cyrilzakka/clinical-trials huggingface dataset:
Pharmacokinetic Boosting of Osimertinib

The main objective of this study is to evaluate if systemic exposure of osimertinib (i.e. AUC) is increased when osimertinib is co-administered with cobicistat in patients with relatively low plasma trough concentration while receiving the standard osimertinib dose.

Osimertinib is a new targeted agent registered for the treatment of patients with EGFR-mutated NSCLC. However, the costs of those new treatments are extremely high. Osimertinib is mainly metabolized by CYP3A4, and partially by CYP3A5. Combination of osimertinib with a strong CYP3A4-inhibitor may result in a smaller first-pass effect and a decreased clearance of osimertinib, thereby increasing the exposure to osimertinib.

Cobicistat is a strong CYP3A4-inhibitor, this mechanism may be used to boost osimertinib, as is done for other drugs, mainly drugs used to treat HIV-infected patients.

Using this personalized treatment approach and combining the concepts of therapeutic drug monitoring (TDM) and pharmacokinetic boosting, osimertinib therapy could become much more cost-effective. By reducing the necessary dose of osimertinib, this strategy may ultimately result in a significant reduction in drug costs, as the additional expenditure for the CYP3A4 inhibitor and blood sample analysis are negligible compared to the price of osimertinib.

Eligibility Criteria:
Inclusion Criteria:

* Patients with EGFR-mutated NSCLC receiving standard treatment with osimertinib for at least 2 months (steady state), without any signs of disease progression, or during treatment beyond progression, if treatment continuation is expected for multiple months. After anticipated EMA approval of osimertinib adjuvant therapy, patients on adjuvant osimertinib treatment may also participate on the following conditions; If they are receiving standard treatment with osimertinib for at least 2 months (steady state), and if treatment will be continued for a longer period than necessary for participation in the OSIBOOST trial.
* Age ≥ 18 years
* WHO performance status ≤ 2.
* Able and willing to give written informed consent.
* Able and willing to undergo blood sampling for pharmacokinetic analysis.
* Patients with osimertinib plasma trough concentration below 195 ng/mL. Plasma trough concentration of osimertinib will be determined in another study (METC MUMC: 2018-0800).

Exclusion Criteria:

* Any concurrent medication that is known to strongly inhibit or induce CYP3A4.
* Any concurrent medication that is primarily metabolized by CYP3A4 with a narrow therapeutic window.
* Impairment of gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
* Refusing to refrain from consuming CYP3A4 influencing products, e.g. grapefruit(juice), St. John's wort.
* Pregnancy or breast feeding
* Child-Pugh score class C, chronic liver disease.
Comparison of Scores for Early Brain Damage Assessment at Intensive Care Unit Admission After Out of Hospital Cardiac Arrest

Even in patients with successful return of spontaneous circulation (ROSC), outcome after cardiac arrest remains poor. The overall in-hospital survival rate widely varies both worldwide and across communities, from 1 to 4 folds according to circumstances of arrest and post-resuscitation interventions. Several studies have already shown that early interventions performed after ROSC, such as treatment of the cause, targeted temperature management, optimal hemodynamic management and extra-corporeal life support in selected patients, could improve the outcome in post-cardiac arrest patients. However, the decision process regarding the allocation of these resources, in parallel with the management of patients' proxies, remains a complex challenge for physicians facing these situations. Consequently, several prediction models and scores have been developed in order to stratify the risk of unfavorable outcome and to discriminate the best candidates for post-resuscitation interventions. Overall, several scores exist, but external validation are lacking and direct comparisons are needed to assess relative interest of scoring systems. Indeed, establishing the optimal scoring system is crucial, for optimal treatment allocation and appropriate information to relatives.


Eligibility Criteria:
Inclusion Criteria:

- All adult patients, major, admitted to intensive care after out-of-hospital cardiac arrest and comatose (defined by Glasgow score ≤ 8) on admission.

Exclusion Criteria:

* cardiac arrest occurring intra-hospital,
* minor patient,
* major patient under guardianship,
* protected persons,
* prior inclusion in the study
Genome-wide Analysis of Single Nucleotide Polymorphisms of Brain Arteriovenous Malformations and Cerebral Aneurysm

Test single nucleotide polymorphisms (SNP's) in ruptured and unruptured aneurysm tissue to identify a genetic difference between the two types of aneurysms; and to test SNP's in arteriovenous malformation tissue to identify a genetic link.


Eligibility Criteria:
Inclusion Criteria:

* All adult patients between the ages of 18 and 89 that are having open surgical resection of an AVM or clipping of an aneurysm will be included

Exclusion Criteria:
Virtual Reality for Postoperative Pain Management

This trial studies an active virtual reality (VR) experience as a means for non-pharmacologic postoperative pain management among patients after head and neck surgery. Investigators will assess differences in pain scores, analgesic use, and subjective patient experiences between patients participating in a VR activity and patients participating in the same activity using a smartphone.

Management of postoperative pain after head and neck surgery is complex, and has received increased attention to improve patient recovery and quality of life. Narcotic analgesics are frequently utilized in postoperative pain management, but these have risks including nausea, sedation, constipation, and dependence. Multimodal analgesia can reduce narcotic use and improve recovery, but medical comorbidities may contraindicate the use of certain medications. Non-pharmacologic measures for postoperative pain control may provide novel and cost-effective strategies to confront this complex issue.

Patients undergoing head and neck surgery will be randomly allocated to participate in an immersive experience in VR, or to participate in a similar experience on a two-dimensional screen using a smartphone.

Eligibility Criteria:
Inclusion Criteria:

* Patients who have undergone head and neck surgery with an average pain score of 3 or greater out of 10 during the 24 hours preceding the screening
* Are able to provide informed consent
* Are not in the intensive care unit (ICU)

Exclusion Criteria:

* Symptoms concerning for an active respiratory infection including fever, cough, and shortness of breath or confirmed respiratory infection
* Active eye discharge
* Active nausea or vomiting
* History of seizure, epilepsy, or hypersensitivity to flashing light
* History of motion sickness or vertigo
* Have wound dressings on the head or neck that prevent comfortable and safe use of the virtual reality headset
Quantitative Ultrasonography (US) Evaluation on Femoral Condyle Cartilage

The purpose of this study is to investigate the feasibility of using quantitative ultrasonography (US) evaluation to determine the severity of osteoarthritic femoral condyle cartilage erosion.


Eligibility Criteria:
Inclusion Criteria:

* Patients with knee OA who were going to receive total knee arthroplasty

Exclusion Criteria:

* Patients with inflammatory arthritis (e.g. rheumatic arthritis) and infectious disease (e.g. hepatitis B)
Safety and Efficacy Study of CUBICIN (Daptomycin) Under Conditions of Actual Use

The purpose of this study is to monitor the safety and efficacy of CUBICIN under conditions of actual use in patients who are diagnosed with complicated Skin and Skin Structure infection (cSSI) or Staphylococcus aureus bacteria including right-sided endocarditis and are prescribed CUBICIN by their physician.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of cSSSI known or suspected to be due to gram-positive bacteria
* Diagnosis of right-sided endocarditis with one or more positive culture for S. aureus within two days prior to initiation of medication
* Prescribed daptomycin by patient's attending physician

Exclusion Criteria:

* Known allergic or serious adverse reaction to daptomycin
* Patients with pneumonia
* Patients with baseline CPK values \>1000 U/L or 5x ULN
New Local Treatment of Radiation-induced Proctitis

A prospective single-center observational study to evaluate the effectiveness of a local treatment with a mixture of hyaluronic acid, chondroitin sulfate and poloxamer 407 in patients with radiation-induced proctitis.


Eligibility Criteria:
Inclusion Criteria:

* proven symptomatic acute or chronic radiation-induced proctitis;
* current or prior radiation therapy in the pelvic area;
* patients with complications connected to the radiation therapy.

Exclusion Criteria:

* lack of informed consent;
* non-adherence to study protocol;
* pregnancy.
Letrozole add-on in the Treatment of Cesarean Scar Pregnancy

It is hypothesized that the inhibition of estradiol production by letrozole may interfere with physiological effects of progesterone necessary to maintain the pregnancy. There is no reference treatment of cesarean scar pregnancy (CSP) as the limited number of cases precludes the extrapolation of results. In our center we successfully use two-step treatment with methotrexate (MTX) followed by hysteroscopic removal of products of conception (POC). The time in between is needed to achieve a decrease in the trophoblast's vital potential (B-hCG fall) and its vascularization. Additional administration of letrozole could further reduce the vital potential of the pregnancy, eliminating the need for another dose of MTX, resulting in faster healing and lower rate of complications.

A prospective cohort study is conducted among women with cesarean scar pregnancy (CSP). Women with increasing B-human chorionic gonadotropin (B-hCG) concentrations are included.

Two study arms were planned:

* women treated with a single dose of 100 mg MTX intravenously and 50 mg MTX in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH)
* women treated with a single dose of 100 mg MTX intravenously and 50 mg MTX in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH) with additional use of letrozole 5 mg orally (from day 0) for 10 days.

Blood parameters (B-hCG, hemoglobin, total blood count, creatinine, urea, alanine/aspartate transaminase, gamma-glutamyltransferase, bilirubin) were tested on days 0,4,7, followed by B-hCG concentration measurement every 7 days until surgery. After obtaining satisfactory decrease in B-hCG and POC vascularization, women underwent hysteroscopic evacuation of POC. Blood loss parameters, frequency of conversion from hysteroscopy to laparoscopy and laparotomy were measured.

The women were given the option to choose the treatment used in the study. All enrolled women gave informed written consent to participate in the study.

Eligibility Criteria:
Inclusion Criteria:

* CSP confirmed on pelvic ultrasound
* consent of the Bioethics Committee for termination of CSP
* increasing B-hCG concentrations

Exclusion Criteria:

* heterotopic pregnancy
* decreasing B-hCG concentrations
Hypotension Decision Assist - Use, Safety and Efficacy

This clinical investigation will investigate whether Hypotension Decision Assist (HDA) is a feasible, safe and effective patient clinical decision support system to enhance an anaesthetist's ability to manage a patient's cardiovascular system when undergoing surgery. If successful, this study will provide evidence that the use of HDA facilitates beneficial outcomes for patients who have this device used.

In this study participants who are due to undergo elective major surgery and have an arterial line as part of their standard care will be invited to have the additional monitoring device (HDA) included as part of their care. Agreeing participants will have demographic, contact and medical history information necessary to conduct the study recorded, including a record of their intraoperative arterial line measurements.

After completing the consent process participants will receive intraoperative monitoring with Hypotension Decision Assist in addition to their standard care. The HDA monitor will be attached to the patient vital signs monitor, which will in turn be attached to the blood pressure transducer. All sampled arterial line data collected by the patient vital signs monitored will be automatically transmitted in real time to the HDA device via a serial cable attached to a digital export port of the vital signs monitor. HDA will process this input data to display, in graphical and numeric format, vital signs data and physiological parameters derived from the arterial wave form data including: Mean Arterial Pressure (MAP), systolic and diastolic blood pressure, heart rate and changes in heart rate, cardiac output and systemic vascular resistance.

The output from the study will be compared to the primary and secondary outcomes to evaluate the performance and safety of the device and to evaluate whether HDA improves control of the cardiovascular system from the anaesthetists' perspective.

Eligibility Criteria:
Inclusion Criteria:

* Adults (≥18 years) due to undergo elective surgery who are likely to have an arterial line sited as part of their standard intraoperative care.
* Recruitment after booking for surgery with sufficient time to read, understand and question study patient information prior to attending for surgery.
* Ability and willingness to provide informed consent
* Expected duration of anaesthesia \> 60 minutes
* Intra-arterial monitoring is part of routine clinical care

Exclusion Criteria:

* Inability to provide informed consent
* No arterial line planned as part of their intraoperative care
* Aged \< 18 years of age
* Patients with aortic regurgitation
* Patients fitted with an intra-aortic balloon pump (IABP)
* No other intra-arterial pressure management system in use
* Concurrent participation in another experimental intervention or drug study
Safety and Efficacy Study of Botulinum Toxin for the Treatment of Glabellar Frown Lines

The primary objective of the study is to evaluate the efficacy in wrinkle reduction of a single treatment of three different doses of botulinum toxin compared to placebo, in the treatment of moderate to very severe glabellar frown lines.


Eligibility Criteria:
Inclusion Criteria:

* Moderate to Very Severe glabellar lines at maximum frown as assessed by the subject and the Investigator and at least Mild glabellar lines at rest

Exclusion Criteria:

* Any previous treatment with any botulinum toxin
* Rhytids of the glabellar region that cannot be smoothed out by manually spreading the skin apart
* Any previous insertion of any permanent or semi-permanent material, hyaluronic acid or collagen fillers to the glabellar region
* Any history of facial surgery above the lower orbital rim
* Any planned facial surgery or aesthetic procedure during the study period
* Ablative skin resurfacing or chemical peels above the lower orbital rim in the previous 12 months or during the study period
Brown Seaweeds Effect on Glucose Tolerance and Appetite Response

The project is a randomized, 3-way, blinded crossover trial in which 20 healthy, fasted participants consume meals with 30 g of a linear corn starch and 5 g of one of the seaweeds, Laminara digitata or Undaria pinnatifida or a pea protein control. The primary aim is to investigate whether the brown seaweeds affect the postprandial glucose Area Under the Curve (AUC). Stomach emptying, insulin, C-peptide, appetite-regulating hormones (oxyntomodulin, glucagon, GLP-1 and PYY), and specific metabolites from the seaweeds in the urine and plasma as well as subjective satiety are also analyzed.

Brown seaweeds may contain bioactive compounds as they contain secondary plant metabolites, including flavonoids and other phenolic compounds as well as carotenoids. Dietary fibre is the major component of brown seaweeds, mainly composed from laminarans, alginates, fucans and cellulose. Several dietary fibers and secondary plant metabolites have been shown to have an impact on health and more specifically on glycemic control. Therefore, the aim of this study was to investigate whether two selected brown seaweeds have an effect on the postprandial glucose response to a starch load as well as several secondary measures, including appetite responses.

In a controlled crossover trial, 20 healthy fasted participants consumed 5 g of either Laminaria digitata (LD) or Undaria pinnatifida (UP) or 1 g of pea protein (CTR). The volunteers concomitantly ingested 200 mL of a drink with corn starch. Blood samples were drawn at baseline, as well as 20, 40, 60, 90, 120 and 180 min after the meal. Differences in glucose, insulin, C-peptide, plasma incretin concentrations, and insulin sensitivity index (ISI) were analyzed and appetite was scored by a visual analogue scale and a subsequent ad libitum test meal.

Eligibility Criteria:
Inclusion Criteria:

BMI 20-25 kg/m2. Waist circumference \< 102 cm. Non-smoking. Like (can tolerate) seaweed, pasta, meat sauce as these foods are part of the test meal.

Can tolerate paracetamol (Pinex, Actavis, Denmark).

Exclusion Criteria:

Systemic infections, psychiatric or metabolic diseases, and any clinical condition, chronic or frequent use of medication (including blood thinners, excluding contraceptives), smoking (throughout the trial and 12 months before the start of the experiment), blood donations during or in the month leading up to the study period, elite athletes (\> 10 hours of hard exercise / week, self-reported), high intake of alcohol (defined as a weekly intake of \> 7 units for women and \> 14 units for men), have or have had a drug addiction, participation in other scientific studies during the study period, lactating, pregnancy or ongoing planning of pregnancy, and vegetarianism or veganism.
TORPEDO Study: A Study on Rapid Effect of Tocilizumab in Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) or Anti-TNF

This study will assess the onset and maintenance of effect of tocilizumab on relief in patients with active moderate or severe rheumatoid arthritis who have had an inadequate response to DMARDs or anti-TNF. For the first, double-blind, part of the study patients will be randomized to receive an iv infusion of either 8mg/kg tocilizumab or placebo. After 4 weeks this will be followed by 11 months treatment with tocilizumab 8mg/kg iv infusion every 4 weeks. Methotrexate or DMARD therapy will be continued throughout study treatment. Target sample size is \>100.


Eligibility Criteria:
Inclusion Criteria:

* adult patients \>/= 18 years of age
* active moderate or severe rheumatoid arthritis of \<10 years duration with inadequate response to methotrexate or anti-TNF
* on methotrexate treatment for at least 10 weeks, at least 8 weeks on stable dose
* patients receiving oral corticosteroids and/or NSAIDs should be at stable dose for 4 weeks

Exclusion Criteria:

* rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
* functional class IV by ACR classification
* history of inflammatory joint disease other than RA
* previous treatment with cell-depleting therapies, abatacept or rituximab
* active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with iv antibiotics \<4 weeks or oral antibiotics \<2 weeks prior to screening
Managed Access Programs for PKC412, Midostaurin

The purpose of this registration is to list Managed Access Programs (MAPs) related to PKC4, Midostaurin.

* CPKC412A2001X - No longer available- An open-labeled, multi-center, Expanded Treatment Protocol (ETP) of midostaurin (PKC412) in patients 18 years of age or older with newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard induction and consolidation chemotherapy
* CPKC412AUS56X - No longer available - An open-label, multi-center, Expanded Treatment Protocol of Midostaurin (PKC412) in adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation chemotherapy.
* CPKC412A2407I - No longer available- Managed Access Program (MAP) Cohort Treatment Plan CPKC412A2407I to provide access to midostaurin (PKC412) for patients 18 years of age and older with newly-diagnosed FLT3-mutated AML and eligible for induction and consolidation chemotherapy
* CPKC412D2001M - No longer available- Managed Access Program (MAP) to provide access to Midostaurin (PKC412), for an individual patient with aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL) or mast cell sarcoma (MCS)

Eligibility Criteria:
Inclusion Criteria:

* An independent request should be received from a licensed physician (in some instances from Health Authorities, Institutions or Governments).
* The patient has a serious or life-threatening disease or condition and no comparable or satisfactory alternative therapy is available for diagnosis, monitoring or treatment; patient is not medically eligible for available treatment alternatives or has exhausted all available treatment options.
* The patient is not eligible or able to enroll in a Novartis clinical trial or continue participation in a Novartis clinical trial.
* There is a potential patient benefit to justify the potential risk of the treatment use, and the potential risk is not unreasonable in the context of the disease or condition to be treated.
* The patient must meet any other medical criteria established by the medical experts responsible for the product or by the Health Authority in a country (as applicable).
* Provision of the product will not interfere with the initiation, conduct or completion of a Novartis clinical trial or overall development program.
* Managed access provision is allowed per local laws/regulations.