Corona Virus Infection
Conditions
Brief summary
The overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the CORIMUNO-19 cohort. Anakinra will be administered to consenting adult patients hospitalized with CORVID-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 Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
Interventions
DRUGAnakinra
Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 with C-reactive protein level (CRP) \> 25 mg / L the day or the day before the infusion) 3. Patients belonging to one of the 2 following groups: * Group 1: patients meeting all of the following criteria: 1) Requiring more than 3L/min of oxygen; 2) WHO progression scale = 5; 3) No non invasive ventilation or High flow * Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR non invasive ventilation OR High flow), with a WHO progression scale ≥ 6, and no do-not-resuscitate (DNR) order
Exclusion criteria
* Patients with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- Severe COVID Population (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 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. |
| 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 (percentage) 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. |
| Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5) | 4 days | Percentage of patients with a decrease of WHO score of at least 1 point at day 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | 28 and 90 days | Time to oxygen supply independency |
| WHO Clinical Progression Scale | 4, 7, 14, 28 days | WHO clinical 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 Non invasive Ventilation 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 (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | 28 and 90 days | Time to discharge from Intensive Care Unit |
| Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | 28 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 |
| 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 |
| PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | day 1 to day 14 | Evolution of PaO2/FiO2 ratio |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5).
In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
Anakinra: Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5).
In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter | 59 |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) Usual care was provided at the discretion of the site clinicians | 55 |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5).
In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter Anakinra: Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5).
In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter | 22 |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) Usual care was provided at the discretion of the site clinicians | 20 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrew consent | 0 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Standard of Care -- Severe COVID Population (WHO-CPS =5) | ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67 years | 64.9 years | 59.6 years | 61.5 years | 64.7 years |
| Body Mass Index >= 30 kg/m² | 13 Participants | 15 Participants | 7 Participants | 8 Participants | 43 Participants |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Respiratory rate | 28 breaths/min | 28 breaths/min | 30 breaths/min | 26 breaths/min | 28 breaths/min |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 7 Participants | 5 Participants | 46 Participants |
| Sex: Female, Male Male | 43 Participants | 37 Participants | 15 Participants | 15 Participants | 110 Participants |
| SPO2 | 95 % | 95 % | 94.5 % | 94.5 % | 95 % |
| Temperature | 37.8 °C | 37.6 °C | 37.8 °C | 38.3 °C | 37.8 °C |
| Weight | 78 kg | 77.5 kg | 81 kg | 85 kg | 80 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 | 16 / 59 | 16 / 55 | 6 / 22 | 4 / 20 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 27 / 59 | 21 / 55 | 14 / 22 | 9 / 20 |
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 (percentage) 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 clinical progression scale \>5 at baseline)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ANAKINRA -- 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) | 50 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) | 40 percentage of participants |
90% CI: [0.59, 2.81]Bayesian Fine and Gray analysis
Primary
Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5)
Percentage of patients with a decrease of WHO score of at least 1 point at day 4
Time frame: 4 days
Population: Critical COVID population (WHO clinical progression scale \>5)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5) | 36 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5) | 10 percentage of participants |
90% CI: [3.9, 43.5]Bayesian analysis
Primary
Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- Severe COVID Population (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 clinical progression scale =5 at baseline)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline) | 47 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 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline) | 51 percentage of participants |
90% CI: [0.62, 1.52]Bayesian Cox model
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.
Time frame: 4 days
Population: Severe COVID population (WHO clinical progression scale =5 at baseline)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ANAKINRA -- 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) | 36 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) | 38 percentage of participants |
90% CI: [-17.1, 12]Bayesian analysis
Secondary
Cumulative Incidence (Percentage of Participants) of Discharge From Hospital
Time to discharge from hospital
Time frame: 28 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 58 percentage of participants |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | NA percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | NA percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 62 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | 68 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 41 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 28 | 40 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Day 90 | 65 percentage of participants |
95% CI: [0.56, 1.48]Fine-Gray model
95% CI: [0.35, 2.34]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 and 90 days
Population: Patients in the intensive care unit at inclusion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ANAKINRA -- 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 | 65 percentage of participants |
| ANAKINRA -- 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 | 88 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 | 65 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: [0.43, 2.32]Fine-Gray model
Comparison: Day 9095% CI: [0.52, 2.29]Fine-Gray model
Secondary
Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency
Time to oxygen supply independency
Time frame: 28 and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 63 percentage of participants |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | NA percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | NA percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 69 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 59 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | 77 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 28 | 50 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Day 90 | 70 percentage of participants |
95% CI: [0.64, 1.61]Fine-Gray model
95% CI: [0.58, 3.07]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 clinical progression scale \>5 at baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) | 14.4 days | Standard Deviation 11.9 |
| 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) | 14.8 days | Standard Deviation 12.6 |
95% CI: [-8.3, 6.4]
Secondary
PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
Evolution of PaO2/FiO2 ratio
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) |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 1 | 175.0 mmHg |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 4 | 114.5 mmHg |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 7 | 182.0 mmHg |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 14 | 180.0 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 14 | 218.3 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 1 | 118.7 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 7 | 142.0 mmHg |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Day 4 | 136.1 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) |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 85 percentage of participants |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 72 percentage of participants |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 78 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 76 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 72 percentage of participants |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 76 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 96 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 91 percentage of participants |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 73 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 14 | 85 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 90 | 80 percentage of participants |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | Percentage of Participants Surviving (Overall Survival) | Day 28 | 85 percentage of participants |
Comparison: 14 days95% CI: [0.23, 1.29]Regression, Cox
Comparison: 28 days95% CI: [0.33, 1.77]Regression, Cox
95% CI: [0.46, 2.04]Regression, Cox
95% CI: [0.11, 3.86]Regression, Cox
95% CI: [0.19, 4.68]Regression, Cox
95% CI: [0.31, 4.87]Regression, Cox
Secondary
WHO Clinical Progression Scale
WHO clinical 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 Non invasive Ventilation 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, 14, 28 days
Population: No comparison was planned at Day 7 in the Severe COVID Population (WHO clinical progression scale =5) so no descriptive/comparative data were done. No comparison was planned at Day 28 in Critical COVID Population (WHO clinical progression scale \>5) so no descriptive/comparative data were done.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 4 | 5 units on a scale |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 7 | NA units on a scale |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 14 | 5 units on a scale |
| ANAKINRA -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 28 | 5 units on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 7 | NA units on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 14 | 5 units on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 28 | 5 units on a scale |
| Standard of Care -- Severe COVID Population (WHO-CPS =5) | WHO Clinical Progression Scale | Day 4 | 5 units on a scale |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 14 | 6 units on a scale |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 7 | 7 units on a scale |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 28 | NA units on a scale |
| ANAKINRA -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 4 | 7 units on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 28 | NA units on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 7 | 7 units on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 4 | 6 units on a scale |
| Standard of Care -- Critical COVID Population (WHO-CPS >5) | WHO Clinical Progression Scale | Day 14 | 6 units on a scale |
Comparison: Day 495% CI: [0.38, 1.68]Bayesian Proportionnal odds model
Comparison: Day 1495% CI: [0.33, 1.43]Bayesian Proportionnal odds model
Comparison: Day 2895% CI: [0.35, 1.38]Bayesian Proportionnal odds model
Comparison: Day 495% CI: [0.22, 2.39]Bayesian Proportionnal odds model
Comparison: Day 795% CI: [0.28, 2.8]Bayesian Proportionnal odds model
95% CI: [0.18, 1.75]Bayesian Proportionnal odds model