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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ANAKINRA -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline) | Experimental | 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 |
|
| Standard of care -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline) | No Intervention | ||
| ANAKINRA -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline) | Experimental | 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 |
|
| Standard of care -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline) | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anakinra | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 to Day 14 |
| 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. | 4 days |
| 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. | Day 1 to Day 14 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Patients included in the CORIMUNO-19 cohort
Patients with C-reactive protein level (CRP) > 25 mg / L the day or the day before the infusion)
Patients belonging to one of the 2 following groups:
Exclusion Criteria:
Patients with exclusion criteria to the CORIMUNO-19 cohort.
Known hypersensitivity to Anakinra 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:
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| Name | Affiliation | Role |
|---|---|---|
| Xavier Mariette, MD, PhD | Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris | Le Kremlin-Bicêtre | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33493450 | Result | CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir Med. 2021 Mar;9(3):295-304. doi: 10.1016/S2213-2600(20)30556-7. Epub 2021 Jan 22. | |
| 38077399 | Derived | Joly C, Desjardins D, Porcher R, Pere H, Bruneau T, Zhang Q, Bastard P, Cobat A, Resmini L, Lenoir O, Savale L, Lecuroux C, Verstuyft C, Roque-Afonso AM, Veyer D, Baron G, Resche-Rigon M, Ravaud P, Casanova JL, Le Grand R, Hermine O, Tharaux PL, Mariette X. More rapid blood interferon alpha2 decline in fatal versus surviving COVID-19 patients. Front Immunol. 2023 Nov 21;14:1250214. doi: 10.3389/fimmu.2023.1250214. eCollection 2023. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the site clinicians |
| FG002 | 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 |
| FG003 | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Usual care was provided at the discretion of the site clinicians |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Severe COVID population ((WHO clinical progression scale =5 at baseline) | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 to Day 14 |
|
Adverse events were systematically assessed at Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14 while participants were inpatient, and at Days 28 and 60 and 90.
Only deaths and serious adverse events were reported. "0" total Number of Participants at Risk means " Other (Not Including Serious) Adverse Events were not monitored/analyzed ".
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute respiratory distress syndrom | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Raphael Porcher | Hopital Hotel-Dieu (AP-HP) | :+33 (0)1.42.34.89.87 | raphael.porcher@aphp.fr |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 14, 2020 | Apr 3, 2025 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
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| ID | Term |
|---|---|
| D053590 | Interleukin 1 Receptor Antagonist Protein |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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|
| 4 days |
| 4, 7, 14, 28 days |
| Percentage of Participants Surviving (Overall Survival) | Percentage of participants surviving at 14, 28 and 90 days | 14, 28 and 90 days |
| Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) | 28-day Ventilator Free-days | 28 days |
| PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Evolution of PaO2/FiO2 ratio | day 1 to day 14 |
| Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Time to oxygen supply independency | 28 and 90 days |
| Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Time to discharge from hospital | 28 days |
| 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 | 28 and 90 days |
| BG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the site clinicians |
| BG002 | 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 |
| BG003 | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Usual care was provided at the discretion of the site clinicians |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Body Mass Index >= 30 kg/m² | Missing data are possible | Count of Participants | Participants |
|
| Weight | Missing data are possible | Median | Inter-Quartile Range | kg |
|
| SPO2 | Median | Inter-Quartile Range | % |
|
| Temperature | Median | Inter-Quartile Range | °C |
|
| Respiratory rate | Missing data are possible | Median | Inter-Quartile Range | breaths/min |
|
| OG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the site clinicians |
|
|
|
| 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. | Severe COVID population (WHO clinical progression scale =5 at baseline) | Posted | Number | percentage of participants | 4 days |
|
|
|
|
| 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. | Critical COVID population (WHO clinical progression scale >5 at baseline) | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 to Day 14 |
|
|
|
|
| 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 | Critical COVID population (WHO clinical progression scale >5) | Posted | Number | percentage of participants | 4 days |
|
|
|
|
| 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. | 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. | Posted | Median | Inter-Quartile Range | units on a scale | 4, 7, 14, 28 days |
|
|
|
|
| Secondary | Percentage of Participants Surviving (Overall Survival) | Percentage of participants surviving at 14, 28 and 90 days | Posted | Number | 95% Confidence Interval | percentage of participants | 14, 28 and 90 days |
|
|
|
|
| Secondary | Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline) | 28-day Ventilator Free-days | Critical COVID Population (WHO clinical progression scale >5 at baseline) | Posted | Mean | Standard Deviation | days | 28 days |
|
|
|
|
| Secondary | PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | Evolution of PaO2/FiO2 ratio | No statistical comparison was performed due to the limited number of patients with available follow-up data. | Posted | Median | Inter-Quartile Range | mmHg | day 1 to day 14 |
|
|
|
| Secondary | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Time to oxygen supply independency | Posted | Number | 95% Confidence Interval | percentage of participants | 28 and 90 days |
|
|
|
|
| Secondary | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Time to discharge from hospital | Posted | Number | 95% Confidence Interval | percentage of participants | 28 days |
|
|
|
|
| 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 | Patients in the intensive care unit at inclusion | Posted | Number | 95% Confidence Interval | percentage of participants | 28 and 90 days |
|
|
|
|
| 16 |
| 59 |
| 27 |
| 59 |
| 0 |
| 0 |
| EG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the site clinicians | 16 | 55 | 21 | 55 | 0 | 0 |
| EG002 | 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 | 6 | 22 | 14 | 22 | 0 | 0 |
| EG003 | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Usual care was provided at the discretion of the site clinicians | 4 | 20 | 9 | 20 | 0 | 0 |
| Bacterial sepsis | Infections and infestations | Systematic Assessment |
|
| Hepatic cytolysis | Hepatobiliary disorders | Systematic Assessment |
|
| Multiple organ failure | General disorders | Systematic Assessment |
|
| Pulmonary embolism | Vascular disorders | Systematic Assessment |
|
| Acute renal failure | Renal and urinary disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Coronary syndrome | Cardiac disorders | Systematic Assessment |
|
| Cholestatis | Hepatobiliary disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Fungal sepsis | Infections and infestations | Systematic Assessment |
|
| Gastrointestinal bleeding | Gastrointestinal disorders | Systematic Assessment |
|
| Myelomia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Sudden death | Cardiac disorders | Systematic Assessment |
|
| Arterial ischaemia | Cardiac disorders | Systematic Assessment |
|
| Thombopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Complication of intubation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Metastatic progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Herpetic pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Olgivie syndrome | Gastrointestinal disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | Systematic Assessment |
|
| Undertermined sepsis | Infections and infestations | Systematic Assessment |
|
| Diabete | Endocrine disorders | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Meningo-radiculitus | Nervous system disorders | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | Systematic Assessment |
|
| Heart failure | Cardiac disorders | Systematic Assessment |
|
Not provided
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| D007239 |
| Infections |
| D011506 | Proteins |
| D001685 | Biological Factors |
| Male |
|
|
| Day 7 |
|
|
| Day 14 |
|
|
| Day 28 |
|
|
Day 14
| Bayesian Proportionnal odds model |
Adjusted for age and centre |
| Median posterior OR |
| 0.69 |
| 2-Sided |
| 95 |
| 0.33 |
| 1.43 |
% Confidence interval is % Credible interval here |
| Superiority |
| Day 28 | Bayesian Proportionnal odds model | Adjusted for age and centre | Median posterior OR | 0.70 | 2-Sided | 95 | 0.35 | 1.38 | % Confidence interval is % Credible interval here | Superiority |
| Day 4 | Bayesian Proportionnal odds model | Adjusted for age and centre | Median posterior OR | 0.72 | 2-Sided | 95 | 0.22 | 2.39 | % Confidence Interval is % Credible interval here | Superiority |
| Day 7 | Bayesian Proportionnal odds model | Adjusted for age and centre | Median posterior HR | 0.89 | 2-Sided | 95 | 0.28 | 2.80 | % Confidence Interval is % Credible interval here | Superiority |
| Bayesian Proportionnal odds model | Adjusted for afe and centre | Day 14 | Median posterior HR | 0.57 | 2-Sided | 95 | 0.18 | 1.75 | % Confidence Interval is % Credible interval here | Superiority |
| Day 28 |
|
| Day 90 |
|
Adjusted for age and centre |
| Hazard Ratio (HR) |
| 0.77 |
| 2-Sided |
| 95 |
| 0.33 |
| 1.77 |
| Superiority |
| Regression, Cox | adjusted on age and centre | Hazard Ratio (HR) | 0.97 | 2-Sided | 95 | 0.46 | 2.04 | % Confidence interval is % Credible interval here | Superiority | 90 days |
| Regression, Cox | adjusted on age and centre | Hazard Ratio (HR) | 0.64 | 2-Sided | 95 | 0.11 | 3.86 | Superiority |
| Regression, Cox | adjusted on age and centre | Hazard Ratio (HR) | 0.94 | 2-Sided | 95 | 0.19 | 4.68 | Superiority |
| Regression, Cox | adjusted on age and centre | Cox Proportional Hazard | 1.22 | 2-Sided | 95 | 0.31 | 4.87 | Superiority |
| Day 4 |
|
|
| Day 7 |
|
|
| Day 14 |
|
|
| Day 90 |
|
Adjusted for age and centre
Adjusted for age and centre |
| Hazard Ratio (HR) |
| 1.33 |
| 2-Sided |
| 95 |
| 0.58 |
| 3.07 |
| Superiority |
| Day 90 |
|
adjusted on age and centre |
| Hazard Ratio (HR) |
| 0.90 |
| 2-Sided |
| 95 |
| 0.35 |
| 2.34 |
| Superiority |
adjusted on age and centre |
| Hazard Ratio (HR) |
| 1.09 |
| 2-Sided |
| 95 |
| 0.52 |
| 2.29 |
| Superiority |