Corona Virus Infection
Conditions
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.
Interventions
DRUGSarilumab
(an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Bayesian open labelled randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline) | 4 days | Percentage of participants who has died or needed non-invasive or mechanical ventilation by day 4 (WHO clinical progression scale \> 5). A patient with new do-not-resuscitate 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 |
| Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline) | Day 1 to Day 14 | Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Percentage of non-invasive ventilation, mechanical ventilation or death. Thus, events considered are needing ventilator utilization (mechanical or non-invasive ventilation including high flow oxygen), or death. New do-not-resuscitate (DNR) order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR. |
| Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline) | 4 days | Results are presented as the percentage not improved, so that an effective treatment would be associated with a decrease in percentage 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 |
| Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 1 to 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 Non Invasive Ventilation or high flow (for \> 48h) if they were included under oxygen by Non Invasive Ventilation or High flow (score 6) and remained without intubation. Death or new do-not-resuscitate order (if given after the inclusion of the patient) will be considered as a competing event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | 28, 90 days | Time to discharge from hospital |
| Percentage of Participants Surviving (Overall Survival) | 14, 28 and 90 days | Percentage of participants surviving at 14, 28 and 90 days |
| PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | day 1 to day 14 | evolution of PaO2/FiO2 ratio PaO2 is partial pressure of arterial oxygen expressed in mmHg. FiO2 is fraction of inspired oxygen (for instance, 0.33 for 33% oxygen) with no units. PaO2/FiO2 ratio is expressed in mmHg. |
| Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | 28, 90 days | Time to discharge from Intensive Care Unit |
| WHO Progression Scale | 4, 7 and 14 days | 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 |
| Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) | 28 days | 28-day ventilator free-days |
| Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | 28, 90 days | Time to oxygen supply independency |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at Day 1). Administration of Sarilumab fixed dose on day 3 was recommended and left to the treating physician | 68 |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) Usual care was provided at the discretion of the clinicians | 76 |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at Day 1). Administration of Sarilumab fixed dose on day 3 was recommended and left to the treating physician | 48 |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) Usual care was provided at the discretion of the clinicians | 33 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | withdrew consent | 0 | 4 | 2 | 8 |
Baseline characteristics
| Characteristic | SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Standard of Care -- Severe COVID Population (WHO-CPS =5) | SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.7 years | 62.8 years | 61.9 years | 61.2 years | 62.2 years |
| Body Mass Index >= 30 kg/m² | 14 Participants | 17 Participants | 18 Participants | 9 Participants | 58 Participants |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 12 Participants | 7 Participants | 55 Participants |
| Sex: Female, Male Male | 49 Participants | 59 Participants | 36 Participants | 26 Participants | 170 Participants |
| SPO2 | 94 % | 95 % | 94 % | 92 % | 95 % |
| Temperature | 37.9 °C | 37.7 °C | 37.7 °C | 37.7 °C | 37.7 °C |
| Weight | 81.5 kg | 85 kg | 83.5 kg | 83.5 kg | 82.5 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 68 | 16 / 76 | 14 / 48 | 13 / 33 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 27 / 68 | 28 / 76 | 31 / 48 | 19 / 33 |
Outcome results
Primary
Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
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 Non Invasive Ventilation or high flow (for \> 48h) if they were included under oxygen by Non Invasive Ventilation or High flow (score 6) and remained without intubation. Death or new do-not-resuscitate order (if given after the inclusion of the patient) will be considered as a competing event.
Time frame: Day 1 to Day 14
Population: Critical COVID Population (WHO-CPS \>5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | 38 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | 33 percentage of participants |
90% CI: [0.55, 2.07]Bayesian analysis
Primary
Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline)
Results are presented as the percentage not improved, so that an effective treatment would be associated with a decrease in percentage 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
Population: Critical COVID Population (WHO-CPS \>5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline) | 71 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline) | 79 percentage of participants |
90% CI: [-22.5, 8.7]Bayesian analysis
Primary
Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline)
Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Percentage of non-invasive ventilation, mechanical ventilation or death. Thus, events considered are needing ventilator utilization (mechanical or non-invasive ventilation including high flow oxygen), or death. New do-not-resuscitate (DNR) order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Time frame: Day 1 to Day 14
Population: Severe COVID population (WHO-CPS =5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline) | 37 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline) | 34 percentage of participants |
90% CI: [0.69, 1.74]Bayesian analysis
Primary
Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
Percentage of participants who has died or needed non-invasive or mechanical ventilation by day 4 (WHO clinical progression scale \> 5). A patient with new do-not-resuscitate 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
Population: Severe COVID Population (WHO-CPS =5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline) | 26 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline) | 26 percentage of participants |
90% CI: [-11.7, 12.2]Bayesian analysis
Secondary
Cumulative Incidence (Percentage of Participants) of Discharge From Hospital
Time to discharge from hospital
Time frame: 28, 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 75 percentage of participants |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | 79 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | 76 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 70 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 35 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | 65 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 30 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | 52 percentage of participants |
Comparison: Day 2895% CI: [0.81, 1.75]Fine-Gray model
Comparison: Day 9095% CI: [0.8, 1.67]Fine-Gray model
Comparison: Day 2895% CI: [0.55, 2.66]Fine-Gray model
Comparison: Day 9095% CI: [0.71, 2.37]Fine-Gray model
Secondary
Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
Time to discharge from Intensive Care Unit
Time frame: 28, 90 days
Population: Critical COVID Population (WHO-CPS \>5) Patients in the ICU at inclusion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 28 | 60 percentage of participants |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 90 | 79 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 28 | 71 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 90 | 82 percentage of participants |
Comparison: Day 2895% CI: [0.42, 1.44]Fine-Gray model
Comparison: Day 9095% CI: [0.49, 1.47]Fine-Gray model
Secondary
Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency
Time to oxygen supply independency
Time frame: 28, 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 75 percentage of participants |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | 81 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | 78 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 71 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 44 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | 71 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 36 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | 56 percentage of participants |
Comparison: Day 2895% CI: [0.72, 1.57]Fine-Gray model
Comparison: Day 9095% CI: [0.74, 2.25]Fine-Gray model
Comparison: Day 2895% CI: [0.59, 2.44]Fine-Gray model
Comparison: Day 9095% CI: [0.74, 1.55]Fine-Gray model
Secondary
Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)
28-day ventilator free-days
Time frame: 28 days
Population: Critical COVID Population (WHO-CPS \>5)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) | 10.3 days | Standard Deviation 11.1 |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) | 8.7 days | Standard Deviation 11 |
95% CI: [-6.1, 3.9]
Secondary
PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5)
evolution of PaO2/FiO2 ratio PaO2 is partial pressure of arterial oxygen expressed in mmHg. FiO2 is fraction of inspired oxygen (for instance, 0.33 for 33% oxygen) with no units. PaO2/FiO2 ratio is expressed in mmHg.
Time frame: day 1 to day 14
Population: No statistical comparison was performed due to the limited number of patients with available follow-up data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 7 | 142.4 mmHg |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 1 | 177.8 mmHg |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 14 | 139.8 mmHg |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 4 | 143.0 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 14 | 212.0 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 7 | 157.0 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 4 | 156.4 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5) | Day 1 | 106.4 mmHg |
Secondary
Percentage of Participants Surviving (Overall Survival)
Percentage of participants surviving at 14, 28 and 90 days
Time frame: 14, 28 and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 91 percentage of participants |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 85 percentage of participants |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 88 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 89 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 79 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 82 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 71 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 75 percentage of participants |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 71 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 73 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 61 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 67 percentage of participants |
95% CI: [0.23, 2.03]Regression, Cox
Comparison: Day 2895% CI: [0.27, 1.59]Regression, Cox
Comparison: Day 9095% CI: [0.31, 1.58]Regression, Cox
Comparison: Day 1495% CI: [0.4, 2.25]Regression, Cox
Comparison: Day 2895% CI: [0.4, 1.96]Regression, Cox
Comparison: Day 9095% CI: [0.35, 1.58]Regression, Cox
Secondary
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
Time frame: 4, 7 and 14 days
Population: Missing data are possible
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | WHO Progression Scale | 4 | 5 score on a scale |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | WHO Progression Scale | 14 | 4 score on a scale |
| SARILUMAB -- Severe COVID Population (WHO-CPS =5) | WHO Progression Scale | 7 | 5 score on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Progression Scale | 4 | 5 score on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Progression Scale | 14 | 5 score on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Progression Scale | 7 | 5 score on a scale |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | WHO Progression Scale | 7 | 8 score on a scale |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | WHO Progression Scale | 4 | 7 score on a scale |
| SARILUMAB -- Critical COVID Population (WHO-CPS >5) | WHO Progression Scale | 14 | 7 score on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Progression Scale | 4 | 8 score on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Progression Scale | 14 | 7 score on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Progression Scale | 7 | 8 score on a scale |
Comparison: Day 495% CI: [0.53, 2.34]Proportionnal odds model
Comparison: Day 795% CI: [0.49, 2.08]Proportionnal odds model
Comparison: Day 1495% CI: [0.42, 1.47]Proportionnal odds model
Comparison: Day 495% CI: [0.38, 2.02]Proportionnal odds model
Comparison: Day 1495% CI: [0.47, 2.4]Proportionnal odds model
Comparison: Day 9095% CI: [0.5, 2.57]Proportionnal odds model