:** China **Facility:** Beijing Cancer Hospital **Zip:** 100142 **Location 37:** **City:** Changchun **Country:** China **Facility:** Jilin Cancer Hospital **Zip:** 132013 **Location 38:** **City:** Guangzhou **Country:** China **Facility:** The First Affiliated Hospital of Guangzhou Medical University **Zip:** 510120 **Location 39:** **City:** Harbin **Country:** China **Facility:** Harbin Medical University Cancer Hospital **Zip:** 150081 **Location 40:** **City:** Nanjing City **Country:** China **Facility:** Jiangsu Cancer Hospital **Zip:** 211100 **Location 41:** **City:** Shanghai City **Country:** China **Facility:** Fudan University Shanghai Cancer Center **Zip:** 200120 **Location 42:** **City:** Shanghai **Country:** China **Facility:** Zhongshan Hospital Fudan University **Zip:** 200032 **Location 43:** **City:** Zhejiang **Country:** China **Facility:** Zhejiang Cancer Hospital **Zip:** 310022 **Location 44:** **City:** Zhengzhou **Country:** China **Facility:** Henan Cancer Hospital **Zip:** 450008 **Location 45:** **City:** Olomouc **Country:** Czechia **Facility:** Fakultni nemocnice Olomouc **Zip:** 779 00 **Location 46:** **City:** Praha 4 - Krc **Country:** Czechia **Facility:** Thomayerova nemocnice **Zip:** 140 59 **Location 47:** **City:** Praha 8 **Country:** Czechia **Facility:** Fakultni nemocnice Na Bulovce **Zip:** 180 81 **Location 48:** **City:** Bordeaux **Country:** France **Facility:** Institut Bergonie; Oncologie **Zip:** 33076 **Location 49:** **City:** Caen **Country:** France **Facility:** Centre Francois Baclesse; Oncologie **Zip:** 14076 **Location 50:** **City:** Lille **Country:** France **Facility:** Hopital Calmette; Pneumologie Oncologie Ouest **Zip:** 59037 **Location 51:** **City:** Marseille **Country:** France **Facility:** Hôpital Nord - AP-HM Marseille# **Zip:** 13915 **Location 52:** **City:** Gauting **Country:** Germany **Facility:** Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie **Zip:** 82131 **Location 53:** **City:** Großhansdorf **Country:** Germany **Facility:** LungenClinic Großhansdorf GmbH **Zip:** 22927 **Location 54:** **City:** Halle **Country:** Germany **Facility:** Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II **Zip:** 06120 **Location 55:** **City:** Heidelberg **Country:** Germany **Facility:** Thoraxklinik Heidelberg gGmbH **Zip:** 69126 **Location 56:** **City:** Immenhausen **Country:** Germany **Facility:** Fachklinik für Lungenerkrankungen **Zip:** 34376 **Location 57:** **City:** Athens **Country:** Greece **Facility:** Sotiria Chest Hospital of Athens **Zip:** 11527 **Location 58:** **City:** Athens **Country:** Greece **Facility:** Agioi Anargyroi; 3Rd Dept. of Medical Oncology **Zip:** 145 64 **Location 59:** **City:** Patras **Country:** Greece **Facility:** University Hospital of Patras Medical Oncology **Zip:** 265 04 **Location 60:** **City:** Budapest **Country:** Hungary **Facility:** Semmelweis Egyetem, AOK, Pulmonologiai Klinika **Zip:** 1083 **Location 61:** **City:** Budapest **Country:** Hungary **Facility:** Orszagos Koranyi TBC es Pulmonologiai Intezet **Zip:** 1121 **Location 62:** **City:** Debrecen **Country:** Hungary **Facility:** Debreceni Egyetem, Klinikai Kozpont, Tudogyogyaszati Klinika **Zip:** 4032 **Location 63:** **City:** Torokbalint **Country:** Hungary **Facility:** Tudogyogyintezet Torokbalint **Zip:** 2045 **Location 64:** **City:** Parma **Country:** Italy **Facility:** A.O. Universitaria Di Parma **State:** Emilia-Romagna **Zip:** 43100 **Location 65:** **City:** Roma **Country:** Italy **Facility:** Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica **State:** Lazio **Zip:** 00128 **Location 66:** **City:** Milano **Country:** Italy **Facility:** Fondazione IRCCS Istituto Nazionale dei Tumori **State:** Lombardia **Zip:** 20133 **Location 67:** **City:** Milano **Country:** Italy **Facility:** Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia **State:** Lombardia **Zip:** 20141 **Location 68:** **City:** San Giovanni Rotondo **Country:** Italy **Facility:** IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia **State:** Puglia **Zip:** 71013 **Location 69:** **City:** Pisa **Country:** Italy **Facility:** Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare **State:** Toscana **Zip:** 56124 **Location 70:** **City:** Fukuoka **Country:** Japan **Facility:** Kyushu University Hospital; Respiratory **Zip:** 812-8582 **Location 71:** **City:** Hyogo **Country:** Japan **Facility:** National Hospital Organization Himeji Medical Center **Zip:** 670-8520 **Location 72:** **City:** Kanagawa **Country:** Japan **Facility:** Kanagawa Cancer Center;Thoracic Oncology **Zip:** 241-8515 **Location 73:** **City:** Kyoto **Country:** Japan **Facility:** University Hospital Kyoto Prefectural University of Medicine,?Pulmonary Medicine **Zip:** 602-8566 **Location 74:** **City:** Miyagi **Country:** Japan **Facility:** Sendai Kousei Hospital; Pulmonary Medicine **Zip:** 980-0873 **Location 75:** **City:** Okayama **Country:** Japan **Facility:** Kurashiki Central Hospital; Respiratory Medicine **Zip:** 710-8602 **Location 76:** **City:** Osaka **Country:** Japan **Facility:** Kindai University Hospital; Medical Oncology **Zip:** 589-8511 **Location 77:** **City:** Osaka **Country:** Japan **Facility:** National Hospital Organization Kinki-Chuo Chest Medical Center; Internal Medicine **Zip:** 591-8555 **Location 78:** **City:** Satima **Country:** Japan **Facility:** Saitama Cancer Center; Thoracic Oncology **Zip:** 362-0806 **Location 79:** **City:** Shizuoka **Country:** Japan **Facility:** Shizuoka Cancer Center; Thoracic Oncology **Zip:** 411-8777 **Location 80:** **City:** Tokyo **Country:** Japan **Facility:** Tokyo Metropolitan Komagome Hospital; Thoracic Oncology and Respiratory Medicine **Zip:** 113-8677 **Location 81:** **City:** Tokyo **Country:** Japan **Facility:** The Cancer Institute Hospital of JFCR, Respiratory Medicine **Zip:** 135-8550 **Location 82:** **City:** Wakayama **Country:** Japan **Facility:** Wakayama Medical University Hospital; Respiratory Medicine and Medical Oncology **Zip:** 641-8509 **Location 83:** **City:** Seongnam-si **Country:** Korea, Republic of **Facility:** Seoul National University Bundang Hospital **Zip:** 463-707 **Location 84:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Seoul National University Hospital **Zip:** 03080 **Location 85:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Asan Medical Center **Zip:** 05505 **Location 86:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Samsung Medical Center **Zip:** 135-710 **Location 87:** **City:** Cdmx **Country:** Mexico **Facility:** Health Pharma Professional Research **State:** Mexico CITY (federal District) **Zip:** 03100 **Location 88:** **City:** Gdansk **Country:** Poland **Facility:** Medical University of Gdansk **Zip:** 80-952 **Location 89:** **City:** Lodz **Country:** Poland **Facility:** Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi **Zip:** 93-513 **Location 90:** **City:** Olsztyn **Country:** Poland **Facility:** Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc; Oddzial V Chemioterapii Nowotworow Pluc **Zip:** 10-357 **Location 91:** **City:** Otwock **Country:** Poland **Facility:** Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy **Zip:** 05-400 **Location 92:** **City:** Poznan **Country:** Poland **Facility:** Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu **Zip:** 60-569 **Location 93:** **City:** Warszawa **Country:** Poland **Facility:** Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology **Zip:** 02-781 **Location 94:** **City:** Moscovskaya Oblast **Country:** Russian Federation **Facility:** Moscow City Oncology Hospital #62 **State:** Moskovskaja Oblast **Zip:** 143423 **Location 95:** **City:** Moscow **Country:** Russian Federation **Facility:** N.N.Burdenko Main Military Clinical Hospital; Oncology Dept **State:** Moskovskaja Oblast **Zip:** 105229 **Location 96:** **City:** Moscow **Country:** Russian Federation **Facility:** Russian Oncology Research Center n.a. N.N. Blokhin **State:** Moskovskaja Oblast **Zip:** 115478 **Location 97:** **City:** Sankt-peterburg **Country:** Russian Federation **Facility:** City Clinical Onc. **State:** Sankt Petersburg **Zip:** 198255 **Location 98:** **City:** St. Petersburg **Country:** Russian Federation **Facility:** Scientific Research Oncology Institute named after N.N. Petrov; Oncology **State:** Sankt Petersburg **Zip:** 197758 **Location 99:** **City:** Novosibirsk **Country:** Russian Federation **Facility:** City Clinical Hospital No. 1 **Zip:** 630047 **Location 100:** **City:** Belgrade **Country:** Serbia **Facility:** Clinical Center of Serbia **Zip:** 11000 **Location 101:** **City:** Nis **Country:** Serbia **Facility:** Clinical Center Nis; Clinic for pulmonary diseases **Zip:** 18 000 **Location 102:** **City:** Sant Andreu de La Barca **Country:** Spain **Facility:** Hospital Univ Vall d'Hebron; Servicio de Oncologia **State:** Barcelona **Zip:** 08740 **Location 103:** **City:** Madrid **Country:** Spain **Facility:** Hospital Ramon y Cajal; Servicio de Oncologia **Zip:** 28034 **Location 104:** **City:** Madrid **Country:** Spain **Facility:** Hospital Universitario La Paz; Servicio de Oncologia **Zip:** 28046 **Location 105:** **City:** Malaga **Country:** Spain **Facility:** Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia **Zip:** 29010 **Location 106:** **City:** Sevilla **Country:** Spain **Facility:** Hospital Universitario Virgen del Rocio; Servicio de Oncologia **Zip:** 41013 **Location 107:** **City:** Zaragoza **Country:** Spain **Facility:** Hosp Clinico Univ Lozano Blesa; División De Oncología Médica **Zip:** 50009 **Location 108:** **City:** Taipei **Country:** Taiwan **Facility:** National Taiwan Uni Hospital; Internal Medicine **Zip:** 100 **Location 109:** **City:** Taipei **Country:** Taiwan **Facility:** Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology **Zip:** 112 **Location 110:** **City:** Taoyuan **Country:** Taiwan **Facility:** Chang Gung Medical Foundation - Linkou; Chest Dept **Zip:** 333 **Location 111:** **City:** Exeter **Country:** United Kingdom **Facility:** Royal Devon & Exeter Hospital; Oncology Centre **Zip:** EX2 5DW **Location 112:** **City:** London **Country:** United Kingdom **Facility:** Barts and the London NHS Trust. **Zip:** EC1A 7BE **Location 113:** **City:** London **Country:** United Kingdom **Facility:** Guys and St Thomas NHS Foundation Trust, Guys Hospital **Zip:** SE1 9RT **Location 114:** **City:** Manchester **Country:** United Kingdom **Facility:** Christie Hospital Nhs Trust; Medical Oncology **Zip:** M2O 4BX #### Overall Officials **Official 1:** **Affiliation:** Hoffmann-La Roche **Name:** Clinical Trials **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13. **PMID:** 33439693 **Citation:** Mansfield AS, Kazarnowicz A, Karaseva N, Sanchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. doi: 10.1016/j.annonc.2019.10.021. Epub 2019 Dec 9. **PMID:** 31959349 **Citation:** Nishio M, Sugawara S, Atagi S, Akamatsu H, Sakai H, Okamoto I, Takayama K, Hayashi H, Nakagawa Y, Kawakami T. Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Clin Lung Cancer. 2019 Nov;20(6):469-476.e1. doi: 10.1016/j.cllc.2019.07.005. Epub 2019 Jul 31. **PMID:** 31466854 **Citation:** Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25. **PMID:** 30280641 ## Document Section ### Large Document Module #### Large Docs - Date: 2019-03-06 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 4423710 - Type Abbrev: Prot_SAP - Upload Date: 2019-05-21T12:32 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms - ID: D000008175 - Term: Lung Neoplasms - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M11172 - Name: Lung Neoplasms - Relevance: LOW - As Found: Unknown - ID: M28323 - Name: Small Cell Lung Carcinoma - Relevance: HIGH - As Found: Small Cell Lung Carcinoma - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T5271 - Name: Small Cell Lung Cancer - Relevance: HIGH - As Found: Small Cell Lung Cancer ### Condition Browse Module - Meshes - ID: D000055752 - Term: Small Cell Lung Carcinoma ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000972 - Term: Antineoplastic Agents, Phytogenic - ID: D000059005 - Term: Topoisomerase II Inhibitors - ID: D000059003 - Term: Topoisomerase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000082082 - Term: Immune Checkpoint Inhibitors - ID: D000074322 - Term: Antineoplastic Agents, Immunological ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: HIGH - As Found: Program - ID: M18650 - Name: Carboplatin - Relevance: HIGH - As Found: System - ID: M8191 - Name: Etoposide - Relevance: HIGH - As Found: Tolerability - ID: M349417 - Name: Atezolizumab - Relevance: HIGH - As Found: Pemetrexed - ID: M341643 - Name: Etoposide phosphate - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: HIGH - As Found: Pemetrexed - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016190 - Term: Carboplatin - ID: D000005047 - Term: Etoposide - ID: C000594389 - Term: Atezolizumab - ID: D000000906 - Term: Antibodies - ID: D000000911 - Term: Antibodies, Monoclonal ### Misc Info Module #### Removed Countries - Country: Czech Republic - Country: Hong Kong - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious \& other adverse events reported based on safety population, which included participants who received any amount of any component of study treatment. #### Event Groups **Group ID:** EG000 **Title:** Placebo + Carboplatin + Etoposide - Global **Deaths Num Affected:** 11 **Deaths Num At Risk:** 196 **Description:** Participants in the Global population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** EG000 **Other Num Affected:** 187 **Other Num at Risk:** 196 **Serious Number Affected:** 69 **Serious Number At Risk:** 196 **Title:** Placebo + Carboplatin + Etoposide - Global **Group ID:** EG001 **Title:** Atezolizumab + Carboplatin + Etoposide - Global **Deaths Num Affected:** 5 **Deaths Num At Risk:** 198 **Description:** Participants in the Global population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** EG001 **Other Num Affected:** 191 **Other Num at Risk:** 198 **Serious Number Affected:** 81 **Serious Number At Risk:** 198 **Title:** Atezolizumab + Carboplatin + Etoposide - Global **Group ID:** EG002 **Title:** Placebo + Carboplatin + Etoposide - China **Deaths Num Affected:** 1 **Deaths Num At Risk:** 52 **Description:** Participants in the China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** EG002 **Other Num Affected:** 52 **Other Num at Risk:** 52 **Serious Number Affected:** 14 **Serious Number At Risk:** 52 **Title:** Placebo + Carboplatin + Etoposide - China **Group ID:** EG003 **Title:** Atezolizumab + Carboplatin + Etoposide - China **Deaths Num Affected:** 3 **Deaths Num At Risk:** 57 **Description:** Participants in the China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** EG003 **Other Num Affected:** 56 **Other Num at Risk:** 57 **Serious Number Affected:** 22 **Serious Number At Risk:** 57 **Title:** Atezolizumab + Carboplatin + Etoposide - China **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Leukopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Sinus tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hyperthyroidism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypothyroidism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Abdominal distension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Stomatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Asthenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Chest discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hepatic function abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Blood alkaline phosphatase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Blood bilirubin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Blood cholesterol increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Blood creatinine increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Blood glucose increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Blood triglycerides increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Electrocardiogram QT prolonged **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Gamma-glutamyltransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Haemoglobin decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Platelet count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Protein urine present **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Weight decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Weight increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** White blood cell count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hyperglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypertriglyceridaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypoalbuminaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypochloraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypomagnesaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypoproteinaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Proteinuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Haemoptysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Oropharyngeal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Productive cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Rash maculo-papular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 25.0 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 25.0 #### Serious Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 198 **Num Events:** 4 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Disseminated intravascular coagulation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Febrile neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 9 **Num At Risk:** 196 **Num Events:** 9 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 198 **Num Events:** 5 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 52 **Num Events:** 2 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Granulocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Leukocytosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Leukopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Myelosuppression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 8 **Num At Risk:** 196 **Num Events:** 8 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 198 **Num Events:** 7 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Pancytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 196 **Num Events:** 4 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 196 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 198 **Num Events:** 5 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 52 **Num Events:** 2 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Atrial fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 196 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Atrioventricular block complete **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cardiac failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cardiac tamponade **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cardiopulmonary failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Coronary artery disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pericardial effusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Supraventricular tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Autoimmune thyroiditis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Inappropriate antidiuretic hormone secretion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Abdominal adhesions **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Autoimmune colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 198 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Diverticular perforation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Faeces discoloured **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Gastric ulcer perforation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Gastritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Ileus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Intestinal obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Lip oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pancreatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 3 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pancreatitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Proctitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Small intestinal obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 196 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 198 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Asthenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Chest discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 57 **Num Events:** 2 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 198 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** General physical health deterioration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Influenza like illness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Systemic inflammatory response syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cholangitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Drug-induced liver injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Jaundice **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Clostridium difficile colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Clostridium difficile infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cytomegalovirus infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Device related sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Lower respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Lung abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Myelitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Neutropenic sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 10 **Num At Risk:** 196 **Num Events:** 11 **Group ID:** EG001 **Num Affected:** 12 **Num At Risk:** 198 **Num Events:** 15 **Group ID:** EG002 **Num Affected:** 4 **Num At Risk:** 52 **Num Events:** 5 **Group ID:** EG003 **Num Affected:** 4 **Num At Risk:** 57 **Num Events:** 7 **Term:** Pulmonary sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pyopneumothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Septic shock **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Femur fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Head injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Limb injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Radiation oesophagitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Thoracic vertebral fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Blood alkaline phosphatase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Blood bilirubin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Blood creatinine increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** C-reactive protein increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Liver function test increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 2 **Num At Risk:** 52 **Num Events:** 2 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 57 **Num Events:** 2 **Term:** Platelet count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num Affected:** 4 **Num At Risk:** 57 **Num Events:** 4 **Term:** Transaminases increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** White blood cell count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Electrolyte imbalance **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Hyperglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Hypokalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Hypomagnesaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Hyponatraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 196 **Num Events:** 4 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Muscular weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Metastatic neoplasm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Paraneoplastic syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Plasma cell myeloma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Tumour pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cerebral infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Dysarthria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Guillain-Barre syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Neuropathy peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Somnolence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Spinal cord oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 198 **Num Events:** 3 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Transient ischaemic attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Trigeminal neuralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Alcohol abuse **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Tubulointerstitial nephritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Acute respiratory failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Asthma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Bronchial obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Chronic obstructive pulmonary disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Haemoptysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Hypercapnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pleural effusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 2 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pneumonitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 198 **Num Events:** 4 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 57 **Num Events:** 2 **Term:** Pneumothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pulmonary embolism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 196 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Pulmonary oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Respiratory failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 57 **Num Events:** 1 **Term:** Skin toxicity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Peripheral arterial occlusive disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Peripheral artery occlusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 196 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 198 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Superior vena cava syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Term:** Venous thrombosis limb **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 25.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 196 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 198 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 52 **Group ID:** EG003 **Num At Risk:** 57 **Time Frame:** From the first study drug administration to the data cutoff date: 7 July 2022 (up to 49 months). ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 251 **Group ID:** BG001 **Value:** 252 **Group ID:** BG002 **Value:** 503 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo + Carboplatin + Etoposide - All **Description:** All participants in the Global or China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. ### Group **ID:** BG001 **Title:** Atezolizumab + Carboplatin + Etoposide - All **Description:** All participants in the Global or China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.0 **Value:** 63.6 #### Measurement **Group ID:** BG001 **Spread:** 8.8 **Value:** 63.8 #### Measurement **Group ID:** BG002 **Spread:** 8.9 **Value:** 63.7 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 202 **Group ID:** BG001 **Value:** 201 **Group ID:** BG002 **Value:** 403 **Class Title:** Global #### Measurement **Group ID:** BG000 **Spread:** 8.8 **Value:** 60.7 #### Measurement **Group ID:** BG001 **Spread:** 9.0 **Value:** 59.7 #### Measurement **Group ID:** BG002 **Spread:** 8.9 **Value:** 60.2 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 53 **Group ID:** BG001 **Value:** 57 **Group ID:** BG002 **Value:** 110 **Class Title:** China ### Measure #### Measurement **Group ID:** BG000 **Value:** 70 #### Measurement **Group ID:** BG001 **Value:** 72 #### Measurement **Group ID:** BG002 **Value:** 142 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 132 #### Measurement **Group ID:** BG001 **Value:** 129 #### Measurement **Group ID:** BG002 **Value:** 261 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 202 **Group ID:** BG001 **Value:** 201 **Group ID:** BG002 **Value:** 403 **Class Title:** Global #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 23 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 41 #### Measurement **Group ID:** BG001 **Value:** 46 #### Measurement **Group ID:** BG002 **Value:** 87 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 53 **Group ID:** BG001 **Value:** 57 **Group ID:** BG002 **Value:** 110 **Class Title:** China ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 16 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 185 #### Measurement **Group ID:** BG001 **Value:** 187 #### Measurement **Group ID:** BG002 **Value:** 372 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 15 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 202 **Group ID:** BG001 **Value:** 201 **Group ID:** BG002 **Value:** 403 **Class Title:** Global #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 53 #### Measurement **Group ID:** BG001 **Value:** 57 #### Measurement **Group ID:** BG002 **Value:** 110 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 53 **Group ID:** BG001 **Value:** 57 **Group ID:** BG002 **Value:** 110 **Class Title:** China ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 36 #### Measurement **Group ID:** BG001 **Value:** 33 #### Measurement **Group ID:** BG002 **Value:** 69 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 159 #### Measurement **Group ID:** BG001 **Value:** 163 #### Measurement **Group ID:** BG002 **Value:** 322 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 8 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 202 **Group ID:** BG001 **Value:** 201 **Group ID:** BG002 **Value:** 403 **Class Title:** Global #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 53 #### Measurement **Group ID:** BG001 **Value:** 57 #### Measurement **Group ID:** BG002 **Value:** 110 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 53 **Group ID:** BG001 **Value:** 57 **Group ID:** BG002 **Value:** 110 **Class Title:** China **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension. **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Description:** As reported from Electronic Case Report Form (eCRF). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The Global population included 403 participants. The China population included 100 participants enrolled during the China Extension plus 10 Chinese participants from the Global population. **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension. **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension. **Title:** Race (NIH/OMB) **Unit of Measure:** Participants **Population Description:** The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension. Separate analyses were performed for the Global population and the China population in the study. ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** genentech@druginfo.com **Organization:** Hoffmann-La Roche **Phone:** 800-821-8590 **Title:** Medical Communications ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.62 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.96 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0170 **P-Value Comment:** **Parameter Type:** Stratified Hazard Ratio **Parameter Value:** 0.77 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 0.54 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.91 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0069 **P-Value Comment:** **Parameter Type:** Stratified Hazard Ratio **Parameter Value:** 0.70 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 0.55 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.37 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.87 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** 0.562 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.911 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0063 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.715 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -0.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 17.27 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** PFS Rate at 6 months **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0593 **P-Value Comment:** **Parameter Type:** Difference in Event Free Rate **Parameter Value:** 8.47 **Statistical Comment:** **Statistical Method:** Z-test **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.02 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** PFS Rate at 1 year **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0133 **P-Value Comment:** **Parameter Type:** Difference in Event Free Rate **Parameter Value:** 7.27 **Statistical Comment:** **Statistical Method:** Z-test **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 3.29 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 23.64 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** OS Rate at 1 year **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0095 **P-Value Comment:** **Parameter Type:** Difference in Event Free Rate **Parameter Value:** 13.46 **Statistical Comment:** **Statistical Method:** Z-test **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** 0.795 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.874 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Cough **Non-Inferiority Comment:** Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1). **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.3604 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 1.221 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.722 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.553 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Pain in Chest **Non-Inferiority Comment:** Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1). **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.7712 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 1.058 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.747 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.552 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Pain in Arm or Shoulder **Non-Inferiority Comment:** Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1). **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.6922 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 1.077 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.549 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.019 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Dyspnea **Non-Inferiority Comment:** Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1). **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0650 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.748 **Statistical Comment:** **Statistical Method:** Log Rank **Tested Non-Inferiority:** ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.2 - **Spread:** 4.2 - **Upper Limit:** 4.5 - **Value:** 4.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.4 - **Spread:** 4.4 - **Upper Limit:** 5.6 - **Value:** 5.2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9.3 - **Spread:** 9.3 - **Upper Limit:** 11.3 - **Value:** 10.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 10.8 - **Spread:** 10.8 - **Upper Limit:** 15.9 - **Value:** 12.3 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 70.29 - **Spread:** - **Upper Limit:** 82.38 - **Value:** 76.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 67.50 - **Spread:** - **Upper Limit:** 80.03 - **Value:** 74.1 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.9 - **Spread:** - **Upper Limit:** 3.9 - **Value:** 3.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3.5 - **Spread:** - **Upper Limit:** 4.2 - **Value:** 4.1 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16.56 - **Spread:** - **Upper Limit:** 28.22 - **Value:** 22.39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 24.26 - **Spread:** - **Upper Limit:** 37.45 - **Value:** 30.86 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.14 - **Spread:** - **Upper Limit:** 8.56 - **Value:** 5.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.85 - **Spread:** - **Upper Limit:** 17.40 - **Value:** 12.62 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38.23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.69 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** Insufficient number of participants with events. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** NA - **Comment:** Insufficient number of participants with events. - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** NA **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** Insufficient number of participants with events. - **Group ID:** OG000 - **Lower Limit:** 16.6 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Insufficient number of participants with events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** 20.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** Insufficient number of participants with events. - **Group ID:** OG000 - **Lower Limit:** 10.9 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Insufficient number of participants with events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** **Class:** ##### Category **Measurements:** - **Comment:** Insufficient number of participants with events. - **Group ID:** OG000 - **Lower Limit:** 8.8 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Insufficient number of participants with events. - **Group ID:** OG001 - **Lower Limit:** 9.2 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.6 - **Spread:** - **Upper Limit:** 8.8 - **Value:** 5.6 - **Comment:** Insufficient number of participants with events. - **Group ID:** OG001 - **Lower Limit:** 5.5 - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 96.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 100.0 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 196 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 188 **Units:** Participants #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 135 - **Upper Limit:** - **Value:** 389 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** Below the level of detection. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 194 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 32.1 - **Upper Limit:** - **Value:** 80.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 174 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 56.4 - **Upper Limit:** - **Value:** 138 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 156 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 73.5 - **Upper Limit:** - **Value:** 186 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 88 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 63.1 - **Upper Limit:** - **Value:** 196 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 22 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 43.4 - **Upper Limit:** - **Value:** 221 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 **Units:** Participants #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** Below level of detection. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA - **Comment:** Below level of detection. - **Group ID:** OG001 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 12 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4880 - **Upper Limit:** - **Value:** 13300 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5060 - **Upper Limit:** - **Value:** 11200 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 12 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1880 - **Upper Limit:** - **Value:** 7200 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1670 - **Upper Limit:** - **Value:** 6860 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 11 - **Group ID:** OG001 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 58.3 - **Upper Limit:** - **Value:** 144 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 48.1 - **Upper Limit:** - **Value:** 126 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 12 - **Group ID:** OG001 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3590 - **Upper Limit:** - **Value:** 13900 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5090 - **Upper Limit:** - **Value:** 11300 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 13 - **Group ID:** OG001 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1630 - **Upper Limit:** - **Value:** 7180 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2200 - **Upper Limit:** - **Value:** 6540 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 13 - **Group ID:** OG001 - **Value:** 13 **Units:** Participants #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** Below level of detection. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA - **Comment:** Below level of detection. - **Group ID:** OG001 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 12 - **Group ID:** OG001 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3640 - **Upper Limit:** - **Value:** 17000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2860 - **Upper Limit:** - **Value:** 19400 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 10 - **Group ID:** OG001 - **Value:** 10 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2010 - **Upper Limit:** - **Value:** 11100 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1960 - **Upper Limit:** - **Value:** 12600 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 8 - **Group ID:** OG001 - **Value:** 12 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2360 - **Upper Limit:** - **Value:** 7640 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1230 - **Upper Limit:** - **Value:** 7300 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 9 - **Group ID:** OG001 - **Value:** 9 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** Below level of detection. - **Group ID:** OG000 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA - **Comment:** Below level of detection. - **Group ID:** OG001 - **Lower Limit:** - **Spread:** NA - **Upper Limit:** - **Value:** NA **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 13 - **Group ID:** OG001 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2180 - **Upper Limit:** - **Value:** 16600 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3600 - **Upper Limit:** - **Value:** 17700 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 11 - **Group ID:** OG001 - **Value:** 9 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3740 - **Upper Limit:** - **Value:** 12400 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2810 - **Upper Limit:** - **Value:** 12200 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 10 - **Group ID:** OG001 - **Value:** 13 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1230 - **Upper Limit:** - **Value:** 6740 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2090 - **Upper Limit:** - **Value:** 7960 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 10 - **Group ID:** OG001 - **Value:** 11 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** Baseline until PD or death, whichever occurs first (up to approximately 23 months) **Title:** Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population **Type:** PRIMARY **Unit of Measure:** Months ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 2 **Description:** OS is defined as the time from randomization to death from any cause. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** Baseline until death from any cause (up to approximately 23 months) **Title:** Duration of Overall Survival (OS) in the Global Population **Type:** PRIMARY **Unit of Measure:** Months ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 3 **Description:** Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months) **Title:** Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 4 **Description:** DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months) **Title:** Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 5 **Description:** PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** 6 months, 1 year **Title:** PFS Rate at 6 Months and at 1 Year in Global Population **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 6 **Description:** OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively. **Parameter Type:** NUMBER **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** 1 year, 2 years **Title:** OS Rate at 1 Year and 2 Years in the Global Population **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 7 **Description:** TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment. **Reporting Status:** POSTED **Time Frame:** Baseline until deterioration per symptom subscale (up to approximately 23 months) **Title:** Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population **Type:** SECONDARY **Unit of Measure:** Month ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 8 **Description:** The percentage of participants with at least one adverse event in the global population. **Parameter Type:** NUMBER **Population Description:** The safety population included all treated participants, defined as participants who received any amount of any component of study treatment. For the safety analyses, patrticipants who received any amount of atezolizumab were analyzed as part of the Atezo + CE arm, even if atezolizumab was given in error. **Reporting Status:** POSTED **Time Frame:** Baseline until up to 90 days after end of treatment (up to approximately 49 months) **Title:** Percentage of Participants With at Least One Adverse Event in the Global Population **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 9 **Description:** The baseline prevalence and post-baseline incidence of ADAs against atezolizumab. **Parameter Type:** NUMBER **Population Description:** ADA analyses were based on ADA observations from participants who had received atezolizumab treatment and were evaluated for immunogenicity. **Reporting Status:** POSTED **Time Frame:** Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall) **Title:** Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 10 **Description:** Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample. **Reporting Status:** POSTED **Time Frame:** Post-dose Day 1 of Cycle 1 (cycle length = 21 days) **Title:** Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population **Type:** SECONDARY **Unit of Measure:** μg/mL ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 11 **Description:** Atezolizumab pre-dose plasma concentration (Cmin) for each respective day. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample. **Reporting Status:** POSTED **Time Frame:** Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days) **Title:** Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population **Type:** SECONDARY **Unit of Measure:** μg/mL ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 12 **Description:** Plasma concentration of carboplatin in the Global population. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample. **Reporting Status:** POSTED **Time Frame:** Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days) **Title:** Plasma Concentration of Carboplatin in the Global Population **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide #### Outcome Measure 13 **Description:** Plasma concentration of etoposide in the Global Population. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample. **Reporting Status:** POSTED **Time Frame:** Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days) **Title:** Plasma Concentration of Etoposide in the Global Population **Type:** SECONDARY **Unit of Measure:** ng/mL ##### Group **Description:** Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG000 **Title:** Placebo + Carboplatin + Etoposide ##### Group **Description:** Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** OG001 **Title:** Atezolizumab + Carboplatin + Etoposide ### Participant Flow Module #### Group **Description:** Participants in the Global population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** FG000 **Title:** Placebo + Carboplatin + Etoposide - Global #### Group **Description:** Participants in the Global population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** FG001 **Title:** Atezolizumab + Carboplatin + Etoposide - Global #### Group **Description:** Participants in the China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** FG002 **Title:** Placebo + Carboplatin + Etoposide - China #### Group **Description:** Participants in the China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor. **ID:** FG003 **Title:** Atezolizumab + Carboplatin + Etoposide - China #### Period **Title:** Global Period ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 167 ###### Reason **Group ID:** FG001 **Number of Subjects:** 151 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Study Terminated By Sponsor ###### Reason **Group ID:** FG000 **Number of Subjects:** 21 ###### Reason **Group ID:** FG001 **Number of Subjects:** 26 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 12 ###### Reason **Group ID:** FG001 **Number of Subjects:** 18 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 202 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 201 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 202 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 201 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 #### Period **Title:** China Period ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 46 ###### Reason **Group ID:** FG003 **Number of Subjects:** 48 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ##### Withdraw **Type:** Study Terminated By Sponsor ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ###### Reason **Group ID:** FG003 **Number of Subjects:** 4 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ###### Reason **Group ID:** FG003 **Number of Subjects:** 3 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 53 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 57 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 53 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 57 **Pre-Assignment Details:** The total study population included 503 participants. The Global population included 403 participants. An additional 100 participants enrolled during the China Extension. The total China population included 10 Chinese participants from the Global population plus 100 participants from the China extension. 10 participants were part of the Global as well as China populations. Separate analyses were performed for the Global population and the China population in the study. **Recruitment Details:** Participants were enrolled at 114 centers in 21 countries: United States of America, Poland, Japan, Russia, Spain, Austria, Hungary, Czech Republic, South Korea, Italy, Serbia, Australia, Greece, United Kingdom, Germany, Taiwan, France, Chile, Brazil, Mexico, and China. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02100579 **Brief Title:** Ultrasound-guided Adductor Canal Block for Total Knee Replacement **Official Title:** Ultrasound-guided Adductor Canal Block for Total Knee Replacement: a Randomized, Double-blind Placebo Controlled Trial. #### Organization Study ID Info **ID:** STU00088239 #### Organization **Class:** OTHER **Full Name:** Northwestern University #### Secondary ID Infos **Domain:** Northwestern University IRB **ID:** STU00088239 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-07-11 **Type:** ACTUAL **Last Update Submit Date:** 2017-06-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-10 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-11-02 **Type:** ESTIMATED **Results First Submit Date:** 2016-09-14 **Results First Submit QC Date:** 2016-09-14 #### Start Date **Date:** 2014-03 **Status Verified Date:** 2017-06 #### Study First Post Date **Date:** 2014-04-01 **Type:** ESTIMATED **Study First Submit Date:** 2014-03-25 **Study First Submit QC Date:** 2014-03-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Northwestern University #### Responsible Party **Investigator Affiliation:** Northwestern University **Investigator Full Name:** Antoun Nader **Investigator Title:** Professor of Anesthesiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Total knee arthroplasty is associated with intense early postoperative pain. Fast track recovery programs including early therapy protocols and early hospital discharge are being implemented at various hospitals. The postoperative analgesic pain regimen should enhance functional recovery in addition to providing efficient analgesia with minimal side effects. Adductor canal blockade is commonly used to provide postoperative analgesia for total knee arthroplasty (TKA) surgery. The investigators hypothesize that an ultrasound guided adductor canal block will lower narcotic consumption and improved overall satisfaction compared to ultrasound guided sham block with normal saline (placebo) for patients undergoing minimally invasive TKA surgery. **Detailed Description:** The investigators hypothesize that an ultrasound guided adductor canal block will lower narcotic consumption and improved overall satisfaction compared to ultrasound guided sham block with normal saline (placebo) for patients undergoing minimally invasive TKA surgery. ### Conditions Module **Conditions:** - Complications; Arthroplasty - Knee Injuries ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine **Intervention Names:** - Drug: Bupivacaine **Label:** Active Group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline **Intervention Names:** - Drug: Preservative free normal saline **Label:** Control Group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Active Group **Description:** 10 ml of 0.25% bupivacaine **Name:** Bupivacaine **Other Names:** - Sensorcaine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Control Group **Description:** 10 ml of preservative free normal saline **Name:** Preservative free normal saline **Other Names:** - 0.9% sodium chloride **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Opioid consumption (morphine equivalents) **Measure:** Opioid Consumption (mg morEq) **Time Frame:** 36 hours #### Secondary Outcomes **Description:** Visual Analog Scale pain score; 0 = no pain, 10 = excruciating pain) in the knee recorded every 6 hours up to 36hrs following surgery. **Measure:** Visual Analog Scale Pain Score **Time Frame:** Pain burden at 36hr **Description:** The average time to discharge in hours. Participants were discharged home went physical therapy criteria were met. **Measure:** Length of Hospitalization **Time Frame:** 0 to 192 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participants 40 to 75 years old who are presenting for minimally invasive total knee arthroplasty under spinal anesthesia Exclusion Criteria: * Patient refusal * American Society of Anesthesiologists physical status classification of 4 or higher * Pre-existing neuropathy in the femoral or sciatic distribution * Coagulopathy * Infection at the site * Chronic opioid use (greater than 3 months) * Pregnancy * Medical conditions limiting physical therapy participation * Any other contra-indication to regional anesthesia **Maximum Age:** 75 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chicago **Country:** United States **Facility:** Northwestern University Feinberg School of Medicine **State:** Illinois **Zip:** 60611 #### Overall Officials **Official 1:** **Affiliation:** Northwestern University Feinberg School of Medicine **Name:** Antoun Nader, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007869 - Term: Leg Injuries - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10738 - Name: Knee Injuries - Relevance: HIGH - As Found: Knee Injuries - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007718 - Term: Knee Injuries ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002045 - Term: Bupivacaine ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Active Group **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine Bupivacaine: 10 ml of 0.25% bupivacaine **ID:** EG000 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Active Group **Group ID:** EG001 **Title:** Control Group **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline Preservative free normal saline: 10 ml of preservative free normal saline **ID:** EG001 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Control Group **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 20 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 40 **Units:** Participants ### Group **ID:** BG000 **Title:** Active Group **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine Bupivacaine: 10 ml of 0.25% bupivacaine ### Group **ID:** BG001 **Title:** Control Group **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline Preservative free normal saline: 10 ml of preservative free normal saline ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 9 #### Measurement **Group ID:** BG002 **Value:** 17 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 23 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 62 **Upper Limit:** 73 **Value:** 68 #### Measurement **Group ID:** BG001 **Lower Limit:** 59 **Upper Limit:** 72 **Value:** 67 #### Measurement **Group ID:** BG002 **Lower Limit:** 62 **Upper Limit:** 72 **Value:** 67 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 13 #### Measurement **Group ID:** BG002 **Value:** 28 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 12 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** a-nader2@northwestern.edu **Organization:** Northwestern University, Feinberg School of Medicine **Phone:** 312-695-3045 **Title:** Antoun Nader ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 39 - **Spread:** - **Upper Limit:** 61 - **Value:** 48 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 49 - **Spread:** - **Upper Limit:** 85 - **Value:** 60 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 37 - **Spread:** - **Upper Limit:** 120 - **Value:** 71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 92 - **Spread:** - **Upper Limit:** 161 - **Value:** 131 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 64 - **Spread:** - **Upper Limit:** 83 - **Value:** 73 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 76 - **Spread:** - **Upper Limit:** 111 - **Value:** 92 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Opioid consumption (morphine equivalents) **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** 36 hours **Title:** Opioid Consumption (mg morEq) **Type:** PRIMARY **Unit of Measure:** Morphine Equivalents ##### Group **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine Bupivacaine: 10 ml of 0.25% bupivacaine **ID:** OG000 **Title:** Active Group ##### Group **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline Preservative free normal saline: 10 ml of preservative free normal saline **ID:** OG001 **Title:** Control Group #### Outcome Measure 2 **Description:** Visual Analog Scale pain score; 0 = no pain, 10 = excruciating pain) in the knee recorded every 6 hours up to 36hrs following surgery. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Pain burden at 36hr **Title:** Visual Analog Scale Pain Score **Type:** SECONDARY **Unit of Measure:** scores*hours ##### Group **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine Bupivacaine: 10 ml of 0.25% bupivacaine **ID:** OG000 **Title:** Active Group ##### Group **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline Preservative free normal saline: 10 ml of preservative free normal saline **ID:** OG001 **Title:** Control Group #### Outcome Measure 3 **Description:** The average time to discharge in hours. Participants were discharged home went physical therapy criteria were met. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 0 to 192 hours **Title:** Length of Hospitalization **Type:** SECONDARY **Unit of Measure:** hours ##### Group **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine Bupivacaine: 10 ml of 0.25% bupivacaine **ID:** OG000 **Title:** Active Group ##### Group **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline Preservative free normal saline: 10 ml of preservative free normal saline **ID:** OG001 **Title:** Control Group ### Participant Flow Module #### Group **Description:** Ultrasound-guided adductor canal blockade with 10 ml of 0.25% bupivacaine Bupivacaine: 10 ml of 0.25% bupivacaine **ID:** FG000 **Title:** Active Group #### Group **Description:** Ultrasound-guided sham block with 10 ml of preservative free normal saline Preservative free normal saline: 10 ml of preservative free normal saline **ID:** FG001 **Title:** Control Group #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02294279 **Acronym:** NSRS **Brief Title:** The Evaluation of FeNO for Predicting Response to ICS in Subjects With Non-specific Respiratory Symptoms **Official Title:** The Evaluation of FeNO for Predicting Response to an Inhaled Corticosteroid in Subjects With Non-specific Respiratory Symptoms #### Organization Study ID Info **ID:** OR01013 #### Organization **Class:** NETWORK **Full Name:** Research in Real-Life Ltd ### Status Module #### Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-04-25 **Type:** ACTUAL **Last Update Submit Date:** 2017-04-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Start Date **Date:** 2014-05 **Type:** ACTUAL **Status Verified Date:** 2017-04 #### Study First Post Date **Date:** 2014-11-19 **Type:** ESTIMATED **Study First Submit Date:** 2014-11-14 **Study First Submit QC Date:** 2014-11-18 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Aerocrine AB #### Lead Sponsor **Class:** NETWORK **Name:** Research in Real-Life Ltd #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Nitric Oxide is recognized as a biological marker for many chronic airway diseases. It has been standardised for clinical use indicating airway inflammation. In clinical practice, FeNO can aid confirmation of an asthma diagnosis and can indicate the degree of steroid-responsiveness. This can help guide physician decisions on the initiation of inhaled corticosteroid (ICS) therapy, or adjustment of ICS therapy. Therefore, FeNO measurement could be particularly useful to confirm an asthma diagnosis in patients with non-specific respiratory symptoms (≥ 6 weeks of cough and/or wheezing and/or chronic dyspnoea) and to assess how likely they are to benefit from corticosteroid treatment. This study will assess the suitability of FeNO to predict ICS responsiveness in patients with non-specific respiratory symptoms. Additionally, we would like to determine the suitability of FeNO as a diagnostic tool for asthma in comparison to conventional predictors, e.g. spirometry. **Detailed Description:** Randomised, double-blind, placebo-controlled trial with planned enrolment of 264 patients from the UK and Singapore. Eligible patients are 18-80 years old with ≥6 weeks' duration of non-specific respiratory symptoms defined as cough and/or wheeze and/or dyspnoea. Patients with FEV1 \<90% predicted at visit 1 must show reversibility of \<20% at visit 1 or within the prior year. Key exclusion criteria are prior diagnosis of asthma; evidence of concomitant chronic respiratory disease, respiratory tract infection; or known significant risk factor for cough or wheeze. Baseline assessments will include spirometry (FEV1, forced vital capacity) and FeNO measurement. Patients will be provided with a peak flow meter for twice daily measurement throughout the study. At 2 weeks, a clinical assessment and spirometry will be performed to confirm eligibility, and patients will complete four validated questionnaires to assess quality of life, asthma control, and asthma symptoms, including a visual analog scale for bother from asthma symptoms. Eligible patients will then be stratified by baseline FeNO level (normal ≤25, intermediate \>25 to ≤50, or high \>50 ppb); each group will be randomised to receive beclometasone 400 mcg daily or placebo for 6 weeks. An optional blood sample will be collected from consenting patients to assess blood eosinophils. At visit 3, final assessments will include spirometry, FeNO measurement, and all questionnaires. Interaction analysis will be used to determine whether a differential effect exists in response to ICS between FeNO groups. ### Conditions Module **Conditions:** - Asthma **Keywords:** - cough, wheeze, dyspnoea ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 360 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 4 weeks of corticosteroid treatment with QVAR (100mcg), 400 mcg daily; two puffs twice daily **Intervention Names:** - Drug: Qvar (100 mcg) **Label:** Active **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Blinded placebo inhaler **Label:** Placebo **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Active **Description:** 2 puffs twice daily; 400 mcg daily over 4 weeks treatment period **Name:** Qvar (100 mcg) **Other Names:** - Beclomethasone diproprionate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The Asthma control questionnaire (ACQ) is a seven question (i.e. the top scoring 5 symptoms, daily rescue bronchodilator use and FEV1% pred.), validated tool for assessing asthma control. Patients are asked to recall how their asthma has been during the last 7 days and to evaluate their asthma against 5 symptom questions and a rescue bronchodilator use question on a 6-point scale (0 = no impairment, 6 = maximum impairment). In addition, the research nurse will grade the FEV1 % predicted on a 6 point scale (0 to 6). The questions are equally weighted and ACQ7 score is the mean of the 7 questions, generating a value between 0 (totally controlled) and 6 (severely uncontrolled). **Measure:** Asthma Control Questionnaire (ACQ) **Time Frame:** Baseline and 4 weeks #### Secondary Outcomes **Description:** The EQ-5D-3L questionnaire is a validated instrument that derives a person's health profile. The EQ-5D-3L consists of two parts. The first one is the EQ descriptive system which comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The respondent is asked to indicate their health state by ticking the most appropriate statement (no problems to extreme problems). The second part is the EQ visual analog scale (EQ VAS). It records the respondent's self-rated health on a 20 cm vertical,visual analogue scale with endpoints labelled "the best health you can imagine" and "the worst health you can imagine". **Measure:** EuroQol 5 dimension questionnaire **Time Frame:** Baseline and 4 weeks **Description:** Patients rate their symptom/cough severity by placing a mark on a line to indicate symptom severity. **Measure:** Visual Analogue Scale test (VAS) and cough Visual analogue scale test **Time Frame:** Baseline and 4 weeks **Description:** Spirometry will be conducted to obtain an objective measure of the patient's lung function **Measure:** Spirometry (PEF, FEV1, FVC, FEV1/FVC) **Time Frame:** 3 days **Description:** A blood test will be taken from consenting patients to assess the eosinophil level as marker for inflammation. **Measure:** Eosinophil analysis **Time Frame:** 1 day **Description:** Peak expiratory flow will be measured using a portable peak flow meter. **Measure:** Peak expiratory flow (PEF diary) **Time Frame:** From visit 1 till 6 weeks follow-up (2 recordings per day over 6 weeks) **Description:** Clinical judgment on whether the treatment was successful on a 5-point scale **Measure:** Global Evaluation of Treatment Effectiveness Scale (GETE) **Time Frame:** 1 day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Written informed consent is obtained before conducting any study-related procedures * The patient is a man or woman aged 18 to 80 years as of the screening visit * The patient is experiencing non-specific respiratory symptoms defined as follows: Cough and/or wheeze and/or chronic dyspnoea for ≥ 6 weeks prior to visit 1 * Patients displaying an FEV1\< 90% predicted at visit 1, will also need to show a reversibility to a short-acting beta-agonist of \< 20% at visit 1 or within the previous year * Women of childbearing potential (post-menarche or less than 2 years post-menopausal or not surgically sterile) must be willing to commit to using a medically accepted method of contraception for the duration of the study. Accepted methods of contraception include: intrauterine devices (IUD), systemic contraception e.g. steroidal contraceptives (oral, implanted transdermal or injected), barrier methods with spermicide, and partner vasectomy Exclusion Criteria: * The patient has ever been diagnosed with asthma as evidenced by the UK quality outcome framework approved Read code as well as a reversibility of ≥ 20% predicted * The patient has received oral, inhaled or systemic corticosteroids, a leukotriene modifier or long-acting-beta-agonist within four weeks prior to visit 1. All therapy and treatment other than those outlined are permitted during the study * The patient has a significant chronic respiratory disorder other than asthma, e.g. COPD (fixed obstruction, post-bronchodilator) cystic fibrosis, severe and untreated bronchiectasis or interstitial lung disease * The patient has a significant medical condition that would make it unlikely for the patient to complete the study * The patient has a known significant risk factor for cough or wheeze, including but not limited to: taking an ACE inhibitor, severe untreated rhinitis, or significant gastroesophageal reflux disease * The patient is asymptomatic (ACQ \< 1) after the initial 2-week assessment * The patient has had a respiratory tract infection as judged clinically, within four weeks prior to visit 1, or displays an acute respiratory tract infection at the time of the study * The patient is a pregnant woman or intends to get pregnant (Any woman becoming pregnant during the study will be withdrawn from the study) **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Oakington **Country:** United Kingdom **Facility:** Research in Real Life Ltd **State:** Cambridgeshire **Zip:** CB24 3BA #### Overall Officials **Official 1:** **Affiliation:** Research in Real Life **Name:** David Price, Prof **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** Principal investigator has not made a decision regarding a plan to share data at this point in time. **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Price DB, Buhl R, Chan A, Freeman D, Gardener E, Godley C, Gruffydd-Jones K, McGarvey L, Ohta K, Ryan D, Syk J, Tan NC, Tan T, Thomas M, Yang S, Konduru PR, Ngantcha M, d'Alcontres MS, Lapperre TS. Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial. Lancet Respir Med. 2018 Jan;6(1):29-39. doi: 10.1016/S2213-2600(17)30424-1. Epub 2017 Nov 3. **PMID:** 29108938 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M4556 - Name: Asthma - Relevance: LOW - As Found: Unknown - ID: M27137 - Name: Respiratory Aspiration - Relevance: LOW - As Found: Unknown - ID: M7591 - Name: Dyspnea - Relevance: LOW - As Found: Unknown - ID: M6590 - Name: Cough - Relevance: LOW - As Found: Unknown - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: HIGH - As Found: Respiratory Symptoms ### Condition Browse Module - Meshes - ID: D000012818 - Term: Signs and Symptoms, Respiratory ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4800 - Name: Beclomethasone - Relevance: HIGH - As Found: Bronchoscopy - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000001507 - Term: Beclomethasone ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04761679 **Brief Title:** Nasal Bridge Pressure Injury Prevention **Official Title:** Nasal Bridge Pressure Injury Prevention Using Protective Dressing and Halyard Fluidshield N95 Mask #### Organization Study ID Info **ID:** AAAT2889 #### Organization **Class:** OTHER **Full Name:** Columbia University ### Status Module #### Completion Date **Date:** 2022-01-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-05-19 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-13 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2022-01-04 **Type:** ACTUAL #### Start Date **Date:** 2021-03-23 **Type:** ACTUAL **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2021-02-21 **Type:** ACTUAL **Study First Submit Date:** 2021-02-16 **Study First Submit QC Date:** 2021-02-16 **Why Stopped:** Evolution of the COVID19 pandemic with subsequent spread to all areas of clinical care severely affected the number of potential participants that were able to safely participate in the study. ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Columbia University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary goal of this study is to explore whether applying the Mepilex foam on the nasal bridge directly between the skin and the N95 mask will prevent nasal bridge pressure injury among nursing staff, secondary to long-term ( \>8+ hours) wear time. The secondary goal is to evaluate if using the Mepilex maintains the seal of the mask. **Detailed Description:** Nurses use the N95 Mask as part of the personal protective equipment (PPE) when caring for patients with COVID-19. The N95 mask covers their nose and mouth with a tight seal. Nurses wear the mask for more than 8 hours per day, as a result they are at increased risk for skin injury on the nasal bridge. Mepliex is foam dressing which has been used to prevent pressure injuries to the skin. This study will evaluate if using Mepilex or band-aid on the nasal bridge of the nurses who wear the N95 for more than 8 hours decreases the potential for skin injury. In addition, the investigators will test if the Mepilex or band-aid also maintains the seal of the mask. Maintaining the seal is important to ensure that the nurse is not exposed to the virus. The investigators will be working with nurses who do not directly take care of COVID-19 patients to ensure the safety of all participants. ### Conditions Module **Conditions:** - Pressure Ulcer of Skin - Pressure Injury **Keywords:** - Pressure Injury Prevention - Personal Protective Equipment - Nursing - Nasal Bridge - N-95 Mask ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Masking Description:** Single-blind design **Who Masked:** - PARTICIPANT **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: Applying the Mepilex foam **Label:** Intervention Group **Type:** EXPERIMENTAL #### Arm Group 2 **Label:** Control Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention Group **Description:** Mepilex foam will be directly applied on the nasal bridge directly between the skin and the N95 mask. **Name:** Applying the Mepilex foam **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Researchers will count the number of participants with and without injury on the nasal bridge directly between the skin and the N95 mask **Measure:** Number of Participants with Pressure Injury Prevention **Time Frame:** 48 hours #### Secondary Outcomes **Description:** Researchers will assess the integrity of the N95 mask seal using both interventions - Mepilex and Band-Aid. The number of participants with acceptable seal according to the Fit Test will be counted **Measure:** Number of Participants that Maintain Mask Seal Integrity **Time Frame:** 12 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * The sample will consist of nursing staff working on non-COVID units, including: Medical Surgical Units, Operating Rooms or Ambulatory Care- Labor and Delivery Unit, Maternity Unit and Medical Oncology Unit, at NewYork-Presbyterian (NYP) Lawrence Hospital. Exclusion Criteria: * Exclusion Criteria: A score on \> 5 the COVID Anxiety Scale. The scale has 4 questions with 5 possible options (rated 1 - 5), to evaluate the effect of COVID19 on the individual. The lowest possible score is 0, the highest possible score is 20. A score of 5 states that the individual experiences COVID19 related anxiety for 'Rarely' or 'Not at All". Excluding participants with a score of \> 5 will prevent unnecessary harm to study participants or exacerbate symptoms of anxiety. * Nurses working in the Emergency Department, Intensive Care Unit or a unit with a focus on the exposed COVID-19 population * Non-clinical nurses, volunteer or agency registered nurses * Known history of skin breakdown or damage to the nasal bridge * History of skin-related conditions including (acne vulgaris, Psoriasis, Herpetic lesions to mouth, nasal areas) * History of surgery to nasal bridge * Pregnant nurses in their third trimester * History of respiratory extended respirator use in addition to the hours collected in this study. **Maximum Age:** 64 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New York **Country:** United States **Facility:** Columbia University Irving Medical Center/NYP **State:** New York **Zip:** 10032 #### Overall Officials **Official 1:** **Affiliation:** Columbia University **Name:** Hazel Holder, MSN, RN, ACCNS-AG, CCRN **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Coded participant data will be made available to future researchers with a goal to replicate this study and add to the body of nursing knowledge **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012883 - Term: Skin Ulcer - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M6870 - Name: Pressure Ulcer - Relevance: HIGH - As Found: Pressure Injury - ID: M17206 - Name: Ulcer - Relevance: LOW - As Found: Unknown - ID: M834 - Name: Crush Injuries - Relevance: HIGH - As Found: Pressure Injury - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M15686 - Name: Skin Ulcer - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003668 - Term: Pressure Ulcer - ID: D000014947 - Term: Wounds and Injuries - ID: D000071576 - Term: Crush Injuries ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03487679 **Brief Title:** Effects of Prolonged Fasting on Microbiome and HDL **Official Title:** The Effects of Prolonged Fasting on the Microbiome and HDL Particles of Human Subjects #### Organization Study ID Info **ID:** 918915 #### Organization **Class:** OTHER **Full Name:** University of California, Davis ### Status Module #### Completion Date **Date:** 2018-05-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-09-27 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-05-30 **Type:** ACTUAL #### Start Date **Date:** 2018-04-09 **Type:** ACTUAL **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2018-04-04 **Type:** ACTUAL **Study First Submit Date:** 2018-03-01 **Study First Submit QC Date:** 2018-03-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of California, Davis #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Participants will undergo one day of habitual eating followed by 36 hours of water only fasting and final day of habitual eating of the exact same diet consumed on the first eating day. Blood draws will be performed on Day 1 in a 10-12 hr fasted state and 2 hour postprandial state and again on Day 3 in a 36hr fasted state and a 2 hour post prandial state. Microbiome samples and blood glucose data will be collected throughout the course of the study. **Detailed Description:** Screening and Consent: Prospective subjects who pass the initial phone screening interview (i.e. meet inclusion/exclusion criteria) will be admitted into the study and scheduled for a consent visit. At the consent visit, subjects who decide to participate will be given a series of questionnaires including a health history questionnaire, physical activity questionnaire, and will be asked to complete a 3-day diet record, to be completed before the baseline visit at the beginning of the study. Women who consent to participate will be scheduled to complete the study within the follicular phase and menses of the menstrual cycle to avoid confounding alterations in lipoproteins. Study Visit1 (Baseline fasted): On Day 1 of the study protocolstudy participants will report to the Ragle Human Nutrition Research Center located on the UC Davis campus (1283 Academic Surge, University of California, Davis, in Davis CA 95616) for a 12-hour overnight fasting blood draw and anthropometric measurements at approximately 8AM. Any participants that are found to have fasting glucose above or below 70-100mg/dL will be removed from the study. Study participants will be given a Precision Xtra Blood Ketone Testing Kit to collect blood ketone data during the fasting period of the study protocol, a set of stool collection kits to collect stool samples throughout the rest of the study protocoland fitted with a GoBe activity monitor to track physical activity throughout the rest of the study protocol. Proper use, care, and storage of the Precision Xtra systems, stool collection kits, and GoBe monitors will be explained in detail to study participants during the baseline visit. Study participants will be given a 24-hr food diary to record their food and beverage intake throughout the rest of the day or may be asked to track their diet using GB 360. Study Visit 2 (Baseline postprandial): After the baseline visit on Day 1 of the study protocol, study participants will go about their normal routines and eat their habitual diet ad libitum while recording their dietary intake throughout the day. This food record will be used in order for the study participants to mimic their food intake on Day 1 during the eating period on Day 3 of the study protocol. Study participants will eat their last meal of the day at approximately 6PM. Post-prandial blood samples will be collected at 2 hours after the ingestion of this last meal and immediately processed to yield patient plasma and isolated PBMCs to be stored for future analysis. These post-prandial samples will constitute the baseline "Fed" state of each participant. Study participants will also perform their first bloodprick for ketone measurement using the Precision Xtra Monitor under instruction and supervision by study personnel. Fasting: After ingestion of their final meal, participants will undergo a full 36 hours of fasting comprising Day 2 and the beginning of Day 3 of the trial without otherwise modifying their typical routine, including drinking coffee or tea (but with no creamers or sweeteners of any kind), if this is part of their normal routine. The time of the ingestion of the standardized meal will be used as the start point (0hr) for the continuous 36 hours of fasting. 36 hrs of fasting has been shown to be well tolerated in human subjects and was chosen for this trial as it represents the approximate amount of time that fasting would be experienced during a single cycle of an alternate day fasting regimen. Therefore, results from this study could be generalized to plan for future studies of alternate day fasting. Subjects will be encouraged to report any feelings of dizziness, headaches, nausea, or severe hunger that they may experience and, based on the severity of their conditions, will be advised whether or not to continue with the trial. Subjects will be asked to take small blood pricks starting immediately after waking up on Day 2 and then every 3 conscious hours thereafter using thePrecision Xtra Blood Ketone Testing Kits in order to test blood ketone levels during the fasting period. Ketone levels obtained from the blood pricks will be recorded automatically by the Precision Xtra monitor. Study Visit 3 (Post 36h fasted): At 36 hours of fasting, roughly 8AM on Day 3, subjects will return to the Ragle Center, perform a final blood prick for ketone monitoring by the Precision Xtra and their blood samples will be collected and again immediately processed and stored for future analysis constituting the "Fasted" state for each participant. Study Visit 4 (Post 36h postprandial): After the blooddraw at Study Visit 3, study participants will be allowed free access to food throughout the rest of the day and asked to eat an identical diet to the dietary intake the participants recorded on Day 1 in their 24 hour food diary. Subjects will eat their last meal at approximately 6PM. Post-prandial blood samples will be collected at 2 hours after the ingestion of this last meal and immediately processed to yield patient plasma and isolated PBMCs to be stored for future analysis. These post-prandial samples will constitute the "Refed" state of each participant. After this final blood draw, the Precision Xtra system will be collected, the GoBe removed, and the activity and ketone data collected throughout the course of the study will be transferred to a secure computer for analysis. Fasting compliance will be determined as 1) increasing or steady ketone levels throughout the 36hr fasting period and 2) the absence of significant drops in blood ketone levels, which would indicate food intake and noncompliance. StoolCollection (Days 1-3): Study participants will use the provided stool collection kits to collect stool samples from each bowel movement throughout the entire course of the study. Stool samples will be obtained from study participants at the Ragle Center as soon as possible after initial collection by study participants, frozen, and stored at -80C. ### Conditions Module **Conditions:** - Fasting **Keywords:** - Microbiome - High Density Lipoprotein - Inflammation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 21 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will undergo one day of habitual eating followed by 36 hours of water only fasting and final day of habitual eating of the exact same diet consumed on the first eating day. Blood draws will be performed on Day 1 in a 10-12 hr fasted state and 2 hour postprandial state and again on Day 3 in a 36hr fasted state and a 2 hour post prandial state. Microbiome samples and blood glucose data will be collected throughout the course of the study. **Intervention Names:** - Other: Fasting **Label:** Fasting **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Fasting **Description:** Participants will undergo one day of habitual eating followed by 36 hours of water-only fasting and final day of habitual eating consuming the exact same diet consumed on the first eating day. Blood draws will be performed on Day 1 in a 10-12 hr fasted state and 2 hour postprandial state and again on Day 3 in a 36hr fasted state and a 2 hour post prandial state. Microbiome samples and blood glucose data will be collected throughout the course of the study. **Name:** Fasting **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** HDL will be isolated from plasma samples and HDL immunomodulatory capacity will be assessed in isolated HDL with an in vitro assay using stimulated macrophages. **Measure:** Change in HDL Immunomodulatory Capacity **Time Frame:** Baseline fasted vs. Post 36 hours fasted #### Secondary Outcomes **Description:** Gut microbial composition will be assessed by sequencing of isolated DNA from stool samples. **Measure:** Change in Gut Microbiome Composition **Time Frame:** Baseline fasted vs. Post 36 hours fasted ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - Age: 20-40 years old to constitute a young study population; 60-80 years old to constitute an elderly study population * BMI: 19-27 kg/m2 to constitute a normal/healthy weight population * Weight: 133lbs or more * Fasting Glucose: 70-100mg/dL to ensure that fasting can be tolerated without inducing dangerously low levels of blood glucose * Subjects must be willing to undergo a period of 36 hours of water-only fasting * Subjects must be willing to collect samples of each bowel movement produced throughout the entire study period for microbiome analysis. * Subjects must be willing to collect and test blood pricks for blood glucose levels using a Contour Next ONE Blood Glucose Kit during the fasting stage of the study protocol. * Subjects must be willing to continuously wear a GoBe activity monitor throughout the course of the trial. Exclusion Criteria: * Smoker * Anemia * Pregnancy or current breast-feeding * Documented chronic diseases including diabetes, thyroid disease, metabolic syndrome, cancer, or previous cardiovascular events * Any inflammatory bowel disease including IBS, Crohn's Disease, Celiac Disease * Consumption of \>1 alcoholic drink/day * Current consumption of any probiotic or prebiotic supplements * Extreme dietary or exercise patterns * Recent weight fluctuations (greater than 10% in the last six months) * Regular use of over-the-counter allergy or pain medications (\>1/week) * Taking prescription lipid medications (e.g. statins) or other supplements known to alter lipoprotein metabolism such as isoflavones. **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Davis **Country:** United States **Facility:** University of California Davis **State:** California **Zip:** 95616 #### Overall Officials **Official 1:** **Affiliation:** UC Davis **Name:** Angela M Zivkovic, Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04288479 **Acronym:** HITFLOW **Brief Title:** Acute Effects of High Intensity Training in Pregnancy on Fetal Well-being and Blood Flow Distribution **Official Title:** Acute Effects of HIT on Fetal Well-being and Blood Flow Distribution - a Pilot Study #### Organization Study ID Info **ID:** 62993 #### Organization **Class:** OTHER **Full Name:** Norwegian University of Science and Technology ### Status Module #### Completion Date **Date:** 2025-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-03 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-02 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-02-23 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2020-02-28 **Type:** ACTUAL **Study First Submit Date:** 2020-02-26 **Study First Submit QC Date:** 2020-02-26 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** St. Olavs Hospital #### Lead Sponsor **Class:** OTHER **Name:** Norwegian University of Science and Technology #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Pregnant women are recommended to be physically active ≥150 min/week, but \<15% of Norwegian women attain this goal. Several well-designed studies on lifestyle interventions focusing primarily on exercise training in overweight/obese pregnant women have reported disappointing outcomes with regard to maternal glycemic control, gestational weight gain and infant outcomes. Low adherence to the training program was found to be a problem; the participants did not enjoy the exercise program and had difficulties scheduling time to exercise. Pregnant women also report that they are not sure what exercises are safe during pregnancy. High intensity interval training (HIT), defined as short periods of intense activity separated by low-intensity breaks, has proved to induce superior improvements in insulin sensitivity and fitness compared with continuous moderate intensity training in individuals at increased risk for cardiometabolic diseases. Even short-term (6 weeks) HIT with brief (15-60 sec) work-bouts and a total time commitment of \<45 min per week, improves insulin sensitivity similar to that attained after 6 months of traditional endurance training. HIT is feasible and enjoyable for individuals with low fitness level and with obesity. HIT is therefore a highly potent intervention that elicits important changes in a range of clinically relevant health outcomes in reproductive-aged women. This study will investigate fetal responses to a single bout of HIT. Preliminary data of the investigators suggest that HIT does not negatively influence fetal heart rate. Others have reported that uterine and umbilical blood flow are not changed during or following acute exercise. However, no previous study has determined the acute effect of HIT on uterine blood flow and there are no studies investigating the fetal blood flow distribution in response to exercise. Since the relative distribution of blood to the fetal liver is associated with newborn adiposity, fetal blood flow distribution in response to exercise can provide insight about the effect of maternal exercise on offspring health. ### Conditions Module **Conditions:** - Pregnancy **Keywords:** - Exercise - High Intensity Interval Training - Pregnancy Outcome - Placental Circulation - Fetal Blood - Heart Rate, Fetal ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** before-after intervention effect measurement ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: Single high-intensity interval training session **Label:** Doing a single HIT session in gestational week 22-36 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Doing a single HIT session in gestational week 22-36 **Description:** 10 minutes warming up at low-to-moderate intensity, 8x30 seconds high intensity interval training with fetal heart rate measurement after each 30 second work-bout, 2 minutes recovery at low-to-moderate intensity. Continuous monitoring of maternal heart rate. **Name:** Single high-intensity interval training session **Other Names:** - HIT **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** examined by Doppler ultrasound during 30 minutes **Measure:** blood flow in fetal veins **Time Frame:** 1 day **Description:** examined by Doppler ultrasound during 30 minutes **Measure:** blood flow in fetal arteries **Time Frame:** 1 day #### Secondary Outcomes **Measure:** maternal heart rate **Time Frame:** 1 dag **Measure:** Fetal heart rate **Time Frame:** 1 day **Measure:** Umbilical vein diameter **Time Frame:** 1 day **Measure:** Maternal systolic blood pressure **Time Frame:** 1 day **Measure:** Maternal diastolic blood pressure **Time Frame:** 1 day **Measure:** Maternal body weight **Time Frame:** 1 day **Measure:** Maternal height **Time Frame:** 1 day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * pregnant, gestational week 22-36 * singleton fetus * no known diseases * capable of cycling on an ergometer bike Exclusion Criteria: * hypertension * gestational diabetes mellitus * any contraindication to exercise training **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** trine.moholdt@ntnu.no **Name:** Trine Moholdt, phd **Phone:** +47 73412007 **Role:** CONTACT **Contact 2:** **Email:** guro.rosvoldt@ntnu.no **Name:** Guro Rosvold **Role:** CONTACT #### Locations **Location 1:** **City:** Trondheim **Contacts:** ***Contact 1:*** - **Email:** trine.moholdt@ntnu.no - **Name:** Trine Moholdt, phd - **Role:** CONTACT **Country:** Norway **Facility:** Dept Circulation and Medical Imaging, EXCAR Exercise Lab **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** St Olavs Hospital, Dept of Obstetrics and Gynecology **Name:** Kjell Å Salvesen, md prof **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Norwegian University of Science and Technology **Name:** Trine Moholdt, phd **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: Rare - Name: Rare Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04436679 **Acronym:** CaPaLong **Brief Title:** INTER-Regional COHORTE of Long Term Pancreatic Cancer Survivors **Official Title:** INTER-Regional COHORTE of Long Term Pancreatic Cancer Survivors #### Organization Study ID Info **ID:** 2019_29 #### Organization **Class:** OTHER **Full Name:** University Hospital, Lille #### Secondary ID Infos **Domain:** ID-RCB number,ANSM **ID:** 2019-A02001-56 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2025-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-05-23 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-17 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-02 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-02 **Type:** ACTUAL **Status Verified Date:** 2022-04 #### Study First Post Date **Date:** 2020-06-18 **Type:** ACTUAL **Study First Submit Date:** 2020-06-15 **Study First Submit QC Date:** 2020-06-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Lille #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study is particularly innovative as it will accurately analyze the microscopic characteristics of the stroma, tumor budding and mucin expression in adenocarcinomas of the pancreas, using a comparative approach of long-survivor/short-survival patients. ### Conditions Module **Conditions:** - Pancreas Cancer - Pancreatic Adenocarcinoma **Keywords:** - survival - prognosis - tissue - pancreas cancer ### Design Module #### Bio Spec **Description:** tissues paraffin lumbered paraffin blocks of tissue-microarrays **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 144 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Tissue analysis will be performed by conventional microscopy and will evaluate histological markers known in the literature to have a prognostic impact. **Measure:** Relationship between known prognostic histological markers of pancreatic adenocarcinoma and patient survival. **Time Frame:** at 2 years #### Secondary Outcomes **Description:** Immunohistochemistry tissue analysis. It will allow the evaluation of newly described histological markers for pancreatic adenocarcinoma, which could have a prognostic impact such as the immunophenotype of the inflammatory infiltrate, the expression of the mucins MUC1, MUC5AC, MUC4, MUC16, mesothelin, p53, Ki67 (MIB1) and markers of aggressive subtypes identified by transcriptome studies, in particular the basal-like molecular subtype. **Measure:** Relationship between newly described histological markers for pancreatic adenocarcinoma and patient survival. **Time Frame:** at 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients \> 18 years of age at diagnosis * Primary pancreatic cancer patients operated on in one of the 4 centres between 2001 and 2016 * Histopathological diagnosis of excreto-pancreatic adenocarcinoma of the pancreas, ductal adenocarcinoma or classical adenocarcinoma * Tissue blocks (FFPE) available (tumour/healthy tissue) * Affiliated to a social security scheme Exclusion Criteria: * Absence of Primary Cancer Tissue Blocks (PCTBs) * Paraffin block fixed in Bouin or AFA * Patient Refusal * Pancreatic cancer not corresponding to a conventional excretopancreatic adenocarcinoma such as: carcinoma on intraductal papillary mucinous neoplasm, endocrine tumor/carcinoma, acinar cell carcinoma, ...). * Patient died due to post-surgical complications (death within 30 days post-surgery). * Surgical resection of macroscopic R2 type. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Pancreatic adenocarcinoma patients operated on between 2001 and 2016. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** emmanuelle.leteurtre@chru-lille.fr **Name:** Emmanuelle Leteurtre, MD,PhD **Phone:** 0320445556 **Phone Ext:** +33 **Role:** CONTACT #### Locations **Location 1:** **City:** Lille **Contacts:** ***Contact 1:*** - **Phone:** 0320445962 - **Role:** CONTACT **Country:** France **Facility:** Hop Claude Huriez Chu Lille **Status:** RECRUITING **Zip:** 59037 #### Overall Officials **Official 1:** **Affiliation:** University Hospital, Lille **Name:** Emmanuelle Leteurtre, MD,PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13110 - Name: Pancreatic Neoplasms - Relevance: HIGH - As Found: Pancreas Cancer - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M13102 - Name: Pancreatic Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: T4387 - Name: Pancreatic Cancer - Relevance: HIGH - As Found: Pancreatic Cancer ### Condition Browse Module - Meshes - ID: D000010190 - Term: Pancreatic Neoplasms ### Intervention Browse Module - Browse Branches - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M22554 - Name: Pancrelipase - Relevance: LOW - As Found: Unknown - ID: M13114 - Name: Pancreatin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00771979 **Brief Title:** Relative Bioavailability of Phase II and Phase III Formulations of AZD0530 **Official Title:** A Phase I, Randomised, Open-Label, Cross-Over, Single Centre Study in Healthy Volunteers to Determine the Relative Bioavailability of the Phase III Tablet Formulation to the Phase II Tablet Formulation of AZD0530 #### Organization Study ID Info **ID:** D8180C00033 #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca ### Status Module #### Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2009-06-18 **Type:** ESTIMATED **Last Update Submit Date:** 2009-06-17 **Overall Status:** COMPLETED #### Start Date **Date:** 2008-11 **Status Verified Date:** 2009-06 #### Study First Post Date **Date:** 2008-10-15 **Type:** ESTIMATED **Study First Submit Date:** 2008-10-14 **Study First Submit QC Date:** 2008-10-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Old Name Title:** Mary Stuart, MD, Medical Science Director, Emerging Product Team 1, Oncology **Old Organization:** AstraZeneca Pharmaceuticals ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of the study is to compare how different formulations of AZD0530 are absorbed by the body. As for all clinical trials, safety and tolerability of the drug will be evaluated. ### Conditions Module **Conditions:** - Healthy **Keywords:** - Healthy Volunteers - Relative Bioavailability ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 18 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: AZD0530 **Label:** 1 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** of both the Phase II and Phase III AZD0530 125mg tablet variants (A and B) in a random order. **Name:** AZD0530 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 1 **Description:** Part II: Single doses of AZD0530 125mg oral solution and 2 out of 4 125mg tablet variants (C, D, E and F) in a random order. **Name:** AZD0530 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** To compare the pharmacokinetic parameters for AZD0530 when administered as Phase III formulation in relation to Phase II formulation. **Time Frame:** Pre-dose sample, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168 hours post dose samples. #### Secondary Outcomes **Measure:** To monitor the safety of all subjects by assessment of vital signs, ECG, clinical chemistry, haematology, urinalysis and adverse events. **Time Frame:** From time of consent to last visit. **Measure:** An exploratory objective is to characterise the Pharmacokinetic profile of an oral solution of AZD0530 and 4 additional tablet variants of the Phase III formulation of AZD0530 **Time Frame:** Pre-dose sample, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 120, 168 hours post dose samples. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Female subjects must be of Non- child-bearing potential * Body mass index between 19 and 30 kg/m2 and weigh between 50-100 kg Exclusion Criteria: * Presence of any clinically significant illness * Abnormal vital signs * History of any conditions that may put the subject at risk by participating in the study * Participation in another clinical study. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Alderley Park **Country:** United Kingdom **Facility:** Research Site #### Overall Officials **Official 1:** **Affiliation:** AstraZeneca, Clinical Pharmacology Unit, Alderley Park **Name:** Raj Chetty, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** AstraZeneca,Parklands, Alderley Park **Name:** Mary Stuart, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: Rare - Name: Rare Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M239759 - Name: Saracatinib - Relevance: HIGH - As Found: Fibrin Sealant - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000515233 - Term: Saracatinib ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00202579 **Brief Title:** Efficacy and Safety of Ivabradine in Severe Congestive Heart Failure **Official Title:** Evaluation of the Effects on Peripheral and Central Haemodynamics Parameters, Safety, and Tolerance of Three-hour Intravenous Perfusion (0.1 mg/kg) of Ivabradine Given to Severe Congestive Heart Failure Patients #### Organization Study ID Info **ID:** CL2-16257-053 #### Organization **Class:** INDUSTRY **Full Name:** Servier ### Status Module #### Completion Date **Date:** 2006-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-03-15 **Type:** ACTUAL **Last Update Submit Date:** 2018-03-13 **Overall Status:** COMPLETED #### Start Date **Date:** 2004-09 **Status Verified Date:** 2018-03 #### Study First Post Date **Date:** 2005-09-20 **Type:** ESTIMATED **Study First Submit Date:** 2005-09-12 **Study First Submit QC Date:** 2005-09-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Institut de Recherches Internationales Servier ### Description Module **Brief Summary:** To evaluate the effects on heart function of ivabradine administered to patients with severe chronic heart failure ### Conditions Module **Conditions:** - Heart Failure, Congestive ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE #### Enrollment Info **Count:** 12 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Ivabradine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Haemodynamic parameters **Measure:** Twelve-lead ECG **Measure:** Systolic and diastolic blood pressure #### Secondary Outcomes **Measure:** Echocardiography **Measure:** Neurohormones ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * systolic congestive heart failure * sinus rhythm, HR \>= 80bpm Exclusion Criteria: * unstable cardiovascular condition **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Pavia **Country:** Italy **Facility:** Policlinico San Matteo **Zip:** 27100 #### Overall Officials **Official 1:** **Affiliation:** Policlinico San Matteo **Name:** Luigi Tavazzi, Pr **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **Access Criteria:** Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed. **Description:** Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs). They can ask all interventional clinical studies: * submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope. **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR **IPD Sharing:** YES **Time Frame:** After Marketing Authorisation in EEA or US if the study is used for the approval. **URL:** http://clinicaltrials.servier.com ### References Module #### See Also Links **Label:** Results summary **URL:** http://clinicaltrials.servier.com/wp-content/uploads/CL2-16257-053_synopsis_report.pdf ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00536679 **Brief Title:** Relative Bioavailability and Food Effect Study for GSK163090 in Healthy Male and Female Volunteers **Official Title:** An Open Label, Randomised, Single Dose, Three-way Crossover Study to Investigate the Relative Bioavailability of Two Different Formulations of GSK163090 and the Effect of Food on the Pharmacokinetics of a Tablet Formulation in Healthy Male and Female Volunteers #### Organization Study ID Info **ID:** 103268 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2007-11-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-03 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-11-05 **Type:** ACTUAL #### Start Date **Date:** 2007-09-20 **Type:** ACTUAL **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2007-09-28 **Type:** ESTIMATED **Study First Submit Date:** 2007-09-27 **Study First Submit QC Date:** 2007-09-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study will consist of a screening period, 3 treatment periods and a post-treatment follow-up. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose ### Conditions Module **Conditions:** - Depressive Disorder and Anxiety Disorders **Keywords:** - Relative Bioavailability - Randomised - GSK163090 - Food Effect ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 16 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will be randomized to sequence ABC, where A=1 milligram (mg) GSK163090 Capsule, Fasted, B=1 mg GSK163090 Tablet, Fasted and C=1 mg GSK163090 Tablet, Fed. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose. **Intervention Names:** - Drug: GSK163090 capsule, fasted - Drug: GSK163090 Tablet, fasted - Drug: GSK163090 Tablet, fed **Label:** Sequence ABC **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects will be randomized to sequence ACB, where A=1 mg GSK163090 Capsule, Fasted, B=1 mg GSK163090 Tablet, Fasted and C=1 mg GSK163090 Tablet, Fed. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose. **Intervention Names:** - Drug: GSK163090 capsule, fasted - Drug: GSK163090 Tablet, fasted - Drug: GSK163090 Tablet, fed **Label:** Sequence ACB **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Subjects will be randomized to sequence BAC, where A=1 mg GSK163090 Capsule, Fasted, B=1 mg GSK163090 Tablet, Fasted and C=1 mg GSK163090 Tablet, Fed. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose. **Intervention Names:** - Drug: GSK163090 capsule, fasted - Drug: GSK163090 Tablet, fasted - Drug: GSK163090 Tablet, fed **Label:** Sequence BAC **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Subjects will be randomized to sequence BCA, where A=1 mg GSK163090 Capsule, Fasted, B=1 mg GSK163090 Tablet, Fasted and C=1 mg GSK163090 Tablet, Fed. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose. **Intervention Names:** - Drug: GSK163090 capsule, fasted - Drug: GSK163090 Tablet, fasted - Drug: GSK163090 Tablet, fed **Label:** Sequence BCA **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Subjects will be randomized to sequence CAB, where A=1 mg GSK163090 Capsule, Fasted, B=1 mg GSK163090 Tablet, Fasted and C=1 mg GSK163090 Tablet, Fed. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose. **Intervention Names:** - Drug: GSK163090 capsule, fasted - Drug: GSK163090 Tablet, fasted - Drug: GSK163090 Tablet, fed **Label:** Sequence CAB **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Subjects will be randomized to sequence CBA, where A=1 mg GSK163090 Capsule, Fasted, B=1 mg GSK163090 Tablet, Fasted and C=1 mg GSK163090 Tablet, Fed. In each of the 3 treatment periods, subjects will receive a single oral dose of GSK163090 in the fed or fasted state, followed by a 7-day wash-out period between each dose. **Intervention Names:** - Drug: GSK163090 capsule, fasted - Drug: GSK163090 Tablet, fasted - Drug: GSK163090 Tablet, fed **Label:** Sequence CBA **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Sequence ABC - Sequence ACB - Sequence BAC - Sequence BCA - Sequence CAB - Sequence CBA **Description:** GSK163090 will be available as 1 mg hard gelatine white/white opaque capsules. Each subject will receive a single, oral dose of the study medication on the morning of Day 1. The study drug will be administered with approximately 240 milliliters (mL) of water. **Name:** GSK163090 capsule, fasted **Other Names:** - GSK163090 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Sequence ABC - Sequence ACB - Sequence BAC - Sequence BCA - Sequence CAB - Sequence CBA **Description:** GSK163090 will be available as 1 mg white coated round tablet. Each subject will receive a single, oral dose of the study medication on the morning of Day 1. The study drug will be administered with approximately 240 mL of water. **Name:** GSK163090 Tablet, fasted **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Sequence ABC - Sequence ACB - Sequence BAC - Sequence BCA - Sequence CAB - Sequence CBA **Description:** GSK163090 will be available as 1 mg white coated round tablet. Each subject will receive a single, oral dose of the study medication on the morning of Day 1. The study drug will be administered with Food and Drug Administration (FDA) high fat breakfast. **Name:** GSK163090 Tablet, fed **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Pharmacokinetic parameters for GSK163090. Pharmacokinetic blood samples will be collected up to 72 hours post-dose following each dosing session. **Time Frame:** 72 hours post-dose following each dosing session. #### Secondary Outcomes **Measure:** Additional pharmacokinetic parameters, safety, and tolerability. **Time Frame:** 72 hours post-dose following each dosing session. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy male or female subjects between the ages of 18 and 55 years inclusive. * If female, the subject is eligible to enter and participate in this study if she is not lactating and is of Non-childbearing potential or * Child-bearing potential, has a negative pregnancy test at both screen and baseline and agrees to adequate contraception: * Body weight ≥ 50 kg and body mass index (BMI) between 18.5 - 29.9 kg/m2 inclusive. * Capable of giving informed consent and can comply with the study requirements and timetable. * Self-administered Beck Depression Inventory II scale total score no greater than 9, and suicide question score of zero. * The subject must be able to read, comprehend and record information. * A signed and dated written informed consent is obtained from the subject. * Non-smoker (abstinence from smoking for at least 6 months before the start of the study). * Agrees to abstain from ingesting caffeine or xanthine-containing products for 24 hours prior to the start of dosing until collection of the final pharmacokinetic sample. * Agree to abstain from alcohol for 24 hours prior to the start of dosing until collection of the final pharmacokinetic sample Exclusion Criteria: * As a result of any of the medical interview, physical examination or screening investigations the physician responsible considers the subject unfit for the study. * The subject has a history of a drug or other allergy which in the opinion of the physician responsible contraindicates their participation in the study. * The subject is currently participating or has participated in a clinical trial with a new chemical entity during the previous 4 months or any other trial during the previous 3 months. * The subject has a screening ECG with values outside of protocoled ranges * The subject has a pulse rate \<45 or \>100 bpm and a systolic blood pressure \>150 and \<90 and a diastolic blood pressure \>90 and \<50. * History of long QT syndrome (personal or family) or other cardiac conduction disorder, or other clinically significant cardiac disease. * The subject has liver function tests (LFT) elevated \>1.5 times above the reference range at pre-study screening that remain elevated with a repeat LFT. * Any other clinically significant laboratory abnormality. * Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety. * Abuse of alcohol defined as an average weekly intake of greater than 21 units for males and 14 units for females or an average daily intake of greater than 3 units for males and 2 units for females. 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine. * Consumption of grapefruit juice or grapefruit within 7 days prior to the first dose of study medication until collection of the last PK sample. * The subject is unable to abstain from strenuous physical activity for 48 h prior to screening and follow up and for 48 h prior to and 48 h after each treatment period. * Where participation in study would result in donation of blood in excess of 500 mL within a 90 day period * An unwillingness of male subjects to abstain from, or use adequate contraception during, sexual intercourse with pregnant or lactating women from the time of the first dose of study medication until 90 days following administration of the last dose of study medication OR An unwillingness of the male subject to use a adequate contraception in addition to having their female partner use another form of contraception if the woman could become pregnant from the time of the first dose of study medication until 90 days following administration of the last dose of study medication. * Current or recent (within one year) gastrointestinal disease; a history of malabsorption, esophageal reflux, irritable bowel syndrome; frequent (more than once a week) occurrence of heartburn; or any surgical intervention (e.g., cholecystectomy) which would be expected to influence the absorption of drugs. * The subject has a history of psychiatric illness * Any history of suicidal attempts or behavior. * The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen. * The subject has tested positive for HIV. * The subject has a past history of drug abuse or has tested positive for urine drugs of abuse at pre-study screening. * The subject has any history of serotonin syndrome. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Neuss **Country:** Germany **Facility:** GSK Investigational Site **State:** Nordrhein-Westfalen **Zip:** 41460 #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7058 - Name: Depression - Relevance: LOW - As Found: Unknown - ID: M4324 - Name: Anxiety Disorders - Relevance: HIGH - As Found: Anxiety Disorder - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depressive Disorder - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003866 - Term: Depressive Disorder - ID: D000001008 - Term: Anxiety Disorders ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04577079 **Brief Title:** Klinik - Intelligent Patient Flow Management **Official Title:** Validation of Intelligent Patient Flow Management System in Kuopio University Hospital Emergency Department #### Organization Study ID Info **ID:** KUH507P004 #### Organization **Class:** OTHER **Full Name:** Kuopio University Hospital ### Status Module #### Completion Date **Date:** 2022-11-18 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-10-31 **Type:** ACTUAL #### Start Date **Date:** 2020-09-01 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2020-10-06 **Type:** ACTUAL **Study First Submit Date:** 2020-09-03 **Study First Submit QC Date:** 2020-09-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Kuopio University Hospital #### Responsible Party **Investigator Affiliation:** Kuopio University Hospital **Investigator Full Name:** Tero Martikainen **Investigator Title:** Head physician of Emergency Care Department **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Digital health technologies (DHT) are increasingly developed to support healthcare systems around the world. However, they are frequently lacking evidence-based medicine and medical validation. There is considerable need in the western countries to allocate healthcare resources accurately and give the population detailed and reliable health information enabling to take greater responsibility for their health. Intelligent patient flow management system (IPFM, product name Klinik Frontline) is developed to meet these needs. In practice, IPFM is used for decision support in the triaging and diagnostic processes as well as automatizing the management of inflow of the patients. The core of the IPFM is a clinical artificial intelligence (AI), which utilizes a comprehensive medical database of clinical correlations generated by medical doctors. The study population of this research consists of patients from the Emergency Department of Kuopio University Hospital (KUH). Data will be gathered during 2 weeks of piloting, after which the results will be analysed. Anticipated number of patients to the study is minimum of 246 patients, with objective to be several hundreds. When attending to the hospital, patients will report their demographics, background information and symptoms using structured IPFM online form. Patients entering the unit in an ambulance or with need of immediate care of healthcare professionals due to severe and acute conditions are referred similar to normal process to ensure the patient safety. Results obtained from IPFM are blinded from the healthcare professional and IPFM does not affect professional's clinical decision making in any way. The data obtained from IPFM online form and clinical data from the emergency department and KUH will be analysed after the data collection. The main aim of the research is to validate the use of IPFM by evaluating the association of IPFM output with 1) urgency and severity of the conditions (using Emergency Severity Index \[ESI\], an international triaging protocol for emergency units, and an assessment by triage nurse); and 2) actual diagnoses diagnosed by medical doctors. The main hypotheses of the research are that 1) IPFM is safe and sensitive in evaluating the urgency of the conditions of arriving patients at the emergency department and that 2) IPFM has sufficient correlation of differential diagnosis with actual diagnosis made by medical doctor. **Detailed Description:** 1. Background Continuous development of digital technology provides new opportunities also in healthcare area. As healthcare costs are constantly growing both worldwide and in Finland (1), innovations are needed to enhance allocation of limited healthcare resources and to reduce economic burden. Digital health technologies (DHT) have the potential to reduce these costs. They are increasingly developed to support healthcare systems around the world. DHT are, however, often lacking evidence-based medicine (2) and both the importance and the lack of their validation has been acknowledged widely (3, 4). Work in triage and urgent care centers is highly demanding, with considerable time pressure. When operating with high patient volumes, acute conditions and severe stress, human errors are likely to result at least at some extent. Physicians have been found to have a \~5 % diagnostic error rate (5) with half of these potentially harmful (6). DHT have been suggested to have a significant role helping both patient management and triage (7), and thus, reducing also potential human errors. For instance, crude online clinical decision support tool has been found to reliably demonstrate emergency triage severity in experimental setting (7). The validation of DHT and decision support tools is highly crucial. Tools with false negative rates could have serious consequences when ignoring severe conditions such as cardiac ischaemia (4). DHT should be thorough and optimal in the medical field and their internal and external validity should have been evaluated. Recently, guidelines for evaluating DHT have been published (4). According to guidelines, the first step in the assessment is to show the results in an early observational study in clinical setting. In addition to safety, also efficacy and effectiveness of DHT should be evaluated. To meet these needs, Intelligent Patient Flow Management system (IPFM) has been developed to help the user (i.e. patient) and the healthcare professionals to evaluate user's condition and its severity. IPFM enables semi-automated triaging of patients and enhances the management of patient inflow and demand. In addition, IPFM provides written and precise information for the healthcare professionals communicated by the patients themselves of their conditions and symptoms. The core of IPFM is a broad medical database generated by medical doctors, combined with artificial intelligence (AI) and feedback loops for accuracy improvement. In other words, IPFM is an AI-induced triage and decision support tool developed and monitored by medical doctors to help healthcare professionals to evaluate the urgency of the patients. It evaluates user's condition and infers the urgency using user demographics, background information and symptoms. The IPFM is developed by a healthcare technology company Klinik Healthcare Solutions Oy and it has already been implemented in over 400 primary care and dental facilities in the Nordics and was recently launched in the United Kingdom and Portugal. It has been previously shown to reduce the costs in primary care by 14 % in overall total service costs of the patients by streamlining the patient flow (8). IPFM is currently classified and registered as a CE class 1 medical device, which requires continuous scientific validation research and systematic development and quality management processes. The system is used according to its intended use in this study and therefore the study does not require permission or registration for FIMEA's clinical device study register. Klinik's IPFM (product names Klinik Access, Klinik Frontline) provides a full-stack solution, with interface for patient input, backend for database and algorithm calculations and interface for handling of case outputs for triaging and combined statistics for healthcare staff. IPFM uses medically golden standard Bayesian methodology for inferring the effect of clinical features on the probabilities of the conditions. The severity and the urgency of the condition is inferred using specific severity symptoms and by setting a threshold for the probabilities of relevant conditions. All inflow of data is dynamically gathered and analysed ensemble and visualised, which can be used by (management) staff to monitor and optimally meet demand ad hoc. 2. Aims and objectives The main aim of this study is to validate the use of IPFM in a hospital setting by evaluating the association of IPFM output with 1) clinical urgency and severity of the conditions (using Emergency Severity Index \[ESI\], an international triaging protocol for emergency units, and an assessment by triage nurse); and 2) actual diagnoses made by the hospital doctors. The objective is also to assess the correlation of IPFM output with redirection or referral to various specialties (e.g. internist or surgeon). Main hypotheses are: * IPFM is safe (\< 1 % emergency cases missed) and accurate (\> 80 % agreement with triaging nurse) in evaluating the urgency of the conditions of arriving patients at the emergency department * IPFM has sufficient correlation (\> 60 % overlap) of differential diagnosis with actual diagnosis diagnosed by medical doctor Validating IPFM, an AI-induced triage support and decision support tool, in real-life environment and in hospital setting is essential for its use in hospitals and clinical work in the future to support evidence-based medicine. An accurate and efficient tool will decrease delays of treatment of urgent conditions and has the potential to decrease human errors that are inevitable in environment with high patient volumes, acute conditions and severe stress. When in full implementation, it can also help to optimize emergency department resources and to target them more accurately. In addition, this study provides important information on patient history and symptoms provided by patients themselves when entering emergency department compared to clinical data. 3. Materials and methods The study population consists of patients entering the emergency department of Kuopio University Hospital (KUH) during a 2-week research period. The calculated needed sample size is a minimum of 246 patients (confidence level 95%, margin of error 5%, study population proportion 80%). The data consists of registry data from the electronic health records, other quantitative data (such as extracts from KUH emergency department reporting software) and qualitative data acquired through observation. Both qualitative and statistical methods will be applied to the data to infer outcomes. Case-specific information in the IPFM (demographics, background information, symptoms) provided by the patient will be analyzed with clinical data (Emergency Severity Class index (ESI), triage category, diagnoses) collected from the electronic patient records of the hospital (emergency and other possible departments) and IPFM professional dashboard, and the safety, specificity and sensitivity of IPFM output are analyzed. The urgency of the condition is evaluated by IPFM and the analyses with clinical data and validation will be performed after the data collection. They urgency is evaluated by IPFM as: 1. suitable for self-care if no prescription medication or other treatment is suggested (i.e. doesn't require doctor's evaluation, however might benefit from nurse check-up and advice); 2. non-urgent if ailment is prolonged or chronic, but benefits from doctor's evaluation and would more efficiently be managed through non-urgent appointment (\> 3 days); 3. urgent if ailment is (semi-)acute and benefits from doctor's evaluation within 1-3 days; and 4. emergency if ailment requires evaluation and treatment within the same day (or immediately) to avoid risk of serious health hazard. This output is correlated with the ESI classification used by KUH emergency and other data collected from electronic health records regarding urgency of the condition. When attending to the hospital, patients will report their demographics, background information, symptoms, other case specific data and satisfaction using structured IPFM online form. Patients entering the unit in an ambulance or with need of immediate care due to severe and acute conditions are managed through traditional process: they do not fill the form and, hence, are out of scope of the pre-evaluation process and this study. All information gathered is transferred to the IPFM dashboard, where the patient reported clinical information, AI-induced suggestions on the urgency of the care needed and potential diagnosis (a differential of 3-10 probable diagnosis) is demonstrated. However, in this study design, healthcare professionals cannot see any clinical information in the IPFM dashboard, i.e. the output of IPFM is blinded. Patient data will be saved to the registry from IPFM: 1) age; 2) gender; 3) duration of the symptoms; 4) body location of the symptoms; 5) symptoms chosen from the symptom cloud(s) by the patient (symptom cloud is dynamic, consist of 430 potential symptoms, symptom selection varies depending on the previous actions of the patient); 6) severity symptoms chosen from the severity symptom cloud (severity symptom cloud is dynamic, consist of 100 potential severity symptoms, selection varies depending on the previous actions of the patient); 7) free text fields regarding the selected symptoms; 8) answers (yes/no) to the questions: a) have you used any medication or other treatment for your ailment, b) has someone (e.g. a physician or a physiotherapist) already examined or treated your ailment; 9) identification number of the form; 10) unique case id number; 11) name; 12) social security number; and 13) telephone number. After the primary IPFM data collection stage at the beginning of each ER visit, a secondary stage of data retrieval is initiated after the study period. During this only critical information required to assess the validity of the IPFM system outcomes will be fetched from the electronic health care system: 1) ESI classification; 2) diagnosis/diagnoses of the patient; 3) speciality \& care path chosen in the urgency care; 4) traditional non-ESI urgency assessment comparable to our urgency scale (if stored). The final data points will be equivalent to these, but might due to changes in ER practices and/or data systems vary. The data points are chosen to optimally allow comparative analysis of results. This information is only used after data collection when evaluating the validity of IPFM. Despite excluding patients with need of acute immediate care of healthcare professionals (arriving with an ambulance), also children/adolescents and patients with otherwise restricted capabilities or developmental disorders are excluded from the study. Adult patients with mild mental disorders can be included, excluding the patients with guardian. Additionally, pregnant or breastfeeding patients are excluded from the study. 4. Ethical aspects of the research Participation to the study is voluntary for the patients. After receiving oral and written information on location at KUH emergency department, patients will sign an informed consent form. As described in the chapter 5, the study protocol will not harm any study subjects and will not interfere negatively in their treatment. The patients participate in the study only once, on location when arriving to the emergency department, and thus no further activity nor financial burden is generated. An independent research data registry will be generated for this study. When creating the registry, social security number or telephone number is used to merge the data from electronic health records and IPFM. After the data has been merged and the combined registry is created, randomly generated case ids are used as research subject identifiers and information that allows for identification of single patients is not available. The merging of the data is done by the KYS staff prior to access into research registry being granted for the research group. The combined research registry will be stored in a digital format, on a computer owned only by the research group members. There will be a password protection for a user to enter a) the computer and b) the registry file itself. The file will be stored on a local folder not accessed online (i.e. not a cloud storage folder). The registry file will be stored for five (5) years after the research has deemed finished and will be deleted after the period according to the required handling standards. The administrator of the case ids is the person responsible of the project and Klinik Healthcare Solutions Oy is responsible for storing the registry file. The study will be registered into international "ClinicalTrials.gov" research register. The results of this project will be reported in a group level and, thus, no individual information can be recognized. The application for the ethical committee will be submitted in May 2020. 5. Risk assessment The healthcare professionals are evaluating the patients by their own clinical judgement and they do not utilize output of IPFM in their decision making. IPFM data is only assessed after the data collection. There is a potential risk of acquiring volunteers below the intended volume for the study. This will be addressed by extending the study period or overlap of daily working hours. There is a hypothetical risk of causing undesired delay in the registration process of the patients that would cause critical cases to be missed due to increased waiting times for the registration. Our previous user studies have shown that filling out the IPFM form takes circa 3-5 minutes, which would not be a life threatening delay for walk-in patients. This risk will be monitored and if noticed, managed in real time. 6. Time schedule and funding plans This study is initially planned to be executed between 1.7.2020 and 30.6.2023. Duration of the data collection is approximately 2 weeks and is designed to complete during fall 2020. The project is anticipated to have a small scale economic effect for the parties. The patients in this study will not experience any economic harm. The service provider Klinik Healthcare Solutions Oy will cover for the costs of it's researchers and assisting staff in the form of a moderate hourly pay. The service provider will also provide the digital equipment used in the research in collecting the information from the patients. In the approval of the equipment it will work closely with the ICT department of Kuopio University Hospital District. The hospital or the emergency department will not have any additional costs regarding the research project. There are no additional economical compensations to the researchers or to the study population. 7. Research group, resources and conflicts of interest The research group consists of MD, PhD Juhani Määttä (Medical Research Center Oulu, University of Oulu), MD, PhD candidate Petteri Hirvonen (University of Helsinki), MD Rony Lindell (University of Helsinki) and PhD Tero Martikainen, chief doctor of Kuopio University Hospital A\&E department. Juhani Määttä, Petteri Hirvonen and Rony Lindell have financial and business interests in Klinik Healthcare Solutions Oy. 8. Expected results and scientific impact The study is expected to validate high accuracy (i.e. safe and reliable usability) of IPFM tool in KUH hospital context. The results are generalizable to other hospital emergency departments, however with caution by doing contextual analysis and process comparisons prior to implementation considerations. Through assessing IPFM output with data from patient's electronic health records, the study is expected to show: 1) strong correlation of the urgency category; and 2) good correlation between calculated differential diagnosis and the diagnoses of ED or ward doctors. The purpose is to publish the results in internationally recognized medical journals with high quality. According to our review of the literature on this subject, an AI-supported automation of the inbound patient traffic in an emergency department setting has not been studied previously, especially not in this scale and patient variation. An increasing public and professional interest is arising regarding AI-based solutions to support professionals in their work and decision making. To meet these needs, this study provides and scientifically validates a solution which works semi-independently, taking up initial tasks normally reserved for healthcare professionals. The research group anticipates this being of great interest to the scientific community - and will add to the discussion of the possibilities of the DHT to provide marked cost-effectiveness while not compromising on patient safety and effectiveness of the use of professional resources. ### Conditions Module **Conditions:** - Emergency Medical Services **Keywords:** - Intelligent patient flow management ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 273 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patient screened and assessed by intelligent patient flow management system. **Intervention Names:** - Device: Evaluation of the need of emergency medical services **Label:** IPMF Screened ### Interventions #### Intervention 1 **Arm Group Labels:** - IPMF Screened **Description:** The main aim of this study is to validate the use of IPFM in a hospital setting by evaluating the association of IPFM output with 1) clinical urgency and severity of the conditions (using Emergency Severity Index \[ESI\], an international triaging protocol for emergency units, and an assessment by triage nurse); and 2) actual diagnoses made by the hospital doctors. The objective is also to assess the correlation of IPFM output with redirection or referral to various specialties **Name:** Evaluation of the need of emergency medical services **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The number of missed emergency cases evaluated by IPFM. **Measure:** Specificity (%) of intelligent patient flow management (IPFM) correlated with the evaluation of trained emergency (triage) nurse. **Time Frame:** Through study completion, estimated until the end of 2020. **Description:** The number of correct emergency severity index (ESI) class **Measure:** Sensitivity (%) of intelligent patient flow management (IPFM) correlated with the evaluation of trained emergency (triage) nurse. **Time Frame:** Through study completion, estimated until the end of 2020. #### Secondary Outcomes **Description:** IPFM correlation of differential diagnosis with actual diagnosis diagnosed by medical doctor **Measure:** Correlation (%) of differential diagnosis **Time Frame:** Through study completion, estimated until the end of 2020. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: All adult (\>18 years of age) patients independently (walking) entering emergency care ward with written consent. Exclusion Criteria: * Patients arriving with ambulance * Patients needing immediate care * Patients under 18 years of age * Patients with restricted capabilities or developmental disorders. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients living in the district of North-Savo (250 000). ### Contacts Locations Module #### Locations **Location 1:** **City:** Kuopio **Country:** Finland **Facility:** Kuopio university hospital **State:** Eastern-Finland **Zip:** 70029 #### Overall Officials **Official 1:** **Affiliation:** Kuopion University Hospital, Emergency medicine **Name:** Tero J Martikainen, MD. PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Greaves F, Joshi I, Campbell M, Roberts S, Patel N, Powell J. What is an appropriate level of evidence for a digital health intervention? Lancet. 2019 Dec 22;392(10165):2665-2667. doi: 10.1016/S0140-6736(18)33129-5. Epub 2018 Dec 10. No abstract available. Erratum In: Lancet. 2019 Dec 22;392(10165):e18. **PMID:** 30545779 **Citation:** The Lancet. Is digital medicine different? Lancet. 2018 Jul 14;392(10142):95. doi: 10.1016/S0140-6736(18)31562-9. No abstract available. **PMID:** 30017135 **Citation:** Fraser H, Coiera E, Wong D. Safety of patient-facing digital symptom checkers. Lancet. 2018 Nov 24;392(10161):2263-2264. doi: 10.1016/S0140-6736(18)32819-8. Epub 2018 Nov 6. No abstract available. **PMID:** 30413281 **Citation:** Singh H, Meyer AN, Thomas EJ. The frequency of diagnostic errors in outpatient care: estimations from three large observational studies involving US adult populations. BMJ Qual Saf. 2014 Sep;23(9):727-31. doi: 10.1136/bmjqs-2013-002627. Epub 2014 Apr 17. **PMID:** 24742777 **Citation:** Singh H, Giardina TD, Meyer AN, Forjuoh SN, Reis MD, Thomas EJ. Types and origins of diagnostic errors in primary care settings. JAMA Intern Med. 2013 Mar 25;173(6):418-25. doi: 10.1001/jamainternmed.2013.2777. **PMID:** 23440149 **Citation:** Elias P, Damle A, Casale M, Branson K, Churi C, Komatireddy R, Feramisco J. A Web-Based Tool for Patient Triage in Emergency Department Settings: Validation Using the Emergency Severity Index. JMIR Med Inform. 2015 Jun 10;3(2):e23. doi: 10.2196/medinform.3508. Erratum In: JMIR Med Inform. 2015 Jun 15;3(3):e24. **PMID:** 26063343 **Citation:** Tenhunen H, Hirvonen P, Linna M, Halminen O, Horhammer I. Intelligent Patient Flow Management System at a Primary Healthcare Center - The Effect on Service Use and Costs. Stud Health Technol Inform. 2018;255:142-146. **PMID:** 30306924 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7796 - Name: Emergencies - Relevance: HIGH - As Found: Emergency - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004630 - Term: Emergencies ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01653379 **Brief Title:** A Phase 2A Dose-ranging and Pharmacokinetic Study of an Oral Vitamin D Compound (DP001) in Secondary Hyperparathyroidism **Official Title:** A Phase 2A, Open-label, Dose-ranging and Pharmacokinetic Study of an Oral Vitamin D Compound (DP001) in Secondary Hyperparathyroidism in Patients on Hemodialysis #### Organization Study ID Info **ID:** 2MD-7H-2A #### Organization **Class:** INDUSTRY **Full Name:** Deltanoid Pharmaceuticals ### Status Module #### Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Disp First Post Date **Date:** 2017-08-16 **Type:** ACTUAL **Disp First Submit Date:** 2017-08-14 **Disp First Submit QC Date:** 2017-08-14 #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-16 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Start Date **Date:** 2012-08 **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2012-07-31 **Type:** ESTIMATED **Study First Submit Date:** 2012-07-25 **Study First Submit QC Date:** 2012-07-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Deltanoid Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is an open-label, dose-ranging study of the vitamin D analog DP001 in patients with end-stage renal disease (ESRD). The primary goals of this 4-week Phase 2A study are to identify an appropriate starting dose of DP001 to be used in subsequent studies in this population and for evaluation of pharmacokinetics of DP001 in ESRD patients. **Detailed Description:** Vitamin D hormone or analogs, when bound to the vitamin D receptor, suppress PTH synthesis by binding to a negative regulatory element in the promoter of the PTH gene, and have been used successfully in the clinic to reduce elevated PTH levels in dialysis patients and other CKD patients. DP001 is a highly potent vitamin D compound. In two clinical trials testing DP001 in postmenopausal women, oral DP001 reduced PTH levels in a dose-dependent manner, with a dose of 220 ng lowering PTH by at least 30% in a majority of patients following one or six months of daily dosing. This study is an open-label, dose-ranging study of DP001 in ESRD patients with secondary hyperparathyroidism. Cohorts of up to 6 patients will be enrolled and administered oral DP001 at 110 ng three times per week for four weeks. Laboratory data from each cohort will be assessed and used to determine a dose for the next cohort. Up to 5 dose-ranging cohorts will be studied, with the goal of identifying an appropriate dose for a randomized, placebo-controlled study of oral DP001 for 12 weeks. The data will also be used to select an appropriate dose for an additional cohort of 12 open-label patients in the current study in which the pharmacokinetics of DP001 following a single dose and after repeated doses will be studied. ### Conditions Module **Conditions:** - Secondary Hyperparathyroidism ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 42 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** DP001 softgel capsules; 55 ng to 550 ng per dose, administered 3 times weekly for 4 weeks **Intervention Names:** - Drug: DP001 **Label:** DP001 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - DP001 **Description:** DP001 softgel capsules; 55 ng to 550 ng per dose, administered 3 times weekly for 4 weeks **Name:** DP001 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change in intact parathyroid hormone levels in blood **Time Frame:** Baseline and 4 weeks #### Secondary Outcomes **Description:** 1, 2, 4, 8, 24, and 48 hours following a single dose; 1, 2, 4, 8, 24, 48, 72, and 96 hours following multiple doses **Measure:** Blood levels of DP001 **Time Frame:** Multiple time points following single dose and 4 weeks of dosing ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient is diagnosed with ESRD and must be on hemodialysis 3 times per week for at least 3 months * Plasma intact PTH value \>/= 300 pg/mL Exclusion Criteria: * Currently taking drugs affecting vitamin D metabolism * History of symptomatic ventricular dysrhythmias, congestive heart failure, angina pectoris, myocardial infarction, coronary angioplasty, or coronary artery bypass grafting * Active malignancy * Clinically significant liver disease * Active infections **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tucson **Country:** United States **State:** Arizona **Location 2:** **City:** Tustin **Country:** United States **State:** California **Location 3:** **City:** Denver **Country:** United States **State:** Colorado **Location 4:** **City:** Saint Louis **Country:** United States **State:** Missouri **Location 5:** **City:** Greenville **Country:** United States **State:** Texas **Location 6:** **City:** Madison **Country:** United States **State:** Wisconsin #### Overall Officials **Official 1:** **Affiliation:** Massachusetts General Hospital **Name:** Ravi Thadhani, MD **Role:** STUDY_CHAIR ### References Module #### See Also Links **Label:** To obtain contact information for a study center near you, click here: **URL:** http://deltanoid.com/contact.php ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009385 - Term: Neoplastic Processes - ID: D000009369 - Term: Neoplasms - ID: D000010335 - Term: Pathologic Processes - ID: D000010279 - Term: Parathyroid Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC19 - Name: Gland and Hormone Related Diseases ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Secondary - ID: M10012 - Name: Hyperparathyroidism - Relevance: HIGH - As Found: Hyperparathyroidism - ID: M10013 - Name: Hyperparathyroidism, Secondary - Relevance: HIGH - As Found: Secondary Hyperparathyroidism - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown - ID: M13192 - Name: Parathyroid Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000006961 - Term: Hyperparathyroidism - ID: D000006962 - Term: Hyperparathyroidism, Secondary ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: T442 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: T479 - Name: Vitamin D3 - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05483179 **Brief Title:** Association Between New Effort-independent Cardiopulmonary Exercise Test Variables and Postoperative Complications After Elective Colorectal Surgery **Official Title:** Association Between New Effort-independent Cardiopulmonary Exercise Test Variables and Postoperative Complications After Elective Colorectal Surgery #### Organization Study ID Info **ID:** 2022_052a #### Organization **Class:** OTHER **Full Name:** VieCuri Medical Centre ### Status Module #### Completion Date **Date:** 2022-07-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-08-02 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-07-15 **Type:** ACTUAL #### Start Date **Date:** 2022-04-15 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2022-08-02 **Type:** ACTUAL **Study First Submit Date:** 2022-07-28 **Study First Submit QC Date:** 2022-07-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** VieCuri Medical Centre #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A cardiopulmonary exercise test (CPET) is increasingly used for preoperative risk assessment. Oxygen uptake (VO2) at peak exercise (VO2peak) and VO2 at the ventilatory anaerobic threshold (VO2VAT) are the most commonly used preoperative CPET variables that are associated with postoperative outcomes following colorectal cancer surgery. The aim of this study is to investigate the association between two relatively new preoperative submaximal and effort-independent CPET variables, the cardiopulmonary optimal point (COP) and the Oxyen uptake efficiency plateau (OUEP) and postoperative outcomes in colorectal cancer surgery. In additiion, the association between the oxygen uptake at the COP en OUEP and postoperative outcomes wil be explored. **Detailed Description:** After resection for colorectal carcinoma, \>30% of the patients develop a complication during admission or within 30 days after surgery. Several studies indicate that preoperative aerobic fitness, as objectively measured by a maximal cardiopulmonary exercise test, is associated with postoperative complications, in which a lower aerobic fitness indicates a higher risk for complications. The most used CPET variables, oxygen uptake (VO2) at peak exercise (VO2peak) and VO2 at the ventilatory anaerobic threshold (VO2VAT), have specific limitations. For a valid VO2peak, a maximal effort is required and VO2VAT determination is subjective and cannot be determined in all patients. Therefore, this study aims to explore the association of submaximal (effort-independent) preoperative CPET variables that are determinable in all patients, specifically the relation between the cardiopulmonary optimal point (COP) and the oxygen uptake efficiency plateau (OUEP), and postoperative outcomes in patient undergoing colorectal surgery. Participants An explorative study will be carried out using retrospectively collected data from patients who underwent preoperative CPET in Medisch Spectrum Twente (MST), Máxima Medical Center (MMC), Maastricht University Medical Center+ (MUMC+), and VieCuri Medical Center (VMC). Patient characteristics and outcome measures The following baseline patient characteristics will be collected: sex, age, body height, body mass, body mass index (BMI), nutritional status assessed by the short nutritional assessment questionnaire (SNAQ) score, smoking status (current, former, never), use of beta-blocker (yes/no), veterans-specific activity questionnaire score, location, type and stage of the tumor, American Society of Anesthesiologists (ASA) score (I-IV), Charlson comorbidity index (divided into three groups: 0, 1, and 2+), and type of surgical resection. CPET data will be interpreted by two trained and experienced clinical exercise physiologists. The variables VO2peak, VO2VAT, COP, and OUEP as well as the oxygen uptake at the COP and OUEP will be determined. Outcome measures of interest are postoperative complications within 30 days after surgery and length of hospital stay. The severity of any postoperative complication will be scored using the Clavien-Dindo classification of complications (grade 1-5). A postoperative complication is defined as a Clavien Dindo grade of 1 or higher. A grade 3-5 complication is defined as a severe complication. Statistical analysis Receiver operator curve (ROC) analysis will be used to assess the independent ability of the VO2peak (mL/kg/min), VO2VAT (mL/ kg/min), COP, oxygen uptake at the COP, OUEP and and oxygen uptake at the OUEP to discriminate between patients with and without 30-day postoperative complications. The optimal cut-off point is based on our preference to have primarily a high sensitivity (\>0.8) with a reasonable specificity (\>0.5), as we aim to detect almost all high-risk patients that might benefit from a preoperative intervention (e.g., exercise prehabilitation). Forward stepwise multivariable logistic regression analyses will be performed to investigate the prognostic value of the beforementioned CPET variables and 30-day postoperative complications separately for all complications (Clavien-Dindo grade of 1 or higher) and severe complication (Clavien-Dindo grade of 3-5). In case the baseline demographics are associated with 30-day postoperative complications (p\<0.200), they will be tested for their association with VO2peak, VO2VAT, VE/VCO2-slope, and OUES/kg (p\<0.200) using Pearson's r or Spearman's rho correlation coefficients, or paired sample t-tests, Mann Whitney U test, or one-way ANOVA, as appropriate. The logistic regression models will be adjusted for the potential confounders in a forward stepwise procedure. Based on the optimal cut of points extracted from the ROC curves for each CPET variable, Data will be analyzed with the Statistical Package for the Social Sciences for Windows (version 23.0; IBM, SPSS Inc., Chicago, IL, USA). Continuous data will be presented as mean with standard deviation, or as median with interquartile range (IQR), as appropriate. Categorical data will be summarized by frequency and percentage. A p-value \<0.05 will be considered statistically significant. ### Conditions Module **Conditions:** - Colorectal Cancer ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 116 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Diagnostic Test: Preoperative cardiopulmonary exercise tetsing Patients underwent a cardiopulmonary exercise test prior to surgery. **Intervention Names:** - Diagnostic Test: CPET **Label:** Patients with colorectal cancer Patients with colorectal cancer who underwent elective surgery. ### Interventions #### Intervention 1 **Arm Group Labels:** - Patients with colorectal cancer Patients with colorectal cancer who underwent elective surgery. **Description:** Cardiopulmonary exercise test **Name:** CPET **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Postoperative complications scored using Clavien-Dindo clasification gade (1-5) **Measure:** Postoperative complications **Time Frame:** 30 days postoperative #### Secondary Outcomes **Description:** Length of hospital stay in days **Measure:** Length of stay **Time Frame:** 60 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Patients who had a preoperative CPET and who underwent elective colorectal surgery and where, \> 18 years (MMC, VMC) or ≥60 years (MST), with a score ≤7 metabolic equivalents on the veterans-specific activity questionnaire (MST, MUMC+,VMC). Exclusion Criteria: Patients who participated in exercise prehabilitation prior to surgery **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with colorectal cancer stage I-III sceduled for surgery ### Contacts Locations Module #### Locations **Location 1:** **City:** Venlo **Country:** Netherlands **Facility:** Viecuri medical center **State:** Limburg **Zip:** 5995BL ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14065 - Name: Postoperative Complications - Relevance: HIGH - As Found: Postoperative Complications ### Condition Browse Module - Meshes - ID: D000011183 - Term: Postoperative Complications ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00045279 **Brief Title:** PEG-Interferon Alfa-2b in Treating Patients With Metastatic Kidney Cancer **Official Title:** Phase II Trial of PEG-Intron in Patients With Advanced Renal Cell Carcinoma #### Organization Study ID Info **ID:** 01-143 #### Organization **Class:** OTHER **Full Name:** Memorial Sloan Kettering Cancer Center #### Secondary ID Infos **Domain:** PDQ (Physician Data Query) **ID:** CDR0000256464 **Type:** REGISTRY **ID:** NCI-G-02-2102 ### Status Module #### Completion Date **Date:** 2005-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-06-05 **Type:** ESTIMATED **Last Update Submit Date:** 2013-06-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2005-09 **Type:** ACTUAL #### Start Date **Date:** 2002-04 **Status Verified Date:** 2013-06 #### Study First Post Date **Date:** 2003-01-27 **Type:** ESTIMATED **Study First Submit Date:** 2002-09-06 **Study First Submit QC Date:** 2003-01-26 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** Memorial Sloan Kettering Cancer Center ### Description Module **Brief Summary:** RATIONALE: PEG-interferon alfa-2b may stop the growth of kidney cancer by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of PEG-interferon alfa-2b in treating patients who have metastatic kidney cancer. **Detailed Description:** OBJECTIVES: * Determine the efficacy of PEG-interferon alfa-2b in patients with metastatic renal cell carcinoma. * Determine the time to disease progression in patients treated with this drug. * Determine the safety of this drug in these patients. * Determine the quality of life of patients treated with this drug. * Determine the effect of this drug on biological surrogates of antitumor activity (basic fibroblast growth factor, vascular endothelial growth factor, and interleukin-6 serum levels) in these patients. OUTLINE: Patients receive PEG-interferon alfa-2b subcutaneously once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at 2 weeks and at 2, 4, 8, and 12 months after initiation of study therapy, and then at completion of study therapy. PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 15 months. ### Conditions Module **Conditions:** - Kidney Cancer **Keywords:** - stage IV renal cell cancer ### Design Module #### Design Info ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** PEG-interferon alfa-2b **Type:** BIOLOGICAL ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: * Histologically confirmed renal cell carcinoma * Metastatic disease * No prior therapy for advanced disease * Tumor sample available for molecular analysis with prior registration on MSKCC IRB # 89-076 * Bidimensionally measurable disease * No brain metastases unless completely resected and without evidence of recurrence for at least six months PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 70-100% Life expectancy * Not specified Hematopoietic * WBC at least 3,000/mm3 * Platelet count at least 100,000/mm3 Hepatic * Bilirubin no greater than 1.5 mg/dL * SGOT no greater than 2.5 times upper limit of normal (unless due to hepatic metastases) * Hepatitis B surface antigen negative * Hepatitis C negative Renal * Creatinine no greater than 2 mg/dL Cardiovascular * No severe cardiac disease * No New York Heart Association class III or IV cardiac disease * No myocardial infarction within the past 12 months * No ventricular tachyarrhythmias requiring ongoing treatment * No unstable angina Pulmonary * No severe asthma requiring chronic systemic steroids Other * HIV negative * Negative pregnancy test * Fertile patients must use effective contraception * No malignancy within the past 2 years except basal cell or squamous cell skin cancer, superficial bladder cancer, or localized prostate cancer * Patients who have undergone potentially curative therapy and have been deemed to be at low risk for recurrence are eligible * No medically significant psychiatric disease (e.g., endogenous depression, psychosis, or bipolar disease) requiring hospitalization * No prior or active autoimmune disease * Medically controlled diabetes or thyroid dysfunction allowed * No clinically significant acute viral or bacterial infection that requires specific therapy PRIOR CONCURRENT THERAPY: Biologic therapy * No prior interleukin-2 * No prior interferon alfa * No concurrent cytokines or biological response modifiers except epoetin alfa in the case of hematologic compromise * No concurrent tumor vaccines * No concurrent monoclonal antibodies * No concurrent bone marrow/stem cell transplantation Chemotherapy * No concurrent cytotoxic agents Endocrine therapy * No concurrent high-dose systemic steroids * Concurrent low-dose corticosteroids (e.g., asthma inhalers, topical creams, or intra-articular injections) allowed * No concurrent hormonal therapy (including megestrol) * Concurrent hormone replacement therapy or oral contraceptives allowed Radiotherapy * At least 4 weeks since prior radiotherapy * No concurrent radiotherapy Surgery * See Disease Characteristics * At least 4 weeks since prior major surgery * Concurrent nephrectomy allowed Other * At least 14 days since prior anti-infectious therapy * No other concurrent investigational drugs **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New York **Country:** United States **Facility:** Memorial Sloan-Kettering Cancer Center **State:** New York **Zip:** 10021 #### Overall Officials **Official 1:** **Affiliation:** Memorial Sloan Kettering Cancer Center **Name:** Robert J. Motzer, MD **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Feldman DR, Kondagunta GV, Schwartz L, Patil S, Ishill N, DeLuca J, Russo P, Motzer RJ. Phase II trial of pegylated interferon-alpha 2b in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2008 Mar;6(1):25-30. doi: 10.3816/cgc.2008.n.004. **PMID:** 18501079 **Citation:** Motzer RJ, Rakhit A, Thompson J, Gurney H, Selby P, Figlin R, Negrier S, Ernst S, Siebels M, Ginsberg M, Rittweger K, Hooftman L. Phase II trial of branched peginterferon-alpha 2a (40 kDa) for patients with advanced renal cell carcinoma. Ann Oncol. 2002 Nov;13(11):1799-805. doi: 10.1093/annonc/mdf288. **PMID:** 12419754 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014571 - Term: Urologic Neoplasms - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000000230 - Term: Adenocarcinoma - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5548 - Name: Carcinoma, Renal Cell - Relevance: HIGH - As Found: Kidney Cancer - ID: M10703 - Name: Kidney Neoplasms - Relevance: HIGH - As Found: Kidney Cancer - ID: M17320 - Name: Urologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: T4906 - Name: Renal Cell Carcinoma - Relevance: HIGH - As Found: Kidney Cancer - ID: T1341 - Name: Clear Cell Renal Cell Carcinoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007680 - Term: Kidney Neoplasms - ID: D000002292 - Term: Carcinoma, Renal Cell ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10407 - Name: Interferons - Relevance: HIGH - As Found: Recurrent - ID: M254669 - Name: Peginterferon alfa-2b - Relevance: HIGH - As Found: IDP- - ID: M19243 - Name: Interferon-alpha - Relevance: HIGH - As Found: Status - ID: M1685 - Name: Interferon alpha-2 - Relevance: HIGH - As Found: Observation - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007372 - Term: Interferons - ID: D000016898 - Term: Interferon-alpha - ID: D000077190 - Term: Interferon alpha-2 - ID: C000417083 - Term: Peginterferon alfa-2b ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03446079 **Brief Title:** Relationship of Skin Related SNP to Topical Skin Care Product **Official Title:** Relationship of Skin Related Single Nucleotide Polymorphisms to Clinical Response to a Topical Skin Care Product #### Organization Study ID Info **ID:** HCODE1 #### Organization **Class:** INDUSTRY **Full Name:** HelicalCodeMD ### Status Module #### Completion Date **Date:** 2022-12-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-01-31 **Type:** ACTUAL #### Start Date **Date:** 2018-03-19 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2018-02-26 **Type:** ACTUAL **Study First Submit Date:** 2018-02-20 **Study First Submit QC Date:** 2018-02-23 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** 23andMe, Inc. **Class:** INDUSTRY **Name:** Johnson & Johnson #### Lead Sponsor **Class:** INDUSTRY **Name:** HelicalCodeMD #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Demonstrate the relationship between single nucleotide polymorphisms (SNP) and response to a topical skin care product. **Detailed Description:** Cross sectional study will utilize gene-specific candidate and genome wide association analysis to identify SNP's that may be associated with response to a topical product. Investigators and patients will be blinded to the genetic test results, and participants will be blinded to the skin product applied. ### Conditions Module **Conditions:** - Genetics - Skin Aging **Keywords:** - Genetic - Skin - Anti Aging - SNP ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Cross sectional will utilize gene-specific candidate and genome wide association analysis to identify SNP's that may be associated with response to a topical product. ##### Masking Info **Masking:** NONE **Masking Description:** Investigators and participants will be blinded to the results genetic testing results during the trial duration. Only participants will be blinded to the identity of the study product. **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 156 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Male or female subjects 21 or older that meet the specified inclusion/exclusion criteria taking genetic test and applying topical anti aging cream per the protocol. **Intervention Names:** - Other: Topical Anti Aging Cream **Label:** Primary Subjects **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Primary Subjects **Description:** Primary Subjects will take a saliva based genetic test and apply a topical anti aging cream for 6 weeks. **Name:** Topical Anti Aging Cream **Other Names:** - Genetic Test (for association purposes only) **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The primary endpoint being studied in this study is the association of the product response to the 17 candidate SNP genotypes. **Measure:** Genetic Profile & Product Response **Time Frame:** 6 weeks #### Secondary Outcomes **Description:** The secondary endpoint will be identification of novel SNPs through genome-wide association analysis that may be associated with response to the study product. **Measure:** Novel SNP Identification **Time Frame:** 6 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. At least 21 years old in general good health as determined by a health questionnaire. 2. Willingness to cooperate and participate by following study requirements and to report any adverse symptoms immediately. 3. Willingness to discontinue the use of all facial products other than the assigned test material and their regular brands of glamour products. The glamour products must be the subject's regular brand and have been used for a minimum of one month prior to the start of the study. 4. Willingness to remove make up at least 30 minutes prior to each scheduled clinic visit. No other topical products should be applied to the face until the study visit has been completed. 5. Willingness to avoid daily direct sun exposure on the face, whether natural or at tanning salons. 6. Willingness to discontinue antiaging cosmetics including alpha hydroxyacid products (including Lachydrin©), beta hydroxyacid products (including salicylic acid), poly hydroxyacid products, retinol products, acetyl glucosamine or other effective anti-aging topical products on the face 2 weeks prior to the start of the study and throughout the duration of the study. 7. Completion and signing of a Informed Consent and Enrollment form, HIPAA form, photo release form, medical intake, skin habits survey. 8. Willingness to complete all study assessments. - Exclusion Criteria: 1. Individuals who currently or in the last month have regularly used certain topical or oral medications which, in the opinion of the Investigators, may interfere with the study or that may expose study participants to unacceptable risks. Such products include oral prescription steroids or anti-inflammatories, topical steroids, or prescription skin treatment except for mild acne, as determined by the investigators. 2. Subjects who have a history of disease or current disease or regularly use topical or oral medications which, in the opinion of the Investigator, may interfere with the study or that may expose study participants to unacceptable risks. (i.e. oral or topical steroids or anti-inflammatories, etc.). 3. Uncontrolled metabolic disease such as diabetes, hyperthyroidism, or hypothyroidism or active Hepatitis, immune deficiency, or autoimmune disease as determined by the health questionnaire. 4. Pregnancy, nursing, or planning to become pregnant during the course of the study as determined by the health questionnaire. 5. History of skin cancer within the past 6 months. 6. Use of topical prescription retinoids for anti-aging including Retin-A®, Retin-A Micro®, Renova®, Avita®, Tazorac®, or Differin® within 2 weeks prior to the start of the study. Use of oral retinoids within 6 months of the study start. 7. Subjects must not have had mid-depth or superficial chemical peel or other anti-aging procedures on the face (laser, intense pulsed light, injectable fillers microdermabrasion, etc.) within 2 months of the study start. 8. Known allergies or sensitivities to test material ingredients or any topical skin care product (i.e., alpha hydroxyacids, retinol, sunscreens, moisturizers, cleansers, masques, toners, etc.). 9. Individuals currently participating in other clinical testing. 10. Start of hormone use (including for birth control) or changed hormones less than three months prior to the start of the study. Qualified subjects must not be taking hormones or must have been taking them for at least three months prior to the study start. **Healthy Volunteers:** True **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Laguna Hills **Country:** United States **Facility:** Halcyon Dermatology **State:** California **Zip:** 92653 #### Overall Officials **Official 1:** **Affiliation:** Member **Name:** Katherine Lee, MD, MA **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04107779 **Brief Title:** Changes in Biomarkers of Cigarette Smoke Exposure After Switching Either Exclusively or Partly to JUUL ENDS **Official Title:** A Randomized, Open Label, Parallel Group Study in Adult Smokers to Evaluate Changes in Biomarkers of Cigarette Smoke Exposure After Switching Either Exclusively or Partly to Using JUUL Electronic Nicotine Delivery Systems With Two Different Nicotine Concentrations #### Organization Study ID Info **ID:** PROT-00030 #### Organization **Class:** INDUSTRY **Full Name:** Juul Labs, Inc. ### Status Module #### Completion Date **Date:** 2020-06-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-07-28 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-02-17 **Type:** ACTUAL #### Start Date **Date:** 2019-09-17 **Type:** ACTUAL **Status Verified Date:** 2020-07 #### Study First Post Date **Date:** 2019-09-27 **Type:** ACTUAL **Study First Submit Date:** 2019-09-24 **Study First Submit QC Date:** 2019-09-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Juul Labs, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A Randomized, Open Label, Parallel Group Study in Adult Smokers to Evaluate Changes in Biomarkers of Cigarette Smoke Exposure After Switching Either Exclusively or Partly to using JUUL Electronic Nicotine Delivery Systems With Two Different Nicotine Concentrations **Detailed Description:** Previous studies and data reported in the literature support that Electronic Nicotine Delivery Systems (ENDS) have less toxicant exposure. This study will serve as a clinical evaluation of exclusive-use of selected JUUL ENDS in 2 different nicotine concentrations (5%, 3%), with the purpose of gaining data to support the hypothesis that exclusive-use of JUUL ENDS over the course of 6 days will result in a significant reduction in toxicant exposure compared to combustible cigarettes. This will be a randomized, open label, parallel group study in adult smokers to be conducted at up to 5 sites in the United States. Changes in Biomarkers of Exposure (BoEs) from baseline when using four JUUL ENDS with 2 different nicotine concentrations (5%, 3%) relative to Usual Brand (UB) of combustible cigarettes and a study group abstaining from any tobacco/nicotine product use will be assessed in this study. JUUL ENDS will be used either exclusively or partially (dual-use), with subjects in the dual-use group using both JUUL 5% ENDS (choice of Virginia Tobacco (VT), Mint, Menthol or Mango flavors) and UB of combustible cigarettes. ### Conditions Module **Conditions:** - Electronic Cigarette Use - Cigarette Use, Electronic - Tobacco Use - Tobacco Smoking **Keywords:** - Electronic Nicotine Delivery System - Combustible Cigarettes - Nicotine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomized, Open-Label, Parallel-Group ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 279 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** JUUL 5% Virginia Tobacco flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 5% Virginia Tobacco ENDS **Label:** JUUL 5% Virginia Tobacco ENDS **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** JUUL 3% Virginia Tobacco flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 3% Virginia Tobacco ENDS **Label:** JUUL 3% Virginia Tobacco ENDS **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** JUUL 5% Mint flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 5% Mint ENDS **Label:** JUUL 5% Mint ENDS **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** JUUL 3% Mint flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 3% Mint ENDS **Label:** JUUL 3% Mint ENDS **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** JUUL 5% Menthol flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 5% Menthol ENDS **Label:** JUUL 5% Menthol ENDS **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** JUUL 3% Menthol flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 3% Menthol ENDS **Label:** JUUL 3% Menthol ENDS **Type:** EXPERIMENTAL #### Arm Group 7 **Description:** JUUL 5% Mango flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 5% Mango ENDS **Label:** JUUL 5% Mango ENDS **Type:** EXPERIMENTAL #### Arm Group 8 **Description:** JUUL 3% Mango flavored ENDS product \[6 days\] in confinement. **Intervention Names:** - Other: Switch from UB of Combustible Cigarette to JUUL 3% Mango ENDS **Label:** JUUL 3% Mango ENDS **Type:** EXPERIMENTAL #### Arm Group 9 **Description:** JUUL 5% Virginia Tobacco, Mint, Menthol, or Mango flavored ENDS product and usual brand of combustible cigarette \[6 days\] in confinement. **Intervention Names:** - Other: Switch to Dual-use of JUUL 5% and UB of Combustible Cigarette **Label:** Dual-use of JUUL 5% and UB of Combustible Cigarette **Type:** EXPERIMENTAL #### Arm Group 10 **Description:** Usual brand combustible cigarette \[6 days\] in confinement. **Intervention Names:** - Other: Usual Brand of cigarettes **Label:** UB of Combustible Cigarette **Type:** ACTIVE_COMPARATOR #### Arm Group 11 **Description:** Smoking abstention (no smoking) \[6 days\] in confinement. **Intervention Names:** - Other: Tobacco/Nicotine Abstention **Label:** Tobacco/Nicotine Abstention **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - JUUL 5% Virginia Tobacco ENDS **Description:** JUUL 5%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 5% Virginia Tobacco ENDS **Other Names:** - JUUL **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - JUUL 3% Virginia Tobacco ENDS **Description:** JUUL 3%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 3% Virginia Tobacco ENDS **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - JUUL 5% Mint ENDS **Description:** JUUL 5%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 5% Mint ENDS **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - JUUL 3% Mint ENDS **Description:** JUUL 3%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 3% Mint ENDS **Type:** OTHER #### Intervention 5 **Arm Group Labels:** - JUUL 5% Menthol ENDS **Description:** JUUL 5%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 5% Menthol ENDS **Type:** OTHER #### Intervention 6 **Arm Group Labels:** - JUUL 3% Menthol ENDS **Description:** JUUL 3%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 3% Menthol ENDS **Type:** OTHER #### Intervention 7 **Arm Group Labels:** - JUUL 5% Mango ENDS **Description:** JUUL 5%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 5% Mango ENDS **Type:** OTHER #### Intervention 8 **Arm Group Labels:** - JUUL 3% Mango ENDS **Description:** JUUL 3%, ENDS for 6-days in confinement **Name:** Switch from UB of Combustible Cigarette to JUUL 3% Mango ENDS **Type:** OTHER #### Intervention 9 **Arm Group Labels:** - Dual-use of JUUL 5% and UB of Combustible Cigarette **Description:** Combination use of JUUL 5% (Virginia Tobacco, Mint, Menthol or Mango flavored) and usual brand combustible cigarettes for 6-days in confinement **Name:** Switch to Dual-use of JUUL 5% and UB of Combustible Cigarette **Type:** OTHER #### Intervention 10 **Arm Group Labels:** - Tobacco/Nicotine Abstention **Description:** No smoking for 6-days in confinement. **Name:** Tobacco/Nicotine Abstention **Type:** OTHER #### Intervention 11 **Arm Group Labels:** - UB of Combustible Cigarette **Description:** Continue smoking UB for 6-days in confinement. **Name:** Usual Brand of cigarettes **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Excretion of urine total NNAL, 3-HPMA, MHBMA, and S-PMA will be assessed at baseline and following a 6-day interventional period. **Measure:** Primary biomarkers of tobacco exposure measured in urine **Time Frame:** 6 days **Description:** Exposure to carbon monoxide will be assessed through measurement of blood COHb at baseline and following a 6-day interventional period. **Measure:** Primary biomarker of tobacco exposure measured in blood **Time Frame:** 6 days #### Secondary Outcomes **Description:** Excretion of total NNN, total 1-OHP, O-toluidine, 2-NA, 4-ABP, and urine mutagenic activity will be assessed at baseline and following a 6-day interventional period. **Measure:** Secondary biomarkers of tobacco exposure measured in urine **Time Frame:** 6 days **Description:** Subjective product assessments as measured by responses to the Modified Product Evaluation Scale will be made at baseline and during the interventional period. **Measure:** Subjective product assessments as measured by the Modified Product Evaluation Scale **Time Frame:** 6 days **Description:** The degree to which subjects like the product will be assessed using the Product-Liking Questionnaire at baseline and during the interventional period. **Measure:** Product liking as measured by the Product-Liking Questionnaire visual analog scale **Time Frame:** 6 days **Description:** Urge to smoke as measured by responses to the Urge to Smoke a Cigarette Questionnaire will be assessed at baseline and during the interventional period. **Measure:** Urge to smoke as measured by the Urge to Smoke a Cigarette Questionnaire visual analog scale **Time Frame:** 6 days **Description:** Likelihood of future product use as measured by responses to the Future Intent to Use the Product Questionnaire will be made at baseline and during the interventional period. **Measure:** Likelihood of future product use as measured by the Future Intent to Use the Product Questionnaire visual analog scale **Time Frame:** 6 days **Description:** Daily consumption of the JUUL products as measured by the change in pod weight after use during the interventional period will be reported. **Measure:** Daily JUUL product consumption **Time Frame:** 6 days **Description:** Daily consumption of combustible cigarettes as measured by the number of cigarettes smoked per day at baseline and during the interventional period will be reported. **Measure:** Daily combustible cigarette consumption **Time Frame:** 6 days **Description:** Safety and tolerability will be assessed by monitoring the incidence of product-use emergent adverse events. **Measure:** Incidence of adverse events **Time Frame:** 6 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult, male or female smoker, 21 to 65 years of age, inclusive, at Screening. * Has been a smoker for at least 12 months prior to Screening. Brief periods of non-smoking (e.g., up to \~7 consecutive days due to illness, trying to quit, participation in a study where smoking was prohibited) during the 12 months prior to Screening will be permitted at the discretion of the Investigator. * Currently smokes an average of 10 or more king size or 100s manufactured combustible cigarettes per day, as reported at Screening. * Cigarettes are the only tobacco product used within (≤) 30 days prior to Screening. * Has a positive urine cotinine (≥ 200 ng/mL) at Screening. * Has an exhaled CO \> 10 ppm at Screening. * A female subject of childbearing potential must have been using 1 of the following forms of contraception and agree to continue using it through completion of the study: * hormonal (e.g., oral, vaginal ring, transdermal patch, implant, or injection) consistently for at least 3 months prior to Day -2 (Check-in); * double barrier method (e.g., condom with spermicide, diaphragm with spermicide) consistently for at least 14 days prior to Day -2 (Check-in); * intrauterine device for at least 3 months prior to Day -2 (Check-in); * a partner who has been vasectomized for at least 6 months prior to Day -2 (Check-in); * abstinence beginning at least 14 days prior to Day -2 (Check-in). * A female subject of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Day -2 (Check-in): * hysteroscopic sterilization; * bilateral tubal ligation or bilateral salpingectomy; * hysterectomy; * bilateral oophorectomy; * Or be postmenopausal with amenorrhea for at least 1 year prior to Day -2 (Check-in) and follicle-stimulating hormone (FSH) levels consistent with postmenopausal status. * Is willing to comply with the requirements of the study, including a willingness to exclusively use the JUUL products or stop smoking for the duration of the study. * Provides voluntary consent to participate in this study documented on the signed informed consent form (ICF). Exclusion Criteria: * Has a history or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. * Has a clinically significant abnormal finding on the physical examination, medical history, vital signs, ECG, or clinical laboratory results, in the opinion of the Investigator. * Has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV). * Has had an acute illness (e.g., upper respiratory infection, viral infection) requiring treatment (including over-the-counter (OTC) remedies) within 14 days prior to Day -2 (Check-in). * Has a fever (\> 100.5°F) at Screening or Day -2 (Check-in). * Has used prescription or OTC bronchodilator medication (e.g. inhaled or oral βadrenergic agonists) to treat a chronic condition within the 12 months prior to admission; * Currently has or recently had a bladder or urinary tract infection within 30 days prior to Check-In (Day -2). * Has a body mass index (BMI) \> 40 kg/m2 or \< 18 kg/m2 at Screening. * Has a history of drug or alcohol abuse within 24 months prior to Day -2 (Check-in), as determined by the Investigator * Has diabetes mellitus, asthma, or chronic obstructive pulmonary disease (COPD). * Has a systolic blood pressure \< 90 mmHg or \> 150 mmHg, diastolic blood pressure \< 40 mmHg or \> 95 mmHg, or heart rate \< 40 bpm or \> 99 bpm at Screening. * Has a post-bronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio \< 0.7 and FEV1 \< 80% of predicted at Screening. * Has a post-bronchodilator FEV1 increase \> 12% and \> 200 mL from pre- to post-bronchodilator at Screening. * Has experienced an allergic reaction following previous e-cigarette use or with exposure to any primary components of the JUUL liquids (benzoic acid, propylene glycol and glycerol). * Has an estimated creatinine clearance \< 70 mL/minute (using the Cockcroft-Gault equation) at Screening. * Has a positive urine screen for drugs of abuse or positive urine/breath screen for alcohol at Screening or Day -2 (Check-in). * If female, the subject is pregnant, lactating, or intends to become pregnant during the time period from Screening through the end of study. * Has used medications known to interact with cytochrome P450 (CYP) 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to Day -2 (Check-in). * Has used nicotine-containing products other than manufactured cigarettes (e.g., ENDS, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, hookah/shisha, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) within 30 days prior to Day -2 (Check-in), except as required per protocol (e.g., the brief product trial at Screening). * Has a prior history of JUUL product use within (≤) 30 days prior to Screening. * Has used any prescription smoking cessation treatments, including, but not limited to, varenicline (Chantix®) or buproprion (Zyban®) within 3 months prior to Day -2 (Check-in). * Is a self-reported puffer (i.e., adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale). * Is planning to quit smoking during the study or within 3 months following Day 1, or is postponing a quit attempt in order to participate in the study. * Negative response (i.e., unwilling to use or unable to tolerate \[e.g., experiences Adverse Events during the product trial that will prevent the subjects from continuing to use the JUUL product as judged by the Investigator\]) to any of the JUUL products at Screening. * Has donated plasma within 7 days prior to Day -2 (Check-in). * Has donated blood or blood products (with the exception of plasma as noted above), has had significant blood loss, or received whole blood or a blood product transfusion within 3 months prior to Day -2 (Check-in). * Has taken any multivitamin, fish oil or biotin supplements within 48 hours prior to Check-in (Day -2). * Has consumed any cured meats (e.g., bacon, ham, sausage, corned beef, jerky) or meats cooked at high temperatures (e.g., grilled, fried, smoked or barbecued) within 2 days prior to Check-in (Day -2). * Has consumed any grapefruit (including grapefruit juice) eggplant or cruciferous vegetables (e.g., cauliflower, cabbage, kale, garden cress, bok choy, broccoli, brussels sprouts and similar green leaf vegetables) within 48 hours prior to Check-in (Day -2). * Has participated in a previous clinical study for an investigational drug, device, biologic, or tobacco product within 30 days prior to Day -2 (Check-in). * Is or has a first-degree relative (i.e., parent, sibling, child) who is a current employee of any of the study sites. * Is or has a first-degree relative (i.e., parent, sibling, child) who is a current employee, shareholder, or is member of the board of directors of JUUL Labs Inc. * Has previously taken part in, been withdrawn from, or has completed this study. * Has previously been diagnosed with any form of cancer, except for basal cell or squamous epithelial carcinomas of the skin that have been resected at least 1 year prior to Screening. * In the opinion of the Investigator, the subject should not participate in this study. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Little Rock **Country:** United States **Facility:** Woodland International Research Group **State:** Arkansas **Zip:** 72211 **Location 2:** **City:** Rogers **Country:** United States **Facility:** Woodland Research Northwest **State:** Arkansas **Zip:** 72758 **Location 3:** **City:** Saint Louis **Country:** United States **Facility:** St. Louis Clinical Trials **State:** Missouri **Zip:** 63141 **Location 4:** **City:** Dayton **Country:** United States **Facility:** Midwest Clinical Research Center **State:** Ohio **Zip:** 45417 **Location 5:** **City:** San Antonio **Country:** United States **Facility:** Endeavor Clinical Trials **State:** Texas **Zip:** 78229 #### Overall Officials **Official 1:** **Affiliation:** Juul Labs, Inc. **Name:** Mark Rubinstein, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Wang TW, Asman K, Gentzke AS, Cullen KA, Holder-Hayes E, Reyes-Guzman C, Jamal A, Neff L, King BA. Tobacco Product Use Among Adults - United States, 2017. MMWR Morb Mortal Wkly Rep. 2018 Nov 9;67(44):1225-1232. doi: 10.15585/mmwr.mm6744a2. **PMID:** 30408019 **Citation:** U. S. Department of Health and Human Services. The health consequences of smoking - 50 years of progress: A report of the Surgeon General. Department of Health and Human Services, Public Health Service, Office of the Surgeon General. U. S. Government Printing Office, Washington, D. C. (2014) **Citation:** Babb S, Malarcher A, Schauer G, Asman K, Jamal A. Quitting Smoking Among Adults - United States, 2000-2015. MMWR Morb Mortal Wkly Rep. 2017 Jan 6;65(52):1457-1464. doi: 10.15585/mmwr.mm6552a1. **PMID:** 28056007 **Citation:** Gottlieb S, Zeller M. A Nicotine-Focused Framework for Public Health. N Engl J Med. 2017 Sep 21;377(12):1111-1114. doi: 10.1056/NEJMp1707409. Epub 2017 Aug 16. No abstract available. **PMID:** 28813211 **Citation:** Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. doi: 10.1056/NEJMc1413069. No abstract available. **PMID:** 25607446 **Citation:** D'Ruiz CD, Graff DW, Robinson E. Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes. BMC Public Health. 2016 Jul 11;16:543. doi: 10.1186/s12889-016-3236-1. **PMID:** 27401980 **Citation:** McNeill A et al. E-cigarettes: An Evidence Update. A report commissioned by Public Health England. Available at: https://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/457102/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf (Aug 2015). **Citation:** Polosa R, Morjaria J, Caponnetto P, Caruso M, Strano S, Battaglia E, Russo C. Effect of smoking abstinence and reduction in asthmatic smokers switching to electronic cigarettes: evidence for harm reversal. Int J Environ Res Public Health. 2014 May 8;11(5):4965-77. doi: 10.3390/ijerph110504965. **PMID:** 24814944 **Citation:** Tanner JA, Tyndale RF. Variation in CYP2A6 Activity and Personalized Medicine. J Pers Med. 2017 Dec 1;7(4):18. doi: 10.3390/jpm7040018. **PMID:** 29194389 **Citation:** HIPAA Privacy Rule. Information for Researchers. De-identifying Protected Health Information Under the Privacy Rule. U.S. Department of Health and Human Services. NIH (Feb 2007). Available at: http://privacyruleandresearch.nih.gov/pr_08.asp#8a. **Citation:** Fagerstrom K. Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence. Nicotine Tob Res. 2012 Jan;14(1):75-8. doi: 10.1093/ntr/ntr137. Epub 2011 Oct 24. No abstract available. **PMID:** 22025545 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000005731 - Term: Ganglionic Stimulants - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018722 - Term: Nicotinic Agonists - ID: D000018679 - Term: Cholinergic Agonists - ID: D000018678 - Term: Cholinergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000982 - Term: Antipruritics - ID: D000003879 - Term: Dermatologic Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: CNSSti - Name: Central Nervous System Stimulants - Abbrev: HB - Name: Herbal and Botanical ### Intervention Browse Module - Browse Leaves - ID: M12478 - Name: Nicotine - Relevance: HIGH - As Found: Prior to - ID: M11591 - Name: Menthol - Relevance: HIGH - As Found: Window - ID: M4029 - Name: Central Nervous System Stimulants - Relevance: LOW - As Found: Unknown - ID: M20796 - Name: Nicotinic Agonists - Relevance: LOW - As Found: Unknown - ID: M20758 - Name: Cholinergic Agents - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M7074 - Name: Dermatologic Agents - Relevance: LOW - As Found: Unknown - ID: T221 - Name: Mango - Relevance: HIGH - As Found: INH ### Intervention Browse Module - Meshes - ID: D000008610 - Term: Menthol - ID: D000009538 - Term: Nicotine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04109079 **Acronym:** ATNEC **Brief Title:** Axillary Management in Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy **Official Title:** ATNEC - Axillary Management in T1-3N1M0 Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases at Presentation After Neoadjuvant Chemotherapy #### Organization Study ID Info **ID:** NIHR 128311 #### Organization **Class:** OTHER **Full Name:** University Hospitals of Derby and Burton NHS Foundation Trust ### Status Module #### Completion Date **Date:** 2030-02-28 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-31 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-30 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2030-02-28 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-26 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2019-09-30 **Type:** ACTUAL **Study First Submit Date:** 2019-09-27 **Study First Submit QC Date:** 2019-09-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospitals of Derby and Burton NHS Foundation Trust #### Responsible Party **Investigator Affiliation:** University Hospitals of Derby and Burton NHS Foundation Trust **Investigator Full Name:** Dr Amit Goyal **Investigator Title:** Consultant Oncoplastic Breast Surgeon & Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of this study is to assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years. **Detailed Description:** Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease. Aim: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years. Methods: Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio. Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node). Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years. Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years. Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness. Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years. Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated. Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination. ### Conditions Module **Conditions:** - Breast Cancer - Sentinel Lymph Node - Neoplasm, Breast **Keywords:** - neoadjuvant chemotherapy - sentinel node biopsy - breast cancer - tattooing node - marking node - clip node - axillary ultrasound - node positive - axillary lymph node dissection - axillary radiotherapy - axillary treatment ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1900 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in this arm will not receive axillary treatment (axillary lymph node dissection or axillary radiotherapy). Supraclavicular fossa radiotherapy is not allowed when randomised to this arm. **Intervention Names:** - Radiation: Breast or chest wall radiotherapy **Label:** No axillary treatment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients in this arm will receive axillary treatment. Axillary treatment can be axillary lymph node dissection or axillary radiotherapy. **Intervention Names:** - Procedure: Axillary lymph node dissection - Radiation: Axillary radiotherapy - Radiation: Breast or chest wall radiotherapy **Label:** Axillary treatment **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Axillary treatment **Description:** Participants will undergo removal of at least level I and II axillary lymph nodes. **Name:** Axillary lymph node dissection **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Axillary treatment **Description:** Axillary radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines. **Name:** Axillary radiotherapy **Type:** RADIATION #### Intervention 3 **Arm Group Labels:** - Axillary treatment - No axillary treatment **Description:** Breast or chest wall radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines. **Name:** Breast or chest wall radiotherapy **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** DFS calculated as the time from randomisation until the date of first event of either a loco-regional invasive breast cancer relapse, distant relapse, ipsilateral or contralateral new invasive primary breast cancer or death by any cause or the censor date. **Measure:** Disease free survival (DFS) **Time Frame:** 5 years **Description:** Lymphoedema is self-reported based on two items from the validated Lymphoedema and Breast Cancer Questionnaire (arm "swelling now" and arm "heaviness in the past year"). Lymphoedema is defined as 'yes' to both questions. **Measure:** Patient reported lymphoedema **Time Frame:** 5 years #### Secondary Outcomes **Description:** Arm function will be assessed using shortened version of the Disability of the Arm, Shoulder and Hand (DASH), the 11-item QuickDASH questionnaire. Physical disability is defined as a change from baseline in the QuickDASH score of at least 14 points. **Measure:** Arm function **Time Frame:** 5 years **Description:** Health related quality of life will be assessed with EQ-5D-5L **Measure:** Health related quality of life: EQ-5D-5L **Time Frame:** 5 years **Description:** Axillary recurrence free interval, calculated from the date of randomisation to the date of axillary recurrence or the censor date. **Measure:** Axillary recurrence free interval **Time Frame:** 5 years **Description:** Overall survival calculated as the time from randomisation until the date of death by any cause or the censor date. **Measure:** Overall survival **Time Frame:** 5 years **Description:** Number of participants with local (breast or chest wall) recurrence **Measure:** Local (breast or chest wall) recurrence **Time Frame:** 5 years **Description:** Number of participants with regional (nodal) recurrence **Measure:** Regional (nodal) recurrence **Time Frame:** 5 years **Description:** Number of participants with distant metastasis. **Measure:** Distant metastasis **Time Frame:** 5 years **Description:** Number of participants with contralateral breast cancer. **Measure:** Contralateral breast cancer **Time Frame:** 5 years **Description:** Number of participants with non-breast cancer **Measure:** Non-breast cancer **Time Frame:** 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * cT1-3N1M0 breast cancer at diagnosis (prior to NACT) by American Joint Committee on Cancer (AJCC) staging 8th edition * Patients with occult primary breast cancer (no identifiable invasive cancer in the breast) with FNA or core biopsy proven nodal metastases are also eligible for the study. * Fine-needle aspiration (FNA) or core biopsy confirmed axillary nodal metastases at presentation * Oestrogen receptor and HER2 status evaluated on primary tumour * Received standard NACT as per local guidelines (Patients undergoing neoadjuvant endocrine therapy as part of another clinical trial are eligible) * Imaging of the axilla, as required, to assess response to NACT (per local guidelines) * Undergo a dual tracer sentinel node biopsy (SNB) after NACT with at least 3 nodes removed in total (sentinel nodes and marked node). * If a single tracer SNB is performed, the patient is eligible only if the involved node is marked before or during NACT, and at least 3 nodes (including the marked node) are removed during sentinel node biopsy. * If the node is not marked, or the marked node is not removed, the patient is eligible only if the histology report shows evidence of down-staging with complete pathological response e.g. fibrosis or scarring in at least one node and at least 3 nodes removed. * If fewer than 3 nodes are found on histology, the patient is eligible only if BOTH points a) and b) below, are met: 1. involved node was marked and removed during SNB; and 2. removed marked node shows evidence of downstaging on histology e.g. fibrosis or scarring. * If the sentinel node(s) cannot be localised on SNB: axillary node sampling should be performed, the patient will be eligible if at least 3 nodes are removed (including the marked node). * No evidence of nodal metastases post NACT (isolated tumour cells, micro or macro metastasis) * Patients with complete pathological response in the axilla but residual disease in the breast post NACT are eligible for the study. Exclusion Criteria: * Bilateral synchronous invasive breast cancer * Sentinel node biopsy prior to NACT * Previous axillary surgery on the same body side as the scheduled targeted sampling * Any previous cancer within 5 years or concomitant malignancy except * basal or squamous cell carcinoma of the skin * in situ carcinoma of the cervix * in situ melanoma * contra- or ipsilateral in situ breast cancer **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** amit.goyal@nhs.net **Name:** Amit Goyal, MS, MD, FRCS **Phone:** +44 1332785538 **Role:** CONTACT #### Locations **Location 1:** **City:** Keighley **Contacts:** ***Contact 1:*** - **Name:** Claire Murphy - **Role:** CONTACT **Country:** United Kingdom **Facility:** Airedale NHS Foundation Trust **State:** Bd20 6td **Status:** RECRUITING **Location 2:** **City:** Carlisle **Contacts:** ***Contact 1:*** - **Name:** Ludger Barthelmes - **Role:** CONTACT **Country:** United Kingdom **Facility:** North Cumbria Integrated Care NHS Foundation Trust **State:** Ca2 7hy **Status:** RECRUITING **Location 3:** **City:** Camberley **Contacts:** ***Contact 1:*** - **Name:** Kaiyumars Contractor - **Role:** CONTACT ***Contact 2:*** - **Name:** Hisham Osman - **Role:** CONTACT **Country:** United Kingdom **Facility:** Frimley Health NHS Foundation Trust **State:** Gu16 7uj **Status:** RECRUITING **Location 4:** **City:** Inverness **Contacts:** ***Contact 1:*** - **Name:** Eileen Anderson - **Role:** CONTACT **Country:** United Kingdom **Facility:** NHS Highland **State:** Iv2 3uj **Status:** RECRUITING **Location 5:** **City:** Great Yarmouth **Contacts:** ***Contact 1:*** - **Name:** Sue Down - **Role:** CONTACT **Country:** United Kingdom **Facility:** James Paget University Hospitals NHS Foundation Trust **State:** Nr31 6la **Status:** RECRUITING **Location 6:** **City:** Reading **Contacts:** ***Contact 1:*** - **Name:** Brendan Smith - **Role:** CONTACT **Country:** United Kingdom **Facility:** Royal Berkshire NHS Foundation Trust **State:** Rg1 5an **Status:** RECRUITING **Location 7:** **City:** Macclesfield **Contacts:** ***Contact 1:*** - **Name:** Jalal Kokan - **Role:** CONTACT **Country:** United Kingdom **Facility:** East Cheshire NHS Trust **State:** Sk10 3bl. **Status:** RECRUITING **Location 8:** **City:** Shrewsbury **Contacts:** ***Contact 1:*** - **Name:** Laura Pettit - **Role:** CONTACT **Country:** United Kingdom **Facility:** The Shrewsbury and Telford Hospitals NHS Trust **State:** Sy3 8xq **Status:** RECRUITING **Location 9:** **City:** Aberdeen **Contacts:** ***Contact 1:*** - **Name:** Beatrix Elsberger - **Role:** CONTACT **Country:** United Kingdom **Facility:** NHS Grampian **Status:** RECRUITING **Zip:** AB25 2ZN **Location 10:** **City:** Ashford **Contacts:** ***Contact 1:*** - **Name:** Anneliese Lawn - **Role:** CONTACT **Country:** United Kingdom **Facility:** Ashford and St Peter's Hospitals NHS Foundation Trust **Status:** RECRUITING **Zip:** TW15 3AA **Location 11:** **City:** Ashton-under-Lyne **Contacts:** ***Contact 1:*** - 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**Name:** Brinda Sethugavalar - **Role:** CONTACT **Country:** United Kingdom **Facility:** South Tees Hospitals NHS Foundation Trust **Status:** RECRUITING **Zip:** TS4 3BW **Location 57:** **City:** Milton Keynes **Contacts:** ***Contact 1:*** - **Name:** Amanda Taylor - **Role:** CONTACT **Country:** United Kingdom **Facility:** Milton Keynes University Hospital NHS Trust **Status:** RECRUITING **Zip:** MK6 5LD **Location 58:** **City:** Newcastle Upon Tyne **Contacts:** ***Contact 1:*** - **Name:** Henry Cain - **Role:** CONTACT **Country:** United Kingdom **Facility:** Newcastle Upon Tyne Hospitals NHS Foundation Trust **Status:** RECRUITING **Zip:** NE1 4LP **Location 59:** **City:** Oxford **Contacts:** ***Contact 1:*** - **Name:** Pankaj Roy - **Role:** CONTACT **Country:** United Kingdom **Facility:** Oxford University Hospitals NHS Foundation Trust **Status:** RECRUITING **Zip:** OX3 7LE **Location 60:** **City:** Paisley **Contacts:** ***Contact 1:*** - **Name:** Abdulla Alhasso - **Role:** CONTACT **Country:** United Kingdom **Facility:** NHS Greater Glasgow and Clyde **Status:** RECRUITING **Zip:** PA2 9PN **Location 61:** **City:** Plymouth **Contacts:** ***Contact 1:*** - **Name:** Saed Ramzi - **Role:** CONTACT **Country:** United Kingdom **Facility:** University Hospitals Plymouth NHS Trust **Status:** RECRUITING **Zip:** PL6 8DH **Location 62:** **City:** Prescot **Contacts:** ***Contact 1:*** - **Name:** Tamara Kiernan - **Role:** CONTACT **Country:** United Kingdom **Facility:** St Helens and Knowsley Teaching Hospitals NHS Trust **Status:** RECRUITING **Zip:** L35 5DR **Location 63:** **City:** Rotherham **Contacts:** ***Contact 1:*** - **Name:** Tahir Masudi - **Role:** CONTACT **Country:** United Kingdom **Facility:** The Rotherham NHS Foundation Trust **Status:** RECRUITING **Zip:** S60 2UD **Location 64:** **City:** St Albans **Contacts:** ***Contact 1:*** - **Name:** Lee Min Lai - **Role:** CONTACT **Country:** United Kingdom **Facility:** West Hertfordshire Hospitals NHS Trust **Status:** RECRUITING **Zip:** AL3 5PN **Location 65:** **City:** Stevenage **Contacts:** ***Contact 1:*** - **Name:** Muhammed Baki - **Role:** CONTACT **Country:** United Kingdom **Facility:** East and North Hertfordshire NHS Foundation Trust **Status:** RECRUITING **Zip:** SG1 4AB **Location 66:** **City:** Stockton-on-Tees **Contacts:** ***Contact 1:*** - **Name:** Matei Dordea - **Role:** CONTACT **Country:** United Kingdom **Facility:** North Tees and Hartlepool NHS Foundation Trust **Status:** RECRUITING **Zip:** TS19 8PE **Location 67:** **City:** Stoke-on-Trent **Contacts:** ***Contact 1:*** - **Name:** Sekhar Marla - **Role:** CONTACT **Country:** United Kingdom **Facility:** University Hospitals of North Midlands NHS Trust **Status:** RECRUITING **Zip:** ST4 6QG **Location 68:** **City:** Taunton **Contacts:** ***Contact 1:*** - **Name:** Zoe Goldthorpe - **Role:** CONTACT **Country:** United Kingdom **Facility:** Somerset NHS Foundation Trust **Status:** RECRUITING **Zip:** TA1 5DA **Location 69:** **City:** Thornton Heath **Contacts:** ***Contact 1:*** - **Name:** Lubna Noor - **Role:** CONTACT **Country:** United Kingdom **Facility:** Croydon Health Services NHS Trust **Status:** RECRUITING **Zip:** CR7 7YE **Location 70:** **City:** Truro **Contacts:** ***Contact 1:*** - **Name:** Duncan Wheatley - **Role:** CONTACT **Country:** United Kingdom **Facility:** Royal Cornwall Hospitals NHS Trust **Status:** RECRUITING **Zip:** TR1 3LJ **Location 71:** **City:** Wakefield **Contacts:** ***Contact 1:*** - **Name:** Daniel Glassman - **Role:** CONTACT **Country:** United Kingdom **Facility:** Mid Yorkshire Hospitals NHS Trust **Status:** RECRUITING **Zip:** WF1 4DG **Location 72:** **City:** Westcliff-on-Sea **Contacts:** ***Contact 1:*** - **Name:** Abdul Syed - **Role:** CONTACT **Country:** United Kingdom **Facility:** Mid and South Essex NHS Foundation Trust **Status:** RECRUITING **Zip:** SS0 0RY **Location 73:** **City:** Wigan **Contacts:** ***Contact 1:*** - **Name:** Konstantinos Zacharioudakis - **Role:** CONTACT **Country:** United Kingdom **Facility:** Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust **Status:** RECRUITING **Zip:** WN1 2NN **Location 74:** **City:** Wirral **Contacts:** ***Contact 1:*** - **Name:** Shaveta Mehta - **Role:** CONTACT **Country:** United Kingdom **Facility:** Clatterbridge Cancer Centre NHS Foundation Trust **Status:** RECRUITING **Zip:** CH63 4JY **Location 75:** **City:** Wirral **Contacts:** ***Contact 1:*** - **Name:** Raman Vinayagam - **Role:** CONTACT **Country:** United Kingdom **Facility:** Wirral University Teaching Hospital NHS Foundation Trust **Status:** RECRUITING **Zip:** CH63 4JY **Location 76:** **City:** Wolverhampton **Contacts:** ***Contact 1:*** - **Name:** Raghavan Vidya - **Role:** CONTACT **Country:** United Kingdom **Facility:** The Royal Wolverhampton NHS Trust **Status:** RECRUITING **Zip:** WV10 0QP **Location 77:** **City:** Yeovil **Contacts:** ***Contact 1:*** - **Name:** Caroline Osborne - **Role:** CONTACT **Country:** United Kingdom **Facility:** Yeovil District Hospital NHS Trust **Status:** RECRUITING **Zip:** BA21 4AT **Location 78:** **City:** York **Contacts:** ***Contact 1:*** - **Name:** Bhavani Rengabashyam - **Role:** CONTACT **Country:** United Kingdom **Facility:** York and Scarborough Teaching Hospitals NHS Foundation Trust **Status:** RECRUITING **Zip:** YO31 8HE #### Overall Officials **Official 1:** **Affiliation:** Royal Derby Hospital, Derby, UK **Name:** Amit Goyal, MS, MD, FRCS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### See Also Links **Label:** Training video for surgeons to remove the marked node during sentinel node biopsy **URL:** https://youtu.be/SFAzvkpkM84 **Label:** Training video for radiologists to mark the node using black dye tattoo **URL:** https://youtu.be/Nq3tmI6l66s **Label:** Training video for radiologists to mark the node using clip **URL:** https://youtu.be/nLA0fYihVOc **Label:** ATNEC breast cancer study - Research Nurse and Patient Consultation **URL:** https://www.youtube.com/watch?v=s5vqST08HYE **Label:** ATNEC breast cancer study - Example Doctor and Patient Consultation **URL:** https://www.youtube.com/watch?v=0zAl4PkJV-w&t=4s ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02799979 **Acronym:** HTP3S **Brief Title:** 3D Imaging: Prognostic Role in Pulmonary Arterial Hypertension **Official Title:** 3D Imaging: Prognostic Role in Pulmonary Arterial Hypertension #### Organization Study ID Info **ID:** 14-AOI-08 #### Organization **Class:** OTHER **Full Name:** Centre Hospitalier Universitaire de Nice ### Status Module #### Completion Date **Date:** 2019-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2017-10-05 **Type:** ACTUAL **Last Update Submit Date:** 2017-10-03 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-10 **Type:** ESTIMATED #### Start Date **Date:** 2014-10 **Status Verified Date:** 2017-10 #### Study First Post Date **Date:** 2016-06-15 **Type:** ESTIMATED **Study First Submit Date:** 2016-05-30 **Study First Submit QC Date:** 2016-06-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre Hospitalier Universitaire de Nice #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Pulmonary hypertension is a rare and severe disease, affecting a young population. Survival is very poor and has been closely related to right ventricular dysfunction. Current prognostic equations rely mostly on right heart catheterization data. The identification of simple echocardiographic prognostic factor is urgently needed. It could help identifying with a non invasive method, high risk patients who could benefit from an intensive specific therapy. 3D right ventricular imaging is a new echocardiographic tool which provides RV volumic analysis, RV ejection fraction, overcoming the classical limits of 2D ultrasound. The aim of this study is to validate a new software for 3D analysis of the right ventricle and assess its prognostic role in pulmonary hypertension. To do so, the investigators will realize a prospective monocentric longitudinal cohort study, including 100 pulmonary hypertension patients. Echocardiographic data will be collected at baseline and after 6 months. ### Conditions Module **Conditions:** - Pulmonary Arterial Hypertension ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 150 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Echocardiographic data : 3D right ventricular imaging on 100 pulmonary hypertension patients at Baseline and after six months **Intervention Names:** - Device: 3D right ventricular imaging echocardiographic **Label:** Case #### Arm Group 2 **Description:** Echocardiographic data : 3D right ventricular Imaging on 50 patients without pulmonary hypertension only at baseline **Intervention Names:** - Device: 3D right ventricular imaging echocardiographic **Label:** Control ### Interventions #### Intervention 1 **Arm Group Labels:** - Case - Control **Description:** Echocardiographic data (3D right ventricular imaging echocardiographic) will be collected at baseline and after 6months. **Name:** 3D right ventricular imaging echocardiographic **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Description of the number of death during the study **Measure:** Number of death from any cause **Time Frame:** Baseline to 24 months #### Secondary Outcomes **Description:** Description of the number of hospitalisation for worsening of pulmonary arterial hypertension **Measure:** Number of Hospitalisation **Time Frame:** Baseline to 24 months **Description:** Analyse the data of 3D right ventricular (RV), ejection fraction, RV telediastolic and telesystolic volume, 3D RV area strain (%) **Measure:** 3D right ventricular imaging echocardiographic **Time Frame:** Baseline and 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients \> 18 years old * Pulmonary hypertension diagnosed by right heart catheterization * Informed consent obtained * Affiliation to the French national health insurance Exclusion Criteria: * Associated significant left heart disease * Sub-optimal acoustic windows * Patient unable to attend follow-up visits **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with pulmonary hypertension diagnosed ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** moceri.p@chu-nice.fr **Name:** PAMELA MOCERI, MD **Phone:** 4 92 03 77 34 **Phone Ext:** +33 **Role:** CONTACT #### Locations **Location 1:** **City:** Nice **Contacts:** ***Contact 1:*** - **Email:** moceri.p@chu-nice.fr - **Name:** PAMELA MOCERI, MD - **Phone:** 4 92 03 77 34 - **Phone Ext:** +33 - **Role:** CONTACT **Country:** France **Facility:** Hopital Pasteur - Chu Nice **Status:** RECRUITING **Zip:** 06000 #### Overall Officials **Official 1:** **Affiliation:** CHU NICE **Name:** PAMELA MOCERI, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** YES ### References Module #### References **Citation:** Moceri P, Duchateau N, Baudouy D, Squara F, Bun SS, Ferrari E, Sermesant M. Additional prognostic value of echocardiographic follow-up in pulmonary hypertension-role of 3D right ventricular area strain. Eur Heart J Cardiovasc Imaging. 2022 Oct 20;23(11):1562-1572. doi: 10.1093/ehjci/jeab240. **PMID:** 36265185 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006976 - Term: Hypertension, Pulmonary - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M2261 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - ID: M10027 - Name: Hypertension, Pulmonary - Relevance: LOW - As Found: Unknown - ID: M30541 - Name: Familial Primary Pulmonary Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T4807 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension ### Condition Browse Module - Meshes - ID: D000081029 - Term: Pulmonary Arterial Hypertension - ID: D000065627 - Term: Familial Primary Pulmonary Hypertension - ID: D000006973 - Term: Hypertension ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00596479 **Brief Title:** Filgrastim for the Promotion of Collateral Growth in Patients With CAD **Official Title:** Subcutaneous Delivery of Filgrastim (rG-CSF) for the Promotion of Collateral Growth in Patients With Coronary Artery Disease #### Organization Study ID Info **ID:** 05/04 #### Organization **Class:** OTHER **Full Name:** Insel Gruppe AG, University Hospital Bern ### Status Module #### Completion Date **Date:** 2007-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-06-16 **Type:** ESTIMATED **Last Update Submit Date:** 2015-06-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-12 **Type:** ACTUAL #### Start Date **Date:** 2004-11 **Status Verified Date:** 2015-06 #### Study First Post Date **Date:** 2008-01-17 **Type:** ESTIMATED **Study First Submit Date:** 2008-01-08 **Study First Submit QC Date:** 2008-01-16 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Swiss National Science Foundation **Class:** OTHER **Name:** Swiss Heart Foundation #### Lead Sponsor **Class:** OTHER **Name:** Insel Gruppe AG, University Hospital Bern #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** The purpose of this study in humans with stable coronary artery disease (CAD) treatable by PCI (percutaneous coronary intervention) is to evaluate the safety and efficacy of subcutaneous delivery of recombinant granulocyte colony stimulating factor rG-CSF (Filgrastim, Neupogen®, Amgen Switzerland) with regard to the promotion of collateral growth. **Detailed Description:** The purpose of this study in humans with stable coronary artery disease (CAD) treatable by PCI (percutaneous coronary intervention) is to evaluate the safety and efficacy of subcutaneous delivery of recombinant granulocyte colony stimulating factor rG-CSF (Filgrastim, Neupogen®, Amgen Switzerland) with regard to the promotion of collateral growth. ### Conditions Module **Conditions:** - Coronary Artery Disease **Keywords:** - CAD - G-CSF - Collaterals - CFI - perfusion ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Filgrastim (rG-CSF) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Collateral flow index (CFI) at 2 weeks follow-up compared to baseline CFI #### Secondary Outcomes **Measure:** Absolute myocardial perfusion during hyperemia by contrast echocardiography (MCE) at baseline, at 2 weeks and at 6 month follow-up ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \> 18 years old * 1- to 3-vessel coronary artery disease (CAD) * Stable angina pectoris * At least 1 stenotic lesion suitable for PCI * No Q-wave myocardial infarction in the area undergoing CFI measurement * Written informed consent to participate in the study Exclusion Criteria: * Patients admitted as emergencies * Acute myocardial infarction * Unstable CAD * CAD treated best by CABG * Patients with overt neoplastic disease * Patients with diabetic retinopathy * Liver or kidney disease * Pre-menopausal women **Maximum Age:** 90 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bern **Country:** Switzerland **Facility:** University Hospital Bern **Zip:** 3010 #### Overall Officials **Official 1:** **Affiliation:** University of Bern **Name:** Steffen Gloekler, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Bern **Name:** Tobias Rutz, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** University of Bern **Name:** Pascal Meier, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 4:** **Affiliation:** University of Bern **Name:** Christian Seiler, MD **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Meier P, Gloekler S, de Marchi SF, Indermuehle A, Rutz T, Traupe T, Steck H, Vogel R, Seiler C. Myocardial salvage through coronary collateral growth by granulocyte colony-stimulating factor in chronic coronary artery disease: a controlled randomized trial. Circulation. 2009 Oct 6;120(14):1355-63. doi: 10.1161/CIRCULATIONAHA.109.866269. Epub 2009 Sep 21. **PMID:** 19770393 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6549 - Name: Coronary Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M19506 - Name: Myocardial Ischemia - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003324 - Term: Coronary Artery Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000003327 - Term: Coronary Disease ### Intervention Browse Module - Ancestors - ID: D000000276 - Term: Adjuvants, Immunologic - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1945 - Name: Lenograstim - Relevance: HIGH - As Found: 30 minutes - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000078224 - Term: Lenograstim ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04172779 **Brief Title:** Erlotinib for Hepatocellular Carcinoma Chemoprevention **Official Title:** Phase IIa Single-arm Clinical Trial of Hepatocellular Carcinoma Chemoprevention With Low-dose Erlotinib in Patients With Liver Cirrhosis #### Organization Study ID Info **ID:** STU-2019-1515 #### Organization **Class:** OTHER **Full Name:** University of Texas Southwestern Medical Center ### Status Module #### Completion Date **Date:** 2029-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-01 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-29 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2029-06 **Type:** ESTIMATED #### Start Date **Date:** 2024-07 **Type:** ESTIMATED **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2019-11-21 **Type:** ACTUAL **Study First Submit Date:** 2019-11-17 **Study First Submit QC Date:** 2019-11-19 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** University of Texas Southwestern Medical Center #### Responsible Party **Investigator Affiliation:** University of Texas Southwestern Medical Center **Investigator Full Name:** Yujin Hoshida, MD, PhD **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This phase IIa trial studies long-term low-dose erlotinib hydrochloride treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with liver cirrhosis. ### Conditions Module **Conditions:** - Cirrhosis, Liver **Keywords:** - hepatocellular carcinoma - chemoprevention ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Erlotinib Hydrochloride **Label:** Erlotinib treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Erlotinib treatment **Description:** Oral administration of erlotinib 25mg tablet **Name:** Erlotinib Hydrochloride **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** The relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using analysis of variance (ANOVA) or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests. **Measure:** Changes in phospho-ERK levels in the liver **Time Frame:** Baseline to week 48 **Description:** The relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests. **Measure:** Changes in PCNA levels in the liver **Time Frame:** Baseline to week 48 **Description:** The relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests. **Measure:** Changes in EGF levels in the liver **Time Frame:** Baseline to week 48 **Description:** The relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests. **Measure:** Changes in alphaSMA levels in the liver **Time Frame:** Baseline to week 48 **Description:** The relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests. **Measure:** Changes in GSTp levels in the liver **Time Frame:** Baseline to week 48 #### Primary Outcomes **Description:** The relationship between the treatment and modulation of a gene expression signature associated with HCC risk will be assessed. Expression levels of the signature genes will be compared between baseline and at the end of treatment, and magnitude of the modulation will be measured by Kolmogorov-Smirnov statistic-based Combined Enrichment Score (CES) and tested for significance by using one-sample t-test. **Measure:** Modulation of gene expression signatures associated with hepatocellular carcinoma (HCC) risk **Time Frame:** Baseline to week 48 #### Secondary Outcomes **Description:** Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately. Overall toxicity incidence, as well as toxicity profiles will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. **Measure:** Overall adverse event profile for erlotinib hydrochloride **Time Frame:** Baseline to week 48 **Description:** QOL will be measured by using the SF-12v2 health survey questionnaire, and compared between baseline and end of the treatment. Frequency distributions, graphical techniques and other descriptive measures will be used to summarize the results. Paired t-test will be used to assess change of the measurements. **Measure:** Change in quality of life (QOL) **Time Frame:** Baseline to week 48 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults (≥ 18 years-old) * Clinically and/or histologically diagnosed cirrhosis * No active hepatic decompensation * No prior history of HCC * Adequate hematologic, hepatic, and renal function, Karnofsky performance status score ≥70 * Both sexes and all racial/ethnic groups will be considered Exclusion Criteria: * Prior treatment with epidermal growth factor receptor (EGFR) inhibitors * Uncontrolled intercurrent, use of CYP3A4 modulators * Failed biopsy * Erlotinib treatment \<4 weeks or \<80% of planned regimen at the end of week 4 * HCC development during the study **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** Yujin.Hoshida@UTSouthwestern.edu **Name:** Yujin Hoshida, MD, PhD **Phone:** 214-648-3111 **Role:** CONTACT **Contact 2:** **Email:** Amit.Singal@UTSouthwestern.edu **Name:** Amit Singal, MD, MS **Phone:** 214-648-3111 **Role:** CONTACT ### IPD Sharing Statement Module **Description:** No IPD will be shared with other researchers. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000000230 - Term: Adenocarcinoma - ID: D000008113 - Term: Liver Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004066 - Term: Digestive System Diseases - ID: D000008107 - Term: Liver Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: HIGH - As Found: Hepatocellular Carcinoma - ID: M11103 - Name: Liver Cirrhosis - Relevance: HIGH - As Found: Cirrhosis, Liver - ID: M8485 - Name: Fibrosis - Relevance: HIGH - As Found: Cirrhosis - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M11113 - Name: Liver Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000006528 - Term: Carcinoma, Hepatocellular - ID: D000008103 - Term: Liver Cirrhosis - ID: D000005355 - Term: Fibrosis ### Intervention Browse Module - Ancestors - ID: D000092004 - Term: Tyrosine Kinase Inhibitors - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M398 - Name: Erlotinib Hydrochloride - Relevance: HIGH - As Found: On study - ID: M2889 - Name: Tyrosine Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: T22 - Name: Tyrosine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069347 - Term: Erlotinib Hydrochloride ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01438879 **Brief Title:** Lymphocytic Herpesviruses and Cerebrospinal Fluid Polymerase Chain Reaction (PCR) **Official Title:** Molecular Methods in the Etiological Diagnostics of Acute Central Nervous System Infections: Lymphocytic Herpesviruses and PCR #### Organization Study ID Info **ID:** R11077 #### Organization **Class:** OTHER **Full Name:** PaijatHame Central Hospital ### Status Module #### Completion Date **Date:** 2013-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2011-09-22 **Type:** ESTIMATED **Last Update Submit Date:** 2011-09-21 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2013-10 **Type:** ESTIMATED #### Start Date **Date:** 2011-10 **Status Verified Date:** 2011-09 #### Study First Post Date **Date:** 2011-09-22 **Type:** ESTIMATED **Study First Submit Date:** 2011-09-20 **Study First Submit QC Date:** 2011-09-21 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Turku #### Lead Sponsor **Class:** OTHER **Name:** PaijatHame Central Hospital #### Responsible Party **Investigator Affiliation:** PaijatHame Central Hospital **Investigator Full Name:** Laura Kupila **Investigator Title:** Specialist in neurology, MD PhD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Enterovirus and herpes simplex viruses 1 and 2 are the main causative agents of central nervous system infections. Instead, the role of lymphocytic herpesviruses in the etiology of central nervous system (CNS) infections is not clear, even if there is the positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR)-result for the virus. The aim of this study is to evaluate the presence of DNA from lymphocytic herpesviruses in the CSF obtained from the immunocompetent patients with CSF pleocytosis and from the patients with normal CSF leukocyte count. ### Conditions Module **Conditions:** - Central Nervous System Infection **Keywords:** - CSF - PCR - lymphocytic herpesvirus - CNS ### Design Module #### Bio Spec **Description:** CSF white cells + CSF supernatant, Blood white cells and serum **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 40 patients with clinical signs of CNS infection and having CSF pleocytosis. **Label:** pleocytosis group #### Arm Group 2 **Description:** 20 patients not having CNS infection clinically and not having CSF pleocytosis. **Label:** non-pleocytosis group ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Immunocompetent patients with clinical symptoms and signs of central nervous system infections and CSF pleocytosis (pleocytosis group) * Immunocompetent patients without suspicion of CNS infection and no CSF pleocytosis (non-pleocytosis group) Exclusion Criteria: * Suspicion of CNS-infection, eg. encephalitis, but no CSF leukocytosis (pleocytosis group) * Patients without symptoms of CNS infection, but who has CSF pleocytosis of unknown origin (non-pleocytosis group) **Maximum Age:** 80 Years **Minimum Age:** 16 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Residents of the district of Paijat-Hame (200 000 inhabitants). ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** laura.kupila@phsotey.fi **Name:** Laura MA Kupila **Phone:** +358447195940 **Role:** CONTACT #### Locations **Location 1:** **City:** Lahti **Contacts:** ***Contact 1:*** - **Email:** laura.kupila@phsotey.fi - **Name:** Laura Kupila - **Role:** CONTACT ***Contact 2:*** - **Name:** Laura Kupila - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Finland **Facility:** PaijatHame Central Hospital **Zip:** 15850 #### Overall Officials **Official 1:** **Affiliation:** PaijatHame Central Hospital **Name:** Laura MA Kupila **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M5743 - Name: Central Nervous System Infections - Relevance: HIGH - As Found: Central Nervous System Infections - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000002494 - Term: Central Nervous System Infections ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04570579 **Brief Title:** Impact of a Novel Extended Depth of Focus Intraocular Lens on Visual and Lifestyle Enhancement **Official Title:** Impact of a Novel Extended Depth of Focus Intraocular Lens on Visual and Lifestyle Enhancement #### Organization Study ID Info **ID:** EDOF Lifestyle Enhancement #### Organization **Class:** OTHER **Full Name:** Sight Medical Doctors PLLC ### Status Module #### Completion Date **Date:** 2024-04-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-26 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-24 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-12-30 **Type:** ACTUAL #### Start Date **Date:** 2020-10-14 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2020-09-30 **Type:** ACTUAL **Study First Submit Date:** 2020-09-13 **Study First Submit QC Date:** 2020-09-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Alanna Nattis, DO #### Responsible Party **Investigator Affiliation:** Sight Medical Doctors PLLC **Investigator Full Name:** Alanna Nattis, DO **Investigator Title:** Director of Clinical Research, Ophthalmologist **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The introduction of presbyopia-correcting intraocular lenses (PC-IOLs) has provided cataract and refractive surgeons the ability to provide patients with a wider range of visual success and spectacle independence post-cataract surgery.Multifocal (MFIOL) IOLs have the ability to provide near and distance vision, and in the case of trifocal IOLs, near, intermediate and distance. Despite the significant technological evolution of MFIOL's, the potential for visual disturbances, such as glare, halos and starbursts still exists-and in much greater frequency compared to their monofocal counterparts. Extended depth of focus (EDOF) IOLs aim to provide patients with a functional range of vision, with a similar visual disturbance profile to a monofocal lens. In this way, this subset of PC-IOL's can offer patients some degree of spectacle independence, with a significantly lower incidence of visual disturbances. The Vivity Extended Vision IOL is the first of its kind to offer Wavefront Stretching technology, providing patients with an excellent extended range of vision from intermediate to distance, as well as some functional near vision. Prior studies have demonstrated very good vision in both bright and dim lighting conditions, as well as a high degree of spectacle independence with the Vivity IOL, as compared to a monofocal IOL. Studies evaluating the ability of the Vivity IOL to provide a significant impact on patient lifestyle (e.g. patient independence from spectacles for most activities with a low rate of visual disturbances) in the United States in a 'real-world' setting have yet to be performed. In addition, influence of pre-and-perioperative variables such as sex, age, prior refractive surgery, IOL formula used, axial length, astigmatism, use of intraoperative aberrometry, femtosecond laser and pupillary expansion devices has yet to be evaluated on the postoperative success of this IOL. This study will be comprised of patients with visually significant cataracts who will undergo cataract extraction with implantation of the spherical and/or toric models of the Vivity Extended Vision (Alcon, Fort Worth TX) intraocular lens. Upon decision of the patient and surgeon to undergo surgery, patients will be offered the option to enroll in this observational study. **Detailed Description:** Presbyopia-correcting intraocular lenses (PC-IOLs) provide cataract and refractive surgeons with an effective treatment option for presbyopia, allowing patients increased spectacle independence post-cataract surgery. Different IOL designs have been developed based on differing optical principals, such as diffractive, refractive and extended depth of focus (EDOF) design. Most commercially available MFIOLs have two optical zones, one that provides distance vision, and the second that provides near vision (i.e. "bifocal IOLs"). Most recently, trifocal IOLs have been released, with the aim of providing a third (intermediate) focal point, and hence an extended range of vision in pseudophakic patients. While being able to provide patients with near, intermediate and distance vision, most MFIOL's carry the risk of increased visual disturbances, such as glare, starbursts, and halos, which for a small percentage of patients may become quite bothersome or even debilitating. Extended depth of focus (EDOF) IOLs aim to provide an extended range of vision from intermediate to distance, with a similar visual disturbance profile to their monofocal counterparts. Prior to recent FDA approval, there was only one other EDOF IOL on the market in the US, which, although provides an extended visual range, still had a significant incidence of starbursts and visual disturbances in some patients. FDA approved in February 2020, the Vivity Extended Vision Lens has demonstrated the ability to provide patients with an extended range of vision, excellent contrast sensitivity and visual disturbance profile comparable to a monofocal IOL, as well as high rates of spectacle independence for most activities. The Vivity Extended Vision IOL (Alcon Laboratories, Fort Worth TX) is an EDOF IOL made of hydrophobic acrylic. This non-diffractive lens was designed to mitigate the effect of presbyopia by providing an extended depth of focus through patented Wavefront Shaping technology. In clinical trials, Vivity has demonstrated significantly better intermediate and near vision as compared to a monofocal IOL, as well as superior spectacle independence scores. Additionally, a validated questionnaire regarding visual disturbances showed the Vivity to have comparable rates of starburst, glare and halos to its monofocal counterpart. In an era where intermediate vision has become very important (e.g. using laptops, tablets, seeing the dashboard in a car), many patients express desire for visual correction at all possible focal points. Vivity appears to deliver this with minimal visual side effects-even less so as compared to other MFIOL's. This is a valuable aspect of Vivity; spectacle independence is an important factor for many patients-however if this is coupled with debilitating glare, haloes or other visual disturbances, dissatisfaction will ultimately result. Multiple studies have explored variables that may influence postoperative success of these MFIOLs, including the impact of dry eye, prior corneal refractive surgery, and proper preoperative consent/expectations. A study has yet to be performed evaluating not only preoperative factors, such as astigmatism, and prior corneal refractive surgery, but also perioperative and intraoperative factors that may also play a role in success of the Vivity IOL implant. In this prospective, nonrandomized "real-world" study, the impact of perioperative factors, such as IOL formulae used, use of femtosecond laser, use of intraoperative aberrometry, as well use of pupillary expansion devices on surgical success will be evaluated. Surgical success will be defined as uncorrected distance, intermediate and near visual acuity (UDVA, UIVA and UNVA, respectively) of 20/40 or better (both monocular and binocular) as well as high levels of patient satisfaction, which will be recorded with a Visual Disturbance Questionnaire, Spectacle Independence Questionnaire, and Visual Quality Questionnaire. Results will provide never-before-published data on important preoperative as well as perioperative factors that may influence success and patient satisfaction with Vivity IOL implantation ### Conditions Module **Conditions:** - Cataract - Cataract Senile - Presbyopia **Keywords:** - cataract - presbyopia-correcting intraocular lens - cataract surgery - refractive cataract surgery ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 46 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This is a prospective, nonrandomized study of patients undergoing bilateral cataract surgery with implantation of the spherical Vivity and/or Vivity toric IOL. Preoperative patient data such as age, sex, prior ocular history, medical history, and intraocular lens calculations/formulae used will be recorded. Uncorrected and best-corrected visual acuity will be measured at distance (4m), intermediate (60cm) and near (40cm). All 3 surveys will be administered prior to surgery (at baseline) and at 3 months postoperative, regarding spectacle independence, visual disturbances, and visual quality. A proper perioperative record will be maintained, documenting planned IOL implantation, actual IOL implant used, use of femtosecond laser, use of intraoperative aberrometry, and use of pupillary expansion devices. Patients will be examined 1 day ("postoperative day 1)", 1 week ("postoperative week 1"), 1 month ("postoperative month 1") and 3 months ("postoperative month 3") following surgery. **Intervention Names:** - Device: Vivity Extended Depth of Focus Intraocular Lens **Label:** Observational cohort ### Interventions #### Intervention 1 **Arm Group Labels:** - Observational cohort **Description:** Patients selected to have bilateral sequential cataract surgery using the Vivity (spherical and/or toric where applicable) intraocular lens implant will subsequently be offered enrollment into this observational study. Visual outcomes will be recorded at postoperative day 1, week 1, month 1 and month 3. **Name:** Vivity Extended Depth of Focus Intraocular Lens **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** Adverse events (e.g. surgical complications) in relation to Vivity IOL implantation will be evaluated at each time point. Any adverse events will be documented/reported and treated, if necessary **Measure:** Adverse events **Time Frame:** Safety measures and assessment for adverse events will be assessed at all time points (baseline, postoperative day 1, postoperative week 1, postoperative month 1, postoperative month 3) #### Primary Outcomes **Description:** Change in uncorrected distance visual acuity between baseline and at 3 months postoperative will be assessed. **Measure:** Visual success - uncorrected distance visual acuity **Time Frame:** Change in visual acuity outcomes will be assessed at baseline and compared to postoperative month 3 **Description:** Change in uncorrected intermediate visual acuity between baseline and at 3 months postoperative will be assessed. **Measure:** Visual success- uncorrected intermediate visual acuity **Time Frame:** Change in visual acuity outcomes will be assessed at baseline and compared to postoperative month 3 **Description:** Change in uncorrected near visual acuity between baseline and at 3 months postoperative will be assessed. **Measure:** Visual success- uncorrected near visual acuity **Time Frame:** Change in visual acuity outcomes will be assessed at baseline and compared to postoperative month 3 **Description:** Change in best-corrected distance visual acuity between baseline and at 3 months postoperative will be assessed. **Measure:** Visual success - best corrected distance visual acuity **Time Frame:** Change in visual acuity outcomes will be assessed at baseline and compared to postoperative month 3 **Description:** Change in best-corrected intermediate visual acuity between baseline and at 3 months postoperative will be assessed. **Measure:** Visual success- best-corrected intermediate visual acuity **Time Frame:** Change in visual acuity outcomes will be assessed at baseline and compared to postoperative month 3 **Description:** Change in best-corrected near visual acuity between baseline and at 3 months postoperative will be assessed. **Measure:** Visual success- best-corrected near visual acuity **Time Frame:** Change in visual acuity outcomes will be assessed at baseline and compared to postoperative month 3 **Description:** Change in responses in regard to patient lifestyle satisfaction using a Visual Disturbance Questionnaire at baseline and 3 months postoperative will be assessed. This will be assessed on a scale of 0 - 4 in severity (0 = no disturbance, 4 = very bothersome disturbance). Total scores will be tallied and compared between baseline and postoperative month 3 responses. **Measure:** Visual quality of life measures - visual disturbances **Time Frame:** Questionnaires will be administered at baseline visit (preoperative) and at 3 months postoperative **Description:** Change in responses in regard to patient lifestyle satisfaction using a Visual Quality Questionnaire at baseline and 3 months postoperative will be assessed. This will be assessed on a scale of 1 - 5 in severity (1 = no issues with vision interfering with daily activities, 5 = vision interfering with nearly every activity listed). Total scores will be tallied and compared between baseline and postoperative month 3 responses. **Measure:** Visual quality of life measures - Visual quality **Time Frame:** Questionnaires will be administered at baseline visit (preoperative) and at 3 months postoperative **Description:** Change in responses in regard to patient lifestyle satisfaction using a Spectacle Independence Questionnaire at baseline and 3 months postoperative will be assessed. This will be assessed on a scale of 0 - 4 in severity (0 = never using spectacles for activities, 4 = always using spectacles for every activity listed). Total scores will be tallied and compared between baseline and postoperative month 3 responses. **Measure:** Visual quality of life measures - spectacle independence **Time Frame:** Questionnaires will be administered at baseline visit (preoperative) and at 3 months postoperative ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Visually significant bilateral cataracts, with planned cataract extraction using phacoemulsification and clear corneal incision * Ability to comprehend and willing to sign informed consent * Ability to complete all required postoperative follow up procedures. * 18 years or older * male or female Exclusion Criteria: * Patients who lack ability to consent, and who cannot provide clear understanding of the surgical procedure as well as possible adverse side effects (e.g. dysphotopsias) of the IOL will be excluded * Patients who are professional night drivers, pilots and those with other occupations for whom induced dysphotopsia could put their career at risk will be excluded * Patients who have preexisting significant ocular pathology, including severe dry eye, retina, optic nerve (including moderate-severe glaucoma) and corneal pathologies (e.g. corneal dystrophy, edema, significant scarring), limiting or affecting visual potential, in the opinion of the surgeon, will be excluded * Patients whose IOL calculations are outside the range available for the Vivity IOL will be excluded. * Patients who have history of past eye trauma with evidence of/suspected zonular laxity, and those with pseudoexfoliation will be excluded. * Patients with prior corneal surgery (namely, radial keratotomy (RK), corneal transplantation of any kind) will be excluded from the study (post-myopic and hyperopic LASIK and PRK patients will be permitted to participate in the study). * Pregnant and/or lactating patients will be excluded from the study. * Patients with perioperative or intraoperative complications that do not allow for implantation of the Vivity IOL will be excluded. * Inability to implant the Vivity IOL will cause immediate release from the study with documented rationale for exit. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subjects will be enrolled from a large clinical ophthalmic practice after having been determined to have visually significant cataracts requiring cataract surgery. ### Contacts Locations Module #### Locations **Location 1:** **City:** Babylon **Country:** United States **Facility:** SightMD **State:** New York **Zip:** 11702 ### IPD Sharing Statement Module **Description:** There is no plan at this time to make IPD data available to other researchers. **IPD Sharing:** NO ### References Module #### References **Citation:** Lichtinger A, Rootman DS. Intraocular lenses for presbyopia correction: past, present, and future. Curr Opin Ophthalmol. 2012 Jan;23(1):40-6. doi: 10.1097/ICU.0b013e32834cd5be. **PMID:** 22081027 **Citation:** Alfonso JF, Fernandez-Vega L, Puchades C, Montes-Mico R. Intermediate visual function with different multifocal intraocular lens models. J Cataract Refract Surg. 2010 May;36(5):733-9. doi: 10.1016/j.jcrs.2009.11.018. **PMID:** 20457363 **Citation:** de Vries NE, Nuijts RM. Multifocal intraocular lenses in cataract surgery: literature review of benefits and side effects. J Cataract Refract Surg. 2013 Feb;39(2):268-78. doi: 10.1016/j.jcrs.2012.12.002. **PMID:** 23332253 **Citation:** Wang SY, Stem MS, Oren G, Shtein R, Lichter PR. Patient-centered and visual quality outcomes of premium cataract surgery: a systematic review. Eur J Ophthalmol. 2017 Jun 26;27(4):387-401. doi: 10.5301/ejo.5000978. Epub 2017 Apr 24. **PMID:** 28574135 **Citation:** Cochener B, Boutillier G, Lamard M, Auberger-Zagnoli C. A Comparative Evaluation of a New Generation of Diffractive Trifocal and Extended Depth of Focus Intraocular Lenses. J Refract Surg. 2018 Aug 1;34(8):507-514. doi: 10.3928/1081597X-20180530-02. **PMID:** 30089179 **Citation:** de Medeiros AL, Jones Saraiva F, Iguma CI, Kniggendorf DV, Alves G, Chaves MAPD, Vilar C, Motta AFP, Carricondo PC, Takashi Nakano C, Nose W, Hida WT. Comparison of visual outcomes after bilateral implantation of two intraocular lenses with distinct diffractive optics. Clin Ophthalmol. 2019 Aug 29;13:1657-1663. doi: 10.2147/OPTH.S202895. eCollection 2019. **PMID:** 31695317 **Citation:** Savini G, Schiano-Lomoriello D, Balducci N, Barboni P. Visual Performance of a New Extended Depth-of-Focus Intraocular Lens Compared to a Distance-Dominant Diffractive Multifocal Intraocular Lens. J Refract Surg. 2018 Apr 1;34(4):228-235. doi: 10.3928/1081597X-20180125-01. **PMID:** 29634837 **Citation:** Williams D, Yoon GY, Porter J, Guirao A, Hofer H, Cox I. Visual benefit of correcting higher order aberrations of the eye. J Refract Surg. 2000 Sep-Oct;16(5):S554-9. doi: 10.3928/1081-597X-20000901-12. **PMID:** 11019871 #### See Also Links **Label:** FDA Summary of Safety and Effectiveness Data: Vivity Extended Vision IOL **URL:** https://www.accessdata.fda.gov/cdrh_docs/pdf/P930014S126B.pdf **Label:** Acrysof IQ Vivity Intraocular Lens Product Information **URL:** https://www.accessdata.fda.gov/cdrh_docs/pdf/P930014S126C.pdf ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases - ID: D000012030 - Term: Refractive Errors ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M14179 - Name: Presbyopia - Relevance: HIGH - As Found: Presbyopia - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M14872 - Name: Refractive Errors - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract - ID: D000011305 - Term: Presbyopia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05442879 **Brief Title:** Knowledge Translation Intervention for ACL Injury Prevention Program in Youth Soccer **Official Title:** The Effects of a Knowledge Translation Intervention With an ACL Prevention Program on Implementation, Injury Rates, and Performance in Youth Soccer Players #### Organization Study ID Info **ID:** HUM00214282 #### Organization **Class:** OTHER **Full Name:** University of Michigan ### Status Module #### Completion Date **Date:** 2024-08-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-17 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-15 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-08-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-07-01 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2022-07-05 **Type:** ACTUAL **Study First Submit Date:** 2022-06-23 **Study First Submit QC Date:** 2022-06-28 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Community Foundation of Greater Flint #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** William Suits **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Anterior cruciate ligament (ACL) injuries of the knee are common in youth soccer players, and show an even higher prevalence in female soccer players. Clinical practice guidelines recommend ACL injury prevention programs (ACL-IPP) to reduce injury risk, yet implementation in amateur youth soccer is low, reducing actual real-world effectiveness. This trial is a pragmatic effectiveness trial for ACL injury prevention for amateur youth soccer players, using a knowledge translation intervention with the Knowledge-to-Action Framework. **Detailed Description:** ACL injury prevention programs (ACL-IPP) are exercise programs recommended by clinical practice guidelines that have been shown to reduce the risk of an ACL injury. However, implementation of these programs is low, which reduces the real-world effectiveness of these programs. This project will assess a knowledge translation intervention with youth soccer programs for implementation of ACL-IPPs utilizing the Knowledge-to-Action Framework. The main educational intervention will be a knowledge translation (KT) intervention between the researchers, and coaches/players of youth soccer programs within the state of Michigan. Specifics of the knowledge translation intervention will or may include focus groups, surveys, in-person training, video handouts, and paper handouts. This will be compared to coaches/teams that are offered a handout that describes an evidence-based ACL-IPP. ### Conditions Module **Conditions:** - Anterior Cruciate Ligament Injuries - Lower Extremity Problem ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 671 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The group participating in the KT intervention program will participate in focus groups, individual meetings, and receive videos, informational handouts and on-field training from the researchers. The researchers and participants will work together to determine barriers and facilitators towards implementation of an ACL-IPP, and create an ACL-IPP that follows established clinical practice guidelines and is individualized to the local contextual needs. **Intervention Names:** - Behavioral: Knowledge Translation Intervention **Label:** Knowledge Translation Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The coaches will receive an educational handout describing an ACL-IPP. **Intervention Names:** - Behavioral: Educational handout **Label:** Educational Handout **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Knowledge Translation Intervention **Description:** The KT intervention utilizes the communications between the teams and the researchers to promote implementation of the ACL-IPPs. The meetings will provide opportunities for mutually beneficial learning from the researchers, and feedback from the coaches on how to best implement strategies through local barriers in order to facilitate necessary changes to promote ACL-IPP usage while adhering to clinical practice guideline recommendations. **Name:** Knowledge Translation Intervention **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Educational Handout **Description:** Educational handout describing a commonly cited ACL-IPP. **Name:** Educational handout **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Reported frequency of implementation of ACL-IPP **Measure:** Uptake of ACL-IPP **Time Frame:** up to 2 years **Measure:** Number of ACL injuries **Time Frame:** up to 2 years #### Secondary Outcomes **Description:** Average change in 5-10-5 (Pro Agility) test time **Measure:** Change in 5-10-5 test time **Time Frame:** 2-4 months **Description:** Average change in forward jumping distance **Measure:** Change in horizontal jump distance **Time Frame:** 2-4 months **Description:** Average change in time spent running 10 meters **Measure:** Change in 10 meter forward run time **Time Frame:** 2-4 months **Description:** Number of reported injuries to the foot, ankle, knee, and hip which cause a player to miss time with team **Measure:** Number of time-loss lower extremity injuries **Time Frame:** up to 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Amateur youth soccer organizations within southern Michigan. Exclusion Criteria: * Players above the age of 19 or below the age of 14 * Teams that have dedicated medical staffing **Healthy Volunteers:** True **Maximum Age:** 19 Years **Minimum Age:** 14 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Flint **Country:** United States **Facility:** University of Michigan-Flint **State:** Michigan **Zip:** 48502 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007718 - Term: Knee Injuries - ID: D000007869 - Term: Leg Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M601 - Name: Anterior Cruciate Ligament Injuries - Relevance: HIGH - As Found: Anterior Cruciate Ligament Injuries - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M10738 - Name: Knee Injuries - Relevance: LOW - As Found: Unknown - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014947 - Term: Wounds and Injuries - ID: D000070598 - Term: Anterior Cruciate Ligament Injuries ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03219879 **Acronym:** NaTel **Brief Title:** Telephone-administered Relapse Prevention for Depression **Official Title:** Telephone-administered Cognitive-behavioral Relapse Prevention for Patients With Chronic and Recurrent Depression: A Multi-center Randomized Clinical Trial #### Organization Study ID Info **ID:** 100019_166009 / 1 #### Organization **Class:** OTHER **Full Name:** University of Zurich ### Status Module #### Completion Date **Date:** 2023-04-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-04-08 **Type:** ACTUAL #### Start Date **Date:** 2017-09-29 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2017-07-18 **Type:** ACTUAL **Study First Submit Date:** 2017-06-20 **Study First Submit QC Date:** 2017-07-13 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Universitätsklinikum Hamburg-Eppendorf **Class:** OTHER **Name:** University Hospital, Zürich #### Lead Sponsor **Class:** OTHER **Name:** University of Zurich #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study determines the effectiveness of telephone-delivered cognitive-behavioral continuation therapy (T-CT) in comparison to usual care in people with recurrent or chronic depression. The primary research question is whether participating in T-CT reduces depressive relapses. The continuation therapy comprises eight therapy sessions delivered over the telephone by a trained therapist over a period of approximately six months following acute-phase psychotherapy. **Detailed Description:** Major depression is a serious mental disorder that often takes a recurrent or chronic course causing enduring individual suffering as well as immense direct and indirect health costs. Research indicates that psychological continuation interventions following successful acute-phase therapy are effective in preventing depressive relapse and recurrence but access to these interventions is limited. Systematic psychological continuation interventions are hardly implemented in health care yet, and research shows that there are obstacles concerning access to and compliance for these interventions in a face-to-face setting underlining the need for alternative ways of delivery. The present study ("NaTel study") aims to investigate the effectiveness of telephone-administered cognitive-behavioral continuation therapy (T-CT) following acute-phase psychotherapy. The primary research question is whether participating in T-CT reduces depressive relapses within an observation period of 18 months compared with usual care alone. T-CT comprises eight therapy sessions delivered over the telephone by a trained therapist over a period of approximately six months after acute-phase therapy. Focus of the structured intervention is to train and foster relapse prevention strategies and to facilitate the transfer of skills acquired during acute-phase therapy to daily life. The effectiveness of T-CT as add-on to usual care is tested in a two-parallel group, multicenter, evaluator-blind clinical trial in patients with chronic/persistent or recurrent depressive disorder. Upon acute-phase therapy termination patients who have responded to cognitive behavioral therapy are randomized either to T-CT or usual care alone. Primary outcome of this study is relapse of a depressive episode. Relapse is determined by investigators blind to the study conditions based on clinical interviews conducted at months 6, 12, and 18 of follow-up. Further secondary outcome criteria are assessed with interviews and self-report questionnaires at various time points during follow-up. Overall, the study lasts approximately 48 months. ### Conditions Module **Conditions:** - Depressive Disorder **Keywords:** - Relapse prevention - Persistent depressive disorder - Recurrent depressive disorder - Telephone-based intervention - Cognitive behavioral therapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 201 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Cognitive-behavioral continuation therapy (T-CT) delivered over the telephone by trained psychotherapist **Intervention Names:** - Behavioral: Telephone-administered continuation therapy **Label:** Telephone-administered continuation therapy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Treatment as usual **Intervention Names:** - Other: Usual care **Label:** Usual care **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Telephone-administered continuation therapy **Description:** The intervention includes eight therapy sessions of approx. 50 minutes duration delivered over the telephone by trained psychotherapists over a time period of six months. The intervention is grounded in the principles of psychological continuation therapy and relapse prevention, and includes strategies such as transferring helpful elements of acute-phase cognitive-behavioral therapy (CBT) for depression to daily life. T-CT is offered in addition to usual care. **Name:** Telephone-administered continuation therapy **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Usual care **Description:** Usual care without any study-related intervention **Name:** Usual care **Other Names:** - Treatment as usual (TAU) **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Satisfaction with and acceptability of the telephone-intervention from therapist and participant perspective at 6-month follow-up (T-CT group only) assessed with a customized self-report evaluation questionnaire **Measure:** T-CT acceptability **Time Frame:** 6 months after baseline **Description:** General treatment satisfaction from participant perspective assessed with Client Satisfaction Questionnaire (ZUF-8) at baseline (both groups) and 6-month follow-up (T-CT group only) **Measure:** Treatment satisfaction **Time Frame:** Baseline, and 6 months after baseline **Description:** Participants' self-reported general levels of confidence assessed at baseline, 6- and 12-month follow-up **Measure:** Self-confidence **Time Frame:** Baseline, 6 months, and 12 months after baseline **Description:** Participants' levels of physical activity assessed with the International Physical Activity Questionnaire Short Form (IPAC-SF) at baseline, 6- and 12-month follow-up **Measure:** Physical activity **Time Frame:** Baseline, 6 months, and 12 months after baseline **Description:** Self-efficacy for depression self-management assessed via self-report questionnaire at baseline, 3-, 6- and 12-month follow-up **Measure:** Self-efficacy for depression self-management **Time Frame:** Baseline, 3 months, 6 months, and 12 months after baseline **Description:** Depression-related self-management behaviors assessed via self-report questionnaire at baseline, 3-, 6-, and 12-month follow-up **Measure:** Self-management behaviors **Time Frame:** Baseline, 3 months, 6 months, and 12 months after baseline **Description:** Participants' interpersonal emotion regulation skills assessed with the Interpersonal Emotion Regulation Questionnaire (IERQ) at baseline, 6- and 12-month follow-up **Measure:** Interpersonal emotion regulation skills **Time Frame:** Baseline, 6 months, and 12 months after baseline **Description:** Therapeutic alliance assessed with the Working Alliance Questionnaire-short revised (WAI-SR) from therapist and participant perspective assessed at baseline (both groups), as well as 3- and 6-month follow-up (T-CT group only) **Measure:** Therapeutic alliance **Time Frame:** Baseline, 3 months, and 6 months after baseline #### Primary Outcomes **Description:** Relapse is assessed with the Longitudinal Interval Follow-up Evaluation (LIFE) and defined as a Psychiatric Status Rating (PSR) of PSR=5 or PSR=6 on the 6-point PSR scale for affective disorders for at least two consecutive weeks during a total of 18 months follow-up according to evaluators who are blinded to group allocation **Measure:** Relapse of a major depressive episode **Time Frame:** 6 months, 12 months, and 18 months after baseline #### Secondary Outcomes **Description:** Number of weeks without depressive symptoms defined as weeks with a PSR=1 or PSR=2 on the PSR 6-point scale for affective disorders assessed with the LIFE at month 6, 12 and 18 of follow-up according to blind evaluators **Measure:** Well-weeks **Time Frame:** 6 months, 12 months, and 18 months after baseline **Description:** Self-reported depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 3-, 6-, and 12-month follow-up **Measure:** Depressive symptoms **Time Frame:** Baseline, 3 months, 6 months, and 12 months after baseline **Description:** Health-related quality of life (HrQoL) based on patient self-report assessed with the 12-Item Short Form Health Survey (SF-12) at baseline, 3-, 6- and12-month follow-up **Measure:** Health-related quality of life **Time Frame:** Baseline, 3 months, 6 months, and 12 months after baseline **Description:** Self-reported anxiety symptoms assessed with the General Anxiety Disorder 7 (GAD-7) screener at baseline, 3-, 6-, and 12-month follow-up **Measure:** Anxiety symptoms **Time Frame:** Baseline, 3 months, 6 months, and 12 months after baseline **Description:** Psychosocial functioning assessed with the LIFE-Range of Impaired Functioning Tool (LIFE-RIFT) and Global Assessment of Functioning (GAF) based on monthly ratings by blind evaluators **Measure:** Psychosocial functioning **Time Frame:** 6 months and 12 months after baseline **Description:** Direct and indirect cost derived from health care utilization and productivity loss are assessed with the Client Sociodemographic and Service Receipt Inventory (CSSRI-D) at baseline, 6- and 12-month follow-up **Measure:** Cost of health care utilization **Time Frame:** Baseline, 6 months, and 12 months after baseline **Description:** Health-related quality of life assessments for health economic analyses by the determination of Quality-Adjusted Life Years (QALYs) are based on the EuroQol-five dimension questionnaire five-level version (EQ-5D-5L) administered at baseline, 6- and 12-month follow-up **Measure:** Cost-effectiveness **Time Frame:** Baseline, 6 months, and 12 months after baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Recurrent major depressive disorder or chronic/persistent depressive disorder based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), or first major depressive episode with an elevated risk for relapse (defined as the presence of at least of the following clinical characteristics: index episode duration ≥ six months; severity of the index episode at least moderate; DSM-5 comorbidity; residual symptoms at the end of index treatment) * Having regularly terminated acute-phase CBT for depression (index treatment) * Having achieved therapeutic response during index therapy defined as at least 25%-improvement in depressive symptoms between start and end of acute-phase therapy based on a standardized symptom measure (e.g. PHQ-9, or Beck Depression Inventory; BDI) * Having experienced partial or full remission at the end of the index treatment based on DSM-5 criteria for major depressive disorder * Sufficient command of German language * Having given written informed consent Exclusion Criteria: * Unstable psychopharmacological medication regimen (either with or without antidepressant (AD) medication) at the end of the index treatment, i.e. change in type or dosage of medication envisaged at the end of index treatment * Acute risk for suicide based on clinical practice guidelines; patients with self-reported suicidal ideation are eligible as long as the treatment is deemed safe by the clinician's judgment * A history of or acute psychotic symptoms, bipolar disorder, or organic brain disorder * Severe cognitive impairment based on clinical evaluation during index treatment **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Stuttgart **Country:** Germany **Facility:** Institut für Klinische Psychologie, Krankenhaus Bad Cannstatt, Klinikum Stuttgart **Location 2:** **City:** Bern **Country:** Switzerland **Facility:** Universitätsklinik für Psychiatrie und Psychotherapie, Universität Bern **Location 3:** **City:** Brugg **Country:** Switzerland **Facility:** Zentrum Psychiatrie und Psychotherapie stationär, Psychiatrische Dienste Aargau AG **Location 4:** **City:** Gais **Country:** Switzerland **Facility:** Zentrum für Psychiatrie und Psychotherapie, Klinik Gais AG **Location 5:** **City:** Herisau **Country:** Switzerland **Facility:** Klinik für Psychiatrie und Psychotherapie, Psychiatrisches Zentrum AR **Location 6:** **City:** Langenthal **Country:** Switzerland **Facility:** Klinik SGM Langenthal **Zip:** 4900 **Location 7:** **City:** Meiringen **Country:** Switzerland **Facility:** Zentrum für seelische Gesundheit, Privatklinik Meiringen **Zip:** 3860 **Location 8:** **City:** Oberwil **Country:** Switzerland **Facility:** Zentrum für Psychiatrie und Psychotherapie Klinik Zugersee, Triaplus AG **Location 9:** **City:** Zug **Country:** Switzerland **Facility:** Psychiatrische und Psychotherapeutische Spezialklinik für Frauen, Klinik Meissenberg AG **Location 10:** **City:** Zürich **Country:** Switzerland **Facility:** Klinik für Psychiatrie und Psychotherapie, UniversitätsSpital Zürich **Location 11:** **City:** Zürich **Country:** Switzerland **Facility:** Praxisstelle Psychotherapie, Universität Zürich #### Overall Officials **Official 1:** **Affiliation:** University of Zurich **Name:** Birgit Watzke, Prof **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Zurich **Name:** Markus Wolf, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** Brief abstract of the trial **URL:** http://www.psychologie.uzh.ch/de/fachrichtungen/klipfor/forschung/forschungsprojekte.html ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depressive Disorder - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depressive Disorder - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Relapse - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012008 - Term: Recurrence - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05271279 **Brief Title:** A Study of OVV-01 Injection in Combination With IBR900 Cell Injection in Patients With Advanced Malignant Tumors **Official Title:** A Single-Arm, Open-Label, Investigator-Initiated Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Oncolytic Virus Injection (OVV-01) in Combination With IBR900 Cell Injection in Patients With Advanced Malignant Tumors #### Organization Study ID Info **ID:** BR20210414003 #### Organization **Class:** OTHER **Full Name:** Beijing Boren Hospital ### Status Module #### Completion Date **Date:** 2022-08-29 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-02 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-31 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2022-08-29 **Type:** ACTUAL #### Start Date **Date:** 2021-12-24 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2022-03-09 **Type:** ACTUAL **Study First Submit Date:** 2022-02-23 **Study First Submit QC Date:** 2022-03-04 **Why Stopped:** Research and development strategy adjustment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Beijing Boren Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a prospective, multi-center, open-label, single-arm, investigator-initiated clinical trial to evaluate the safety and efficacy of oncolytic virus injection (OVV-01) in combination with trained immunity NK (tiNK) cell injection (IBR900) for patients with advanced malignant tumors. **Detailed Description:** In this study, it is planned to enroll about 6-12 subjects with advanced solid tumors or relapsed/refractory lymphomas who have failed in the third-line or higher standard of care in about 1-3 study sites in China. A 2-dose gradient joint exploratory study using the traditional "3+3" mode is adopted in this study. If the high-dose group does not yet reach the MTD, the investigator and funder will decide whether to continue the dose escalation and whether to add a new dose group. 2 dose gradients are used for the OVV-01 injection, and the total infusion dose of IBR900 cell injection is 4.0×10\^9 cells per cycle. OVV-01 injection will be first administered at W1D1 and then at W4D1 followed by every 2 weeks as a treatment cycle, for a total of 6 doses; after the test in the high-dose group is completed, the investigator and sponsor will determine whether to adjust the dosing frequency of OVV-01 (such as once a week) based on the result evaluations. The IBR900 cell injection will be first administered at W1D3 and W1D5 for 2 infusions, and then at W4D3 and W4D5, followed by every 4 weeks as a cycle, for a total of 4 doses, and cell infusions will be conducted at W1, W4, W8 and W12, respectively. ### Conditions Module **Conditions:** - Advanced Solid Tumor - Relapsed/Refractory Lymphoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 2 **Type:** ACTUAL **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** OVV-01 injection combined with IBR900 cell injection, 2 dose gradients are used for the OVV-01 injection, and the total infusion dose of IBR900 cell injection is 4.0×10\^9 cells per cycle. **Intervention Names:** - Biological: OVV-01 Injection+IBR900 Cell Injection **Label:** OVV-01 Injection+IBR900 Cell Injection **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - OVV-01 Injection+IBR900 Cell Injection **Description:** 2 dose gradients are used for the OVV-01 injection, and the total infusion dose of IBR900 cell injection is 4.0×10\^9 cells per cycle. OVV-01 injection will be first administered at W1D1 and then at W4D1 followed by every 2 weeks as a treatment cycle, for a total of 6 doses; after the test in the high-dose group is completed, the investigator and sponsor will determine whether to adjust the dosing frequency of OVV-01 (such as once a week) based on the result evaluations. The IBR900 cell injection will be first administered at W1D3 and W1D5 for 2 infusions, and then at W4D3 and W4D5, followed by every 4 weeks as a cycle, for a total of 4 doses, and cell infusions will be conducted at W1, W4, W8 and W12, respectively. **Name:** OVV-01 Injection+IBR900 Cell Injection **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** To evaluate the safety and tolerability of OVV-01 injection and IBR900 cell injection **Measure:** Dose limiting toxicity (DLT) **Time Frame:** 7 weeks after initial administration **Description:** The incidence and severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and the correlation between AEs and OVV-01 injection combined with IBR900 cell injection **Measure:** Adverse events (AEs) **Time Frame:** 24 weeks after initial administration #### Secondary Outcomes **Description:** To evaluate the effectivity of OVV-01 injection and IBR900 cell injection **Measure:** Objective response rate (ORR) **Time Frame:** Up to 1 year after administration **Description:** To evaluate the effectivity of OVV-01 injection and IBR900 cell injection **Measure:** Progression-free survival (PFS) **Time Frame:** Up to 1 year after administration **Description:** To evaluate the effectivity of OVV-01 injection and IBR900 cell injection **Measure:** Overall survival (OS) **Time Frame:** Up to 1 year after administration **Description:** To evaluate the effectivity of OVV-01 injection and IBR900 cell injection **Measure:** Disease control rate (DCR) **Time Frame:** Up to 1 year after administration **Description:** To evaluate the effectivity of OVV-01 injection and IBR900 cell injection **Measure:** Duration of overall response (DOR) **Time Frame:** Up to 1 year after administration **Description:** Blood samples will be collected at specified time points to detect the concentration of OVV-01 in peripheral blood and to evaluate the PK parameters **Measure:** Peak plasma concentration of OVV-01 **Time Frame:** 14 days after the last administration **Description:** Blood samples will be collected at specified time points to detect the concentration of IBR900 cells in peripheral blood and to evaluate the PK parameters **Measure:** Peak plasma concentration of IBR900 cells **Time Frame:** 16 days after initial administration **Description:** To observe and evaluate the time, titer, and subject rate of antibody development after administration **Measure:** Plasma concentration of anti-VSV-G antibody and neutralizing antibody **Time Frame:** 16 weeks after initial administration ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Subjects who are ≥18 years old and ≤75 years old, male or female; 2. Subjects with advanced malignant tumors with the primary lesions and/or metastatic lesions diagnosed by histopathology/cytological examinations, including but not limited to: melanoma, the head and neck squamous cell carcinoma, cervical carcinoma, osteosarcoma, nasopharyngeal carcinoma, breast carcinoma, lung carcinoma, colorectal carcinoma, liver carcinoma, gastric carcinoma, lymphoma, etc.; 3. Subjects with solid tumors or relapsed/refractory lymphomas who have failed in the third-line or higher standard of care; 4. Subjects with at least one measurable lesion (non-lymph node lesion with longest diameter ≥10 mm, or lymph node lesion with short diameter ≥15 mm) according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Evaluation Criteria for Efficacy of Lymphoma Lugano 2014; 5. Subjects with the Eastern Cooperative Oncology Organization (ECOG) score of 0-2; 6. Subjects with the expected survival ≥ 3 months; 7. Subjects with adequate bone marrow function: * White blood cell (WBC)≥3.0×10\^9/L; * Neutrophils (ANC)≥1.5×10\^9/L (cannot use the colony stimulating factor within 3 days before the test); * Lymphocyte count ≥6.0×10\^8/L; * Platelet count ≥100×10\^9/L; * Hemoglobin ≥9.0 g/dL; 8. Subjects with adequate liver function and kidney function: * Total bilirubin ≤1.5 times the upper limit of normal (ULN), or total bilirubin ≤3.0×ULN for subjects with liver metastases. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5×ULN, or AST and ALT≤5×ULN for subjects with liver metastases; * Serum creatinine≤1.5×ULN, or creatinine clearance ≥50 ml/min (calculated according to Cockcroft/Gault formula); 9. Coagulation function * For subjects not receiving anticoagulation therapy: international normalized ratio (INR)≤1.5×ULN, activated partial thromboplastin time (APTT)≤1.5×ULN * For subjects receiving anticoagulation therapy: INR≤ 2-3×ULN, APTT≤ 2-3×ULN Female subjects of childbearing age who is negative in the pregnancy test within 14 days before inclusion. Female subjects of childbearing age and male subjects whose partners are females of childbearing age must agree to use at least one medically approved birth control (such as surgical sterilization, oral contraceptives, intrauterine devices, sexual desire control or barrier contraception in combination with spermicides, etc.); 11.The subjects should voluntarily participate in the study, sign the informed consent forms, have good compliance, and cooperate with the follow-up visits. Exclusion Criteria: 1. Subjects without measurable lesions; 2. Subjects with symptomatic brain metastases (but subjects who have asymptomatic brain metastases or have been clinically stable for more than 3 months with local treatment can be included in the study); 3. Subjects who have received radiotherapy for the target lesion within 2 months; 4. Subjects with other active malignant tumors that require simultaneous treatment; 5. Subjects who are known to be allergic to the study drug or its active ingredients and excipients; 6. Subjects who have received or been receiving or still need to receive other investigational drug or antiviral treatments within 4 weeks before administration; 7. Subjects who are going to undergo or have received tissue/organ transplantation; 8. Subjects who have active infections or fever \>38.5°C of unknown cause during the screening phase and before the first dose; 9. Subjects with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening; 10. Subjects who are positive in the treponema pallidum serology test; 11. Subjects with the medical history of known human immunodeficiency virus (HIV) positive or known acquired immunodeficiency syndrome (AIDS); 12. Subjects with active hepatitis. Hepatitis B: HBeAg (+), HBcAb (+) in combination with+ HbsAg (+); for HBsAg (+) or HBcAb (+), the detection value of HBV DNA is ≥1000 IU/ml; hepatitis C: hepatitis C virus antibody (HCV Ab) positive and the detection value of HCV RNA is ≥1000 IU/ml; co-infection of hepatitis B and C; 13. Subjects who have received anti-tumor drug therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, and immunotherapy within 4 weeks before the first administration except the following: * nitrosourea or mitomycin C within 6 weeks before the first administration of the study drug; * oral fluorouracil and small-molecular targeted drugs within 2 weeks before the first administration of the study drug or 5 half-lives of the drug (whichever is longer); * traditional Chinese medicine with anti-tumor indications within 2 weeks before the first administration of the study drug; 14. Subjects with cardiovascular disorders meet any of the following: * Congestive heart failure with heart function ≥ New York Heart Association (NYHA) III; * Severe arrhythmia requiring drug therapy; * Acute myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass, and stent within 6 months before the first administration; * Left ventricular ejection fraction (LVEF)\< 50%; * Corrected QTc interval \> 450 ms for male and\> 470 ms for female, or risk factors for torsade de pointes ventricular tachycardia, such as clinically significant hypokalemia judged by the investigator, family history of long QT syndrome, or familial arrhythmia history (such as pre-excitation syndrome); * Uncontrolled hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg with treatment with standardized antihypertensive drugs) 15. Subjects with active autoimmune diseases or a history of autoimmune diseases but may be relapsed; but subjects with the following diseases are not excluded and can be further screened: * Type 1 diabetes mellitus; * Hypothyroidism (if only hormone replacement therapy can be used to control); * Controlled celiac disease; * Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia); * Any other diseases that will not relapse without external triggers; 16. Subjects with any diseases who need to use glucocorticoids (prednisone \>10 mg/day or equivalent doses of similar drugs) or other immunosuppressive agents for systemic treatment within 14 days before administration of the study drug, but is using or have used any of the following steroids can be included: * Adrenaline replacement steroids (prednisone ≤10 mg/day or equivalent dose of similar drugs); * Local, ophthalmic, intra-articular, intranasal or inhaled corticosteroids with minimal systemic absorption; * Prophylactically short-term (≤7 days) use of corticosteroids (such as allergy to contrast agents) or for the treatment of non-autoimmune diseases (such as delayed hypersensitivity reactions caused by contact allergens); 17. Subjects with psychiatric disorders, alcoholism, heavy smoking, drug use or drug abuse, etc.; 18. Female subjects who are pregnant or breastfeeding, or who are expected to become pregnant during the study (from the screening visit until 180 days after administration) and male subjects who are expected to conceive their partners; 19. Subjects whose adverse reactions of prior anti-tumor treatments have not yet recovered to CTCAE v5.0 Grade 1 (except for the alopecia); 20. Subjects who have serious uncontrollable diseases or other conditions that may affect the treatment of this study and are not suitable to participate in this study as determined by the investigator. Other conditions not suitable for enrollment at investigators' decision. **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** Beijing Boren Hospital **State:** Beijing **Zip:** 100070 #### Overall Officials **Official 1:** **Affiliation:** Beijing Boren Hospital **Name:** Kai Hu, MD/PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00002079 **Brief Title:** Phase II Study of the Safety and Surrogate Marker Efficacy of Butyldeoxynojirimycin (SC-48334) and AZT in Symptomatic HIV-1 Infected Patients With 200 - 500 CD4+ Cells/mm3. (NOTE: Asymptomatic HIV-1 Infected Patients Also Eligible) **Official Title:** Phase II Study of the Safety and Surrogate Marker Efficacy of Butyldeoxynojirimycin (SC-48334) and AZT in Symptomatic HIV-1 Infected Patients With 200 - 500 CD4+ Cells/mm3. (NOTE: Asymptomatic HIV-1 Infected Patients Also Eligible) #### Organization Study ID Info **ID:** 057B #### Organization **Class:** INDUSTRY **Full Name:** NIH AIDS Clinical Trials Information Service #### Secondary ID Infos **ID:** NS8-91-02-009 ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2005-06-24 **Type:** ESTIMATED **Last Update Submit Date:** 2005-06-23 **Overall Status:** COMPLETED **Status Verified Date:** 1993-03 #### Study First Post Date **Date:** 2001-08-31 **Type:** ESTIMATED **Study First Submit Date:** 1999-11-02 **Study First Submit QC Date:** 2001-08-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** G D Searle ### Description Module **Brief Summary:** To assess the dose-related antiviral effects of SC-48334 and zidovudine (AZT) administered in combination or individually in HIV-1 positive patients with 200 - 500 CD4+ cells/mm3. To determine the safety of escalating doses of SC-48334 when administered in combination with any of three doses of AZT to symptomatic HIV-1 positive patients with 200 - 500 CD4+ cells/mm3, and to assess the pharmacokinetics of the two drugs, given separately and in combination. ### Conditions Module **Conditions:** - HIV Infections **Keywords:** - Zidovudine - 1-Deoxynojirimycin ### Design Module #### Design Info **Primary Purpose:** TREATMENT **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Butyldeoxynojirimycin **Type:** DRUG #### Intervention 2 **Name:** Zidovudine **Type:** DRUG ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria Patients must have: * Documented HIV infection. * CD4 cell count 200 - 500 cells/mm3. * Prior therapy with 12 - 48 weeks of AZT. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: * Clinically significant diarrhea without definable cause (\> 3 liquid stools per day for more than 7 days within 6 months prior to study entry). * Diarrhea, as above, with known non-HIV-related cause occurring within 1 month prior to study entry. * Symptoms meeting CDC criteria for AIDS classification. * Fever as a constitutional sign of HIV disease (\> 38.5 degrees C persisting for more than 14 consecutive days or for more than 15 days in any given 30-day period prior to study entry). * Malignancies, other than basal cell carcinoma and Kaposi's sarcoma (provided patient has fewer than 10 Kaposi's sarcoma lesions, no non-skin lesions, and no requirement for systemic treatment). * Significant organ dysfunction. * Known hypersensitivity to SC-48334 or AZT or related compounds. Concurrent Medication: Excluded: * Any investigational drug other than SC-48334. * Any anti-HIV drug other than AZT. * Cancer chemotherapy. Patients with the following prior conditions are excluded: * History of cataracts or known increased risk of cataract formation. * Known hypersensitivity to SC-48334 or AZT or related compounds. * History of lactose intolerance. Prior Medication: Excluded: * Prior SC-48334. * Cancer chemotherapy within 6 months prior to study entry. * Treatment with any investigational drug or any drug with anti-HIV activity, other than AZT, within 30 days prior to study entry. Prior Treatment: Excluded: Whole-body irradiation within 6 months prior to study entry. Current use of illicit substances, or abuse of alcohol, which would limit compliance with the protocol. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Francisco **Country:** United States **Facility:** Dr Marcus Conant **State:** California **Zip:** 94115 **Location 2:** **City:** Tarzana **Country:** United States **Facility:** Shared Med Research Foundation **State:** California **Zip:** 91356 **Location 3:** **City:** Miami Beach **Country:** United States **Facility:** Stratogen of South Florida **State:** Florida **Zip:** 33140 **Location 4:** **City:** Tampa **Country:** United States **Facility:** Saint Joseph's Hosp / Infectious Disease Rsch Institute **State:** Florida **Zip:** 33614 **Location 5:** **City:** Atlanta **Country:** United States **Facility:** West Paces Clinical Research Incoporated **State:** Georgia **Zip:** 30327 **Location 6:** **City:** Pittsburgh **Country:** United States **Facility:** Dr Samuel W Golden **State:** Pennsylvania **Zip:** 15218 **Location 7:** **City:** Dallas **Country:** United States **Facility:** Dallas Veterans Administration Med Ctr **State:** Texas **Zip:** 75216 **Location 8:** **City:** Fort Worth **Country:** United States **Facility:** Dr Daniel Barbero **State:** Texas **Zip:** 76104 **Location 9:** **City:** Houston **Country:** United States **Facility:** Park Plaza Hosp **State:** Texas **Zip:** 77004 ### References Module #### References **Citation:** Fischl MA, Resnick L, Coombs R, Kremer AB, Pottage JC Jr, Fass RJ, Fife KH, Powderly WG, Collier AC, Aspinall RL, et al. The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3. J Acquir Immune Defic Syndr (1988). 1994 Feb;7(2):139-47. **PMID:** 7905523 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000015229 - Term: Sexually Transmitted Diseases, Viral - ID: D000012749 - Term: Sexually Transmitted Diseases - ID: D000016180 - Term: Lentivirus Infections - ID: D000012192 - Term: Retroviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000007153 - Term: Immunologic Deficiency Syndromes - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: HIGH - As Found: HIV Infections - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: LOW - As Found: Unknown - ID: M17933 - Name: Sexually Transmitted Diseases, Viral - Relevance: LOW - As Found: Unknown - ID: M18640 - Name: Lentivirus Infections - Relevance: LOW - As Found: Unknown - ID: M15026 - Name: Retroviridae Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10199 - Name: Immunologic Deficiency Syndromes - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015658 - Term: HIV Infections ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018894 - Term: Reverse Transcriptase Inhibitors - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000019380 - Term: Anti-HIV Agents - ID: D000044966 - Term: Anti-Retroviral Agents - ID: D000065089 - Term: Glycoside Hydrolase Inhibitors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: CaAg - Name: Cardiotonic Agents ### Intervention Browse Module - Browse Leaves - ID: M351060 - Name: Miglustat - Relevance: HIGH - As Found: ACG - ID: M17920 - Name: Zidovudine - Relevance: HIGH - As Found: Intraoperative - ID: M19750 - Name: 1-Deoxynojirimycin - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M20935 - Name: Reverse Transcriptase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M21350 - Name: Anti-HIV Agents - Relevance: LOW - As Found: Unknown - ID: M25428 - Name: Anti-Retroviral Agents - Relevance: LOW - As Found: Unknown - ID: M5557 - Name: Cardiac Glycosides - Relevance: LOW - As Found: Unknown - ID: M30447 - Name: Glycoside Hydrolase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000059896 - Term: Miglustat - ID: D000015215 - Term: Zidovudine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04608279 **Acronym:** PROTI-PREMA **Brief Title:** Urinary Creatinin/Protein Ratio in Preterms **Official Title:** Evolution of the Proteinuria / Creatininuria Ratio in the First Month of Life in the Preterm Infant #### Organization Study ID Info **ID:** 2017/CHU/09 #### Organization **Class:** OTHER **Full Name:** Centre Hospitalier Universitaire de la Réunion ### Status Module #### Completion Date **Date:** 2020-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-10-29 **Type:** ACTUAL **Last Update Submit Date:** 2020-10-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-01 **Type:** ACTUAL #### Start Date **Date:** 2017-01 **Type:** ACTUAL **Status Verified Date:** 2020-10 #### Study First Post Date **Date:** 2020-10-29 **Type:** ACTUAL **Study First Submit Date:** 2019-10-08 **Study First Submit QC Date:** 2020-10-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre Hospitalier Universitaire de la Réunion #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** From the first days of life, the newborn presents a "physiological" proteinuria explained by the coexistence of a glomerular and tubular immaturity, all the more marked as the gestational age (GA) is weak. In the child term, proteinuria decreases the first month and its persistence is the marker of kidney damage. The persistence of proteinuria in preterm infants is also considered a marker of renal impairment; however, neither the "physiological" values nor the pattern of urinary excretion of proteins in the first month of life are known. The proteinuria / creatininuria ratio is a validated indicator of proteinuria, as it is correlated with 24-hour urine proteinuria. ### Conditions Module **Conditions:** - Preterm Infant - Renal Failure ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 124 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Ratio of proteinuria / creatinine to P1 (D0), P2 (D2 or D3), P3 (D5 or D6), P4 (W2), P5 (W3) and P6 (W4). **Measure:** Evolution in time of Ratio of proteinuria / creatininuria **Time Frame:** Day 0, Day 2 or Day 3, Day 5 or Day 6, Week 2, Week 3, Week 4 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Premature gestational age at birth superior or equal to 32 week of amenorrhea hospitalized in the intensive care unit or neonatal intensive care unit of the University Hospital of Reunion, southern site, Saint Pierre, in the first 24 hours of life * Informed consent form Legal representant Exclusion Criteria: * Renal malformation known in antenatal **Maximum Age:** 2 Days **Minimum Age:** 1 Day **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** Premature gestational age at birth superior or equal to 32 week of amenorrhea ### Contacts Locations Module #### Locations **Location 1:** **City:** Saint Pierre **Country:** France **Facility:** Centre Hospitalier de La Réunion **State:** La Réunion **Zip:** 97448 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007752 - Term: Obstetric Labor, Premature - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M25869 - Name: Premature Birth - Relevance: HIGH - As Found: Preterm - ID: M14368 - Name: Proteinuria - Relevance: LOW - As Found: Unknown - ID: M26718 - Name: Renal Insufficiency - Relevance: LOW - As Found: Unknown - ID: M10772 - Name: Obstetric Labor, Premature - Relevance: LOW - As Found: Unknown - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000047928 - Term: Premature Birth ### Misc Info Module - Version Holder: 2024-05-24