Clinical trial NCT04324073: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI
Official title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Corona Virus Infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-03-27
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Bayesian open labelled randomized clinical trial
Primary purpose: TREATMENT

Brief summary: The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in patients with moderate, severe pneumonia or critical 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 Sarilumab administration to patients enrolled in the CORIMUNO-19 cohort. Sarilumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Sarilumab will receive standard of care. Outcomes of Sarilumab-treated patients will be compared with outcomes of standard of care-treated patients as well as with outcomes of patients treated with other immune modulators.


Eligibility criteria: Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort
2. Patients belonging to one of the 2 following groups:

   * Group 1: patients not requiring Intensive Care Unit at admission with moderate and severe pneumopathy according to the OMS 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.
* Requiring between 3L/min and 5L/min of oxygen to maintain SpO2 \>97% Severe cases

Cases meeting any of the following criteria:

* Respiratory distress (≧30 breaths/ min);
* Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 \> 5L/min.
* PaO2/FiO2≦300mmHg
* Group 2: patients requiring Intensive Care Unit based on Criteria of severity of COVID pneumopathy.
* Respiratory failure and requiring mechanical ventilation
* No do-not-resuscitate order (DNR order)

Exclusion Criteria:

* Patients with exclusion criteria to the CORIMUNO-19 cohort.
* Known hypersensitivity to Sarilumab or to any of their excipients.
* Pregnancy
* Current documented bacterial infection
* 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

Primary outcomes:
measure: Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
timeFrame: 4 days
measure: Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline)
timeFrame: Day 1 to Day 14
measure: Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline)
timeFrame: 4 days
measure: Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: Day 1 to Day 14
Secondary outcomes:
measure: Percentage of Participants Surviving (Overall Survival)
timeFrame: 14, 28 and 90 days
measure: WHO Progression Scale
timeFrame: 4, 7 and 14 days
measure: Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)
timeFrame: 28 days
measure: Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency
timeFrame: 28, 90 days
measure: Cumulative Incidence (Percentage of Participants) of Discharge From Hospital
timeFrame: 28, 90 days
measure: Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: 28, 90 days
measure: PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5)
timeFrame: day 1 to day 14
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: Kremlin Bicetre hospital APHP
state: Ile De France
city: Paris
country: France
facility: Cochin Aphp
state: Ile De France
city: Paris
country: France
facility: HEGP
state: Ile De France
city: Paris
country: France
facility: NECKER Hospital
Study officials:
References:
citation: CORIMUNO-19 Collaborative group. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial. Lancet Rheumatol. 2022 Jan;4(1):e24-e32. doi: 10.1016/S2665-9913(21)00315-5. Epub 2021 Nov 17.
citation: Hermine O, Mariette X, Porcher R, Resche-Rigon M, Tharaux PL, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. Eur Respir J. 2022 Aug 10;60(2):2102523. doi: 10.1183/13993003.02523-2021. Print 2022 Aug.