Clinical trial NCT04324047: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients
Official title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Corona Virus Infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-03-27
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All adult patients with laboratory-confirmed SARS-CoV-2 infection

Brief summary: The overall objective of the study is to determine which treatments (e.g. immune modulator drugs) have the most favorable benefit-risk in adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation.

The specific aims of this Covid19 cohort are to collect observational data at regular intervals on an ongoing basis in order to embed a series of randomized controlled trials evaluating a various set of interventions for patients with COVID-19 pneumonia. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design.


Eligibility criteria: Inclusion Criteria:

* Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen \< 72 hours and/or CT Scan prior to randomization (Following typical radiological findings (ground glass abnormalities, and absence of lymphadenopathy, pleural effusion, pulmonary nodules, lung cavitation)
* Hospitalized patients
* Illness of any duration and severity (mild, moderate, severe, critical, see annexe 1), with symptoms (fever, cough, respiratory difficulties, shortness of breath), and at least one of the following:
* Radiographic infiltrates by imaging (CT scan)
* Clinical assessment (evidence of rales/crackles on exam or respiratory rate \>25/min) AND SpO2≤94% on room air
* SpO2≤97 % with O2 \> 5L/min or Respiratory rate\>=30/min
* Requiring mechanical ventilation
* With any comorbidities (TBD such as acute kidney injury, cardiovascular condition, pulmonary disease, obesity, high blood pressure, diabetes, chronic kidney diseases, haematological diseases, sickle cell diseases, autoimmune and auto-inflammatory, pregnant women, HIV infected, etc)
* Male or female adult ≥ 18 years of age at time of enrolment
* Patients must be able and willing to comply with study visits and procedures.
* Patient agrees to the collection of oropharyngeal and nasal swabs and venous blood per protocol Written informed consent provided by the patient or alternatively by next-of-kin prior to any protocol-specific procedures.

Exclusion Criteria:

* Patients with any condition that the physician judges could be detrimental to the patient participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical conditions (active infection diseases such as severe bacterial infections, aspergillosis, tuberculosis, depending on the tested medication).
* Absence of Health Insurance
* Subject protected by law under guardianship or curatorship

Primary outcomes:
measure: Survival
timeFrame: 14 days
measure: WHO progression scale COVID 19
timeFrame: 14 days
Secondary outcomes:
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: Kremlin Bictre APHP
state: Ile De France
city: Paris
country: France
facility: Cochin Aphp
state: Ile De France
city: Paris
country: France
facility: Hegp Aphp
state: Ile De France
Study officials:
References:
citation: Dal-Re R. COVID-19 drug research and the cohort multiple randomised controlled trial design. Eur Respir J. 2022 Sep 15;60(3):2200746. doi: 10.1183/13993003.00746-2022. Print 2022 Sep.
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.