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Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI (CORIMUNO-SARI)

Primary Purpose

Corona Virus Infection

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Sarilumab
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

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

Sites / Locations

  • Kremlin Bicetre hospital APHP
  • Cochin Aphp
  • HEGP
  • NECKER Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

SARILUMAB

Standard of care

Arm Description

Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1).

best standard of care

Outcomes

Primary Outcome Measures

Survival without needs of ventilator utilization at day 14.
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.
WHO progression scale <=5 at day 4
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
Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14
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.
WHO progression scale at day 4
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

Secondary Outcome Measures

WHO progression scale
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
Survival
Overall survival
28-day ventilator free-days
respiratory acidosis at day 4
arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
PaO2/FiO2 ratio
evolution of PaO2/FiO2 ratio
time to oxygen supply independency
time to oxygen supply independency
duration of hospitalization
duration of hospitalization
time to negative viral excretion
time to negative viral excretion
time to ICU discharge
time to ICU discharge
time to hospital discharge
time to hospital discharge

Full Information

First Posted
March 25, 2020
Last Updated
April 14, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04324073
Brief Title
Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI
Acronym
CORIMUNO-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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 27, 2020 (Actual)
Primary Completion Date
March 27, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Bayesian open labelled randomized clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
239 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SARILUMAB
Arm Type
Experimental
Arm Description
Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1).
Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
best standard of care
Intervention Type
Drug
Intervention Name(s)
Sarilumab
Intervention Description
(an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1
Primary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Survival
Description
Overall survival
Time Frame
14, 28 and 90 days
Title
28-day ventilator free-days
Time Frame
28 days
Title
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
Title
PaO2/FiO2 ratio
Description
evolution of PaO2/FiO2 ratio
Time Frame
day 1 to day 14
Title
time to oxygen supply independency
Description
time to oxygen supply independency
Time Frame
14 days
Title
duration of hospitalization
Description
duration of hospitalization
Time Frame
90 days
Title
time to negative viral excretion
Description
time to negative viral excretion
Time Frame
90 days
Title
time to ICU discharge
Description
time to ICU discharge
Time Frame
90 days
Title
time to hospital discharge
Description
time to hospital discharge
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients included in the CORIMUNO-19 cohort 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) 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
Facility Information:
Facility Name
Kremlin Bicetre hospital APHP
City
Le Kremlin-Bicêtre
State/Province
Ile De France
Country
France
Facility Name
Cochin Aphp
City
Paris
State/Province
Ile De France
Country
France
Facility Name
HEGP
City
Paris
State/Province
Ile De France
Country
France
Facility Name
NECKER Hospital
City
Paris
ZIP/Postal Code
75005
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
34812424
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.
Results Reference
derived

Learn more about this trial

Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI

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