Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI
Latest Information Update: 07 Mar 2022
At a glance
- Drugs Sarilumab (Primary)
- Indications COVID 2019 infections; Pneumonia
- Focus Therapeutic Use
- Acronyms CORIMUNO-19-SARI; CORIMUNO-SARI; SARI-2
- 03 Feb 2022 Results of TOCI-2 trial and SARI-2 study analysis published in the European Respiratory Journal
- 14 Apr 2020 Status changed from recruiting to active, no longer recruiting.
- 31 Mar 2020 Planned number of patients changed from 180 to 240.
Most Recent Events
Trial Overview
Purpose
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.
Primary Endpoints
Survival without needs of ventilator utilization at day 14.
description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
time_frame: 14 days
WHO progression scale ≤5 at day 4
description: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5.
WHO progression scale:
Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2≥150 OR SpO2/FIO2≥200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
time_frame: 4 days
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14
description: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
time_frame: 14 days
WHO progression scale at day 4
description: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Scale:
Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2≥150 OR SpO2/FIO2≥200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9
time_frame: 4 days
Other Endpoints
WHO progression scale
description: WHO progression scale:
Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2≥150 OR SpO2/FIO2≥200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
time_frame: 7 and 14 days
Survival
description: Overall survival
time_frame: 14, 28 and 90 days
28-day ventilator free-days
time_frame: 28 days
respiratory acidosis at day 4
description: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
time_frame: 4 days
PaO2/FiO2 ratio
description: evolution of PaO2/FiO2 ratio
time_frame: day 1 to day 14
time to oxygen supply independency
description: time to oxygen supply independency
time_frame: 14 days
duration of hospitalization
description: duration of hospitalization
time_frame: 90 days
time to negative viral excretion
description: time to negative viral excretion
time_frame: 90 days
time to ICU discharge
description: time to ICU discharge
time_frame: 90 days
time to hospital discharge
description: time to hospital discharge
time_frame: 90 days [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID 2019 infections | treatment | - |
| Pneumonia | treatment | moderate, severe |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04324073 | IQ motif containing GTPase activating protein 1 | Brief Title, Official Title |
| secretion associated Ras related GTPase 1A | Brief Title, Official Title |
Subjects
- Subject Type patients
-
Number
Planned: 240
Actual: 239
- Sex male & female
- Age Group ≥ 18 years; adult
Patient 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 ICU 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 ICU based on Criteria of severity of COVID pneumopathy. - Respiratory failure and requiring mechanical ventilation - No do-not-resuscitate order (DNR order)
Patient 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
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04324073 | ClinicalTrials.gov: US National Institutes of Health |
| APHP200375-2 | - |
Trial Dates
-
Initiation Dates
Planned : 26 Mar 2020
Actual : 27 Mar 2020
-
Primary Completion Dates
Planned : 27 Mar 2021
-
End Dates
Planned : 31 Dec 2021
Other Details
- Design multicentre; open; parallel; prospective; randomised
- Phase of Trial Phase II/III
- Location France
- Focus Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| SarilumabPrimary Drug | Intravenous | Infusion |
SARILUMAB
Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1).
Drug: Sarilumab ((an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1)
Standard of care
best standard of care
Results
Publications
-
Hermine O, Mariette X, Porcher R, Resche-Rigon M, Tharaux PL, Ravaud P. 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;.
PubMed | CrossRef Fulltext
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Matthieu RESCHE-RIGON, MD PhD
685740240 Ext: +33 matthieu.resche-rigon@u-paris.fr
show details
|
-
|
|
|
matthieu resche-rigon, MD-PhD
685740240 +33 matthieu.resche-rigon@u-paris.fr
show details
|
NECKER Hospital | France |
|
Olivier HERMINE, MD-PhD
603707920 Ext: +33 ohermine@gmail.com
show details
|
-
|
|
| Xavier Mariette, MD-PHD | Kremlin Bicetre hospital APHP | France |
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| - |
-
|
-
|
| Assistance Publique - Hôpitaux de Paris |
-
|
-
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| Cochin Aphp | Paris, Ile De France | France |
| HEGP | Paris, Ile De France | France |
| Kremlin Bicetre hospital APHP | Le Kremlin-Bicêtre, Ile De France | France |
| NECKER Hospital | Paris | France |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 07 Mar 2022 | Other trial event | According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified Mar 2020). Updated 07 Mar 2022 |
| 07 Mar 2022 | Other trial event | Last checked against the ClinicalTrials.gov record. Updated 07 Mar 2022 |
| 03 Feb 2022 | Results | Results of TOCI-2 trial and SARI-2 study analysis published in the European Respiratory Journal Updated 11 Feb 2022 |
| 15 Apr 2020 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
| 14 Apr 2020 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 16 Apr 2020 |
| 31 Mar 2020 | Other trial event | Planned number of patients changed from 180 to 240. Updated 03 Apr 2020 |
| 31 Mar 2020 | Other trial event | Planned primary completion date changed from 26 Mar 2021 to 27 Mar 2021. Updated 03 Apr 2020 |
| 31 Mar 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 03 Apr 2020 |
| 30 Mar 2020 | New trial record | New trial record Updated 30 Mar 2020 |
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Hermine O, Mariette X, Porcher R, Resche-Rigon M, Tharaux PL, Ravaud P. 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;.
PubMed | CrossRef Fulltext
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