cyrilzakka/clinical-trials huggingface dataset:
Study of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial - CORIMUNO-19 - VIRO

The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in combination with Azithromycin and Hydroxychloroquine, compared to Sarilumab only, patients with moderate, severe pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering investigational treatments administration to patients enrolled in the CORIMUNO-19 cohort (NCT04324047). Sarilumab+Azithromycin+Hydroxychloroquine, or Sarilumab only will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation. All patients will receive standard of care along with randomized investigational treatments. Outcomes of included patients will be compared between groups as well as with outcomes of patients in the CORIMUNO-19 cohort treated with other immune modulators or standard of care.


Eligibility Criteria:
Inclusion Criteria:

* Patients included in the CORIMUNO-19 cohort (NCT04324047)
* COVID-19 cases not requiring ICU at admission with moderate or severe pneumopathy according to the WHO Criteria of severity of COVID pneumopathy:

  * Moderate cases: Cases meeting all of the following criteria: \[Showing fever and respiratory symptoms with radiological findings of pneumonia\] AND \[Requiring between 3L/min and 5L/min of oxygen to maintain SpO2\>97%\] OR
  * Severe cases: Cases meeting any of the following criteria: \[Respiratory distress ( ≥ 30 breaths/ min)\] OR \[Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 \> 5L/min\] OR \[PaO2/FiO2 ≤ 300mmHg\]

Exclusion Criteria:

1. Patients with exclusion criteria to the CORIMUNO-19 cohort.
2. Respiratory failure requiring non invasive or mechanical ventilation
3. Patients requiring intensive care
4. Do-not-resuscitate order (DNR order)
5. Known hypersensitivity to sarilumab or to any of their excipients.
6. Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation
7. Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation
8. Pregnancy or breastfeeding
9. Current documented bacterial infection.
10. Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:

    * Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
    * Haemoglobin level: no limitation
    * Platelets (PLT) \< 50 G /L
    * SGOT or SGPT \> 5N
Smoking in the Paris Fire Brigade and Comparison According to the Type of Service (Permanent or On-call)

Tobacco use is one of the world's leading preventable causes of disease and premature death, and the physician has a central role in detecting smokers and helping them to quit.

Tobacco use in the military undermines fitness, readiness and performance, and increases health care costs.

A study conducted on a French Army contingent on external operations in Afghanistan have shown an increase in tobacco use in situation of operational constraints (stress, shift work, etc.). However, another study conducted in Ivory Coast on a mobile gendarmerie squadron showed no significant difference.

Among the American firefighters who have been exposed to the 9/11 World Trade Center attacks, smoking have been shown to play an aggravating role in the recovery of lung function.

This study is aimed at assessing smoking prevalence in the Paris Fire Brigade, which is composed of young and healthy sportsmen and women who are exposed to strong operational constraints.


Eligibility Criteria:
Inclusion Criteria:

* To be 18 years of age or older
* To be French
* To be an active military member
* To work in the Paris Fire Brigade

Exclusion Criteria:

* To be a civilian
* To be a reservist
* To be a foreigner
A Phase 1, Single- and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MEDI4166 in Subjects With Type 2 Diabetes

A Phase 1, combined Single Ascending Dose (SAD) and Multiple-ascending Dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MEDI4166 in Subjects with Type 2 Diabetes Mellitus (T2D).

This study is a first time in human (FTIH), Phase 1, randomized, double-blind study to evaluate the safety, tolerability, PK, and PD of MEDI4166 administered as both single and multiple ascending doses to subjects with T2D.

Eligibility Criteria:
Inclusion Criteria:

* Type 2 Diabetes, ages 18-65
* Must provide written informed consent
* BMI\>=25 and =\<42
* Venous access suitable for multiple cannulations
* Vital signs within normal specified ranges
* Females must be non-lactating and non-childbearing potential
* Males must practice 2 effective contraceptive measures if sexually active

Exclusion Criteria:

* Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
* History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* History of cancer, with the exception of basal cell carcinoma or carcinoma of the cervix
* Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
* Positive Hepatitis B, Hepatitis C or HIV test or use of antiretroviral medications at screening
* Current or previous use of systemic corticosteroids within the past 28 days prior to screening
* Use of any medicinal products or herbal preparations licensed for weight loss is prohibited.
* Positive drug screen
* Type 1 diabetes
Investigation of Autonomic Dysfunction in Patients With Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is the most common inherited autoinflammatory disease affecting 150,000 patients worldwide. Periodic febrile exacerbations, peritonitis, and pleuritis are characteristic disease features. Dysregulation of IL-1β secretion has an important role in the pathophysiology of the disease, and IL-1β also serves as a therapeutic target. Chronic inflammation has been associated with early atherosclerotic and cardiovascular disease in various rheumatic diseases. An increased risk for cardiovascular events associated with disease activity has been described in rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. In addition, autonomic nervous system dysfunction may contribute to increased cardiovascular risk in patients with inflammatory disease. For example, decreased heart rate variability is an important feature of cardiac autonomic dysfunction and is an isolated risk factor for cardiovascular events. Autonomic dysfunction studies related to FMF have conflicting results.

The aim of this study was to determine autonomic dysfunction symptoms and objective findings in patients with FMF; Demographic characteristics, disease characteristics, inflammatory burden, fatigue level, sleep quality, presence of fibromyalgia and their relationship with quality of life were evaluated and compared with healthy controls.


Eligibility Criteria:
Inclusion Criteria:

Familial Mediterranean Fever group;

1. Being between the ages of 18-65
2. Having a definite diagnosis of Familial Mediterranean Fever according to Livneh criteria

Healthy control group;

1. Being between the ages of 18-65
2. Absence of any disease diagnosis

Exclusion Criteria:

1. Liver or kidney failure
2. Pregnancy
3. Diabetes mellitus
4. Thyroid diseases
5. Those who use neuroprotective or antihypertensive drugs
6. Vitamin B12 deficiency
7. Anemia
8. Paraneoplastic neuropathy
9. Alcoholism
10. Cardiac failure
11. Cardiac arrhythmia
12. Acute thrombosis
13. Having a diagnosis of another systemic rheumatic disease
14. Persons who did not give consent to participate in the study
Antibiotic Exposure During Pregnancy Affects Infant Gut Microbiota

Based on a prospective birth cohort, the investigators will collect biological samples from participants including pregnant women and newborns, to measure the gut microbial diversity and metabolites of newborns. These results systematically evaluate the effects of antibiotic exposure on the structure and function of gut microbiota. The project can reveal the effects of antibiotic exposure on the growth and development of gut microbiota in early life.


Eligibility Criteria:
Inclusion Criteria:

1. Pregnant woman

   * aged 20-40 years old
   * natural conception
   * single pregnancy
   * gestational age ≥36 weeks
2. Newborn

   * normal Apgar score
   * no serious congenital diseases

Exclusion Criteria:

-
A Clinical Trial to Evaluate Drug-drug Interactions and Safety Between "BR1015-1" and "BR1015-2" in Healthy Volunteers

The purpose of this study is to evaluate pharmacokinetic interactions (Drug-Drug interaction) and safety between "BR1015-1" and "BR1015-2" in healthy volunteers.

\*Study Objective: After repeated administration of BR1015-1 and BR1015-2 for healthy volunteers, the pharmacokinetic interactions and safety are evaluated.

\*Investigational Product (and regimen)

1. BR1015-1: Administration of BR1015-1 60 mg once a day for 5 days
2. BR1015-2: Administration of BR1015-2 1.5 mg once a day for 5 days
3. BR1015-1+BR1015-2: Co-administration of BR1015-1 60 mg and BR1015-2 1.5 mg once a day for 5 days

Eligibility Criteria:
Inclusion Criteria:

* Subjects are given sufficient explanations about the trial objectives and contents as well as properties of investigational drugs before participating in the trial, and will voluntarily express their consent by signing an IRB-approved written consent to participate in the trial.
* Healthy adults aged 19 to 55 years at screening.
* The subject's weight is 50 kg or more for males, 45 kg or more for females, and body mass index (BMI) is 18.0 or more but 30.0 kg/m2 or less.

Exclusion Criteria:

* Those who have history of clinically significant diseases including hypersensitivity reaction, intolerability and anaphylaxis to major ingredients and other ingredients of investigational products.
* Those who have history of clinically significant diseases including allergy reaction to Yellow No. 5 (Sunset Yellow FCF).
* Those who have a history of clinically significant diseases related to liver, kidney, digestive system, respiratory system, musculoskeletal system, endocrine system, neuropsychiatric system, hemato-oncology system, cardiovascular system (including orthostatic hypotension), etc.
* Those who have medical history of gastrointestinal system diseases (for example: Crohn's disease, peptic ulcer disease, etc.) and operations that may influence the absorption of investigational drugs. (However, appendectomy, hernia operation, endoscopic polypectomy and hemorrhoids/anal fissure/anal fistula surgeries are excluded.)
* Those with abnormal findings from the screening tests (medical interview, vital signs, electrocardiography, physical checkup, blood test, urinalysis, etc.) are judged to have clinical significance.
* Those who are positive to HBsAg, HCV Ab, HIV Ab, VDRL tests at screening.
* Those with any of the following results at screening:
* AST or ALT \> twice the upper limit of normal range
* T. bilirubin \> twice the upper limit of normal range
* Estimated glomerular filtration rate (e-GFR) \< 60 mL/min/1.73m2 (CKD-EPI method used)
* Na \> 150 mEq/L or \<130 mEq/L
* K \> 5.5 mEq/L or \<3.0 mEq/L
* Those with systolic blood pressure \> 160 mmHg or \< 110 mmHg, or diastolic blood pressure \> 100 mmHg or \< 70 mmHg from vital signs at screening.
* Others who are judged to be ineligible to participate in the trial by the investigator.
Mycophenolate Mofetil Versus Intravenous Cyclophosphamide Pulses in the Treatment of Crescentic IgA Nephropathy

A single-center random parallel study to compare the efficacy and safety of Mycophenolate mofetil versus intravenous Cyclophosphamide pulses in the treatment of crescentic IgA nephropathy

IgA nephropathy is an immune-complex glomerulopathy that can result in capillary necrosis or extracapillary proliferation (crescents). Several studies have documented a higher incidence of hypertension and nephritic-range proteinuria in patients with the crescentic form of IgA nephropathy, suggesting that patients with this variant of the disease may have a worse prognosis. Some studies have shown that treatment with steroids and cyclophosphamide had efficacy on reducing proteinuria and preserving renal function by healing vasculitic lesions, therefore preventing the progression of glomerular sclerosis. Recent studies have also shown that mycophenolate mofetil is effective in the treatment of lupus nephritis with vasculitic lesion and small vasculitis with renal involvement. We will conduct a single-center prospective open-labeled clinical trial of 40 patients with crescentic IgA nephropathy and treat them randomly with pulse intravenous cyclophosphamide or oral mycophenolate mofetil. After 12 months of treatment, we will assess the efficacy, safety, tolerability and relapse of mycophenolate mofetil compared with cyclophosphamide in the treatment of crescentic IgA nephropathy.

Eligibility Criteria:
Inclusion Criteria:

Patient with a diagnosis of IgAN without deposition of C4 and C1q, age 10-70y, sex free

1. Gross hematuria or an active urine sediment
2. Segmental necrotizing lesion of the capillary wall
3. Cellular or fibrocellular crescents ≥ 10%
4. Fibrinoid degeneration of small vessels
5. Fibrin positive Three or more items, with provision of criteria informed consent

Exclusion Criteria:

1. More than four-week treatment with cytotoxic drug, such as CTX, CsA and MMF, prior to enrollment
2. Immune deficiency
3. Serum creatinine ≥ 5.0mg/dl
4. Previous malignancy
5. Pregnancy
6. Hepatitis
7. Diabetic mellitus or obesity
8. Severe infection or CVS complications
9. Henoch-Schonlein purpura nephritis, systemic vasculitis, SLE
Immunostimulating Interstitial Laser Thermotherapy in Breast Cancer

Thermotherapy is a technology aiming at destroying tissue, for example tumor tissue. Immunostimulating Interstitial Laser Thermotherapy (imILT) is a specific form of thermotherapy, which, in addition to destroying tumor tissue, has been optimized to cause a tumor specific immunologic response. In laboratory animals the imILT method has also been shown to induce a so called abscopal effect. This means that when one tumor is treated with imILT other, untreated, tumors also decrease in size. The immunologic response has previously been characterized in breast cancer patients after receiving imILT treatment , and presumed abscopal effects induced by imILT have also been described in a malignant melanoma patient.

The purpose of this trial is to investigate the functionality and safety of the imILT treatment method in patients diagnosed with breast cancer.

The treatment method has successfully been used for treatment of patients with breast cancer and malignant melanoma. Treatment of breast cancer patients caused an increase of cytotoxic T lymphocytes in the treated tumor, as well as activated dendritic cells at the tumor border. Regulatory T lymphocytes decreased in the regional lymph nodes.

This trial is explorative, prospective, open and non-randomized. Five breast cancer patients will be treated in this trial, which is estimated to be carried out during a time period of 9 months.


Eligibility Criteria:
Inclusion Criteria:

1. Have histologically confirmed breast cancer
2. Hormone receptor positive or negative
3. Have assessable tumour by MRI or ultrasound
4. Are patients deemed unfit for surgical excision of tumour under general anaesthetic.
5. Have been given informed verbal and written consent for participation in the trial
6. Have stable hematologic, renal and hepatic functions.

Exclusion Criteria:

1. Are known to be HIV positive
2. Have active autoimmune disease
3. Are on corticosteroid medication
4. Have evidence of bleeding diathesis or coagulopathy.
BUSCLAB - Buscopan to Prevent Slow Progress in Labor

To study the effect of Butylscopolamine Bromide on duration of the active phase of first stage of labor in first time mothers who cross the alert-line for labor dystocia, according to the WHO partograph.


Eligibility Criteria:
Inclusion Criteria:

* ≥18 years
* Primiparous women
* Spontaneous onset of labor
* Active phase of labor
* ≥37 weeks of gestation
* Vertex position
* Crossing the alert line, i.e. cervical dilatation of less than one cm per hour in the active phase of first stage of labour (cervix dilation ≥3 - \<10 cm)
* Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP and national and local regulations

Exclusion Criteria:

* Multiple gestation
* Elective cesarean section
* Women in labor already receiving oxytocin when crossing the alert line
* Fully dilated cervix when crossing the alert line
* Preeclampsia defined as blood pressure ≥140/90 and proteinuria (1 or more on a urine dipstick on more than one occasion) with debut after 20 weeks of pregnancy
* Known intestinal stenosis, ileus or megacolon
* Persisting maternal tachycardia (heart rate \>130 beats per minute)
* Known maternal myasthenia gravis
* Persisting fetal tachycardia (fetal heart rate baseline \>170 beats per minute)
* Hypersensitivity to any of the ingredients in IMP or placebo (butylscopolamine bromide or sodium chloride)
* Women with heart disease who are under surveillance with heart rate monitoring during labor
* Known fetal heart disease
* Untreated glaucoma
REVEAL-CKD: Prevalence and Consequences of Undiagnosed Chronic Kidney Disease

This is a retrospective, multinational, non-interventional, observational study. A series of cohort studies will be conducted to assess the prevalence of undiagnosed stage 3 CKD in each region. The study will also assess the current state of CKD management in patients with undiagnosed CKD

This study is a retrospective, multinational, non-interventional observational study. The study does not attempt to test any specific a priori hypothesis; it is descriptive only and will collect data under conditions of routine medical care. Relevant secondary databases will be identified, and a series of cohort studies will be conducted to assess the prevalence of undiagnosed CKD. The study will also assess the current state of CKD management in patients with undiagnosed CKD.

Primary Objectives

1. Estimate the point prevalence of undiagnosed stage 3 CKD (proportion of patients with eGFR measurements indicating stage 3 CKD with no corresponding CKD diagnostic code either before or up to six months after the second abnormal eGFR value)
2. Describe time to CKD diagnosis in patients with no prior CKD diagnosis code at index date (time of second qualifying eGFR), overall and by patient characteristics

Secondary Objectives

1. Assess trends in the prevalence (point prevalence) of undiagnosed CKD by calendar year
2. Describe baseline characteristics among those with undiagnosed versus diagnosed CKD
3. Assess CKD management and monitoring practices (post index date) in patients with diagnosed versus undiagnosed CKD

Exploratory objectives (pending feasibility)

1. Describe the risk of selected adverse clinical outcomes longitudinally among those with undiagnosed versus diagnosed CKD
2. Describe HCRU associated with undiagnosed versus diagnosed CKD
3. Assess association between the timing of the CKD diagnosis and the risk of selected adverse clinical outcomes and HCRU in patients with no CKD diagnosis code prior to the index date
4. Describe health care costs associated with undiagnosed versus diagnosed CKD
5. For CKD patients with eGFR 25-75 mL/min/1.73m2 and urine albumin creatinine ratio (UACR) 200 - 5000 mg/g (DAPA-CKD trial-like population):

   1. Estimate the point prevalence of undiagnosed CKD
   2. Describe the risk of selected adverse clinical outcomes longitudinally among those with undiagnosed CKD
   3. Describe HCRU and costs associated with undiagnosed CKD

Eligibility Criteria:
Inclusion Criteria:

* At least two consecutive eGFR laboratory tests with values ≥30 and \<60 mL/min/1.73 m2 (Stage 3A or 3B) that are \>90 and ≤730 days apart. The index date is the date of the second eGFR measure meeting the criteria for stage 3 CKD
* At least 12 months of continuous presence in the database or registration in the data prior to the first qualifying eGFR (for data sources with information on enrolment)
* Age ≥18 years at index date

Exclusion Criteria:

* Solid organ transplant before the study index date
* Any evidence of advanced CKD (stage 4, 5) based on CKD diagnostic codes, or renal replacement therapy before the index date
The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).

Life expectancy in CF patients has greatly increased due to improved clinical care. While this is certainly beneficial to CF patients, it has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 remains the primary outcome parameter for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2 %. Therefore, additional parameters are needed that are more sensitive to define abnormalities in CF patients and that can be used in therapeutic trials.

Gas mixing techniques have been shown to be sensitive parameters to define abnormalities in patients with cystic fibrosis, but it is unclear how useful this technique is to detect changes after a therapeutic intervention. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways and can be assessed with the lung clearance index (LCI). Interventions that improve mucous accumulation are expected to improve lung clearance as assessed by this technique. RhDNase has been demonstrated to improve lung function and reduce pulmonary exacerbations in patients with cystic fibrosis due to improved mucus clearance.

Lung clearance index (LCI) has been shown to be more sensitive than spirometry in detecting abnormalities in CF patients. Clear cut-offs have been found which can differentiate normal patients from even newly diagnosed CF patients. However, little is known about how LCI may change with treatment.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of CF as defined by clinical features of CF and a documented sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
* Informed consent and verbal assent (as appropriate) has been provided by the subject's parent or legal guardian and the subject
* 6-18 years of age at enrolment
* Able to perform reproducible spirometry
* Clinically stable at enrolment
* Ability to comply with medication use, study visits and study procedures as judged by the site investigator
* FEV1 % predicted \> 70 % as calculated by the Wang reference equations

Exclusion Criteria:

* Respiratory culture positive for:

  * NTM within past year or AFB positive at screening (sputum only)
  * B. cepacia complex within past year or at screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* Investigational drug use within 30 days of screening
* History of alcohol, illicit drug or medication abuse within 1 year of screening
* Other major organ dysfunction excluding pancreatic dysfunction
* History of lung transplantation or currently on lung transplant list
* Physical findings at screening that would compromise the safety of the participant or the quality of the study data