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The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort. Tocilizumab 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 Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-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 |
|---|---|---|---|
| TOCILIZUMAB -- Severe COVID Population (WHO Clinical Progression Scale =5 at baseline) | Experimental | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) CPS: Clinical Progression Scale |
|
| Standard of care -- Severe COVID Population (WHO Clinical Progression Scale =5 at baseline) | No Intervention | Usual care was provided at the discretion of the clinicians | |
| TOCILIZUMAB -- Critical COVID Population (WHO Clinical Progression Scale >5 at baseline) | Experimental | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) CPS: Clinical Progression Scale |
|
| Standard of care -- Critical COVID Population (WHO Clinical Progression Scale >5 at baseline) | No Intervention | Usual care was provided at the discretion of the clinicians |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tocilizumab | Drug | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 4 days |
| 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. | Day 1 to Day 14 |
| 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 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Surviving (Overall Survival) | Percentage of participants surviving at 14, 28 and 90 days | 14, 28 and 90 days |
| 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 |
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Inclusion Criteria:
Patients included in the CORIMUNO-19 cohort
Patients belonging to one of the 2 following groups:
Group 1: Cases meeting all of the following criteria
Group 2: Cases meeting all of the following criteria
Exclusion Criteria:
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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 |
|---|---|---|---|---|---|---|
| APHP- Hopital Tenon | Paris | 75012 | France | |||
| APHP - Beaujon |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33080017 | Result | Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):32-40. doi: 10.1001/jamainternmed.2020.6820. | |
| 34028504 | Result |
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| ID | Title | Description |
|---|---|---|
| FG000 | TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
| FG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the clinicians |
| FG002 | TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
| FG003 | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Usual care was provided at the discretion of the clinicians |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
| BG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) |
| 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 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 | Severe COVID Population (WHO clinical progression scale =5 at baseline) | Posted | Number | percentage of participants | 4 days |
|
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 | TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac 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 | Yes | No | No | Study Protocol | May 4, 2020 | Jul 25, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 13, 2020 | Jul 25, 2024 | 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 |
|---|---|
| C502936 | tocilizumab |
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| 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 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 |
| 4, 7 and 14 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 |
| Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Time to oxygen supply independency | Day 28, 90 |
| Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Time to discharge from hospital | 28, 90 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, 90 days |
| PaO2/FIO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | 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. | day 1 to day 14 |
| Paris |
| France |
| APHP - Bichat | Paris | France |
| APHP - Hopital Necker | Paris | France |
| APHP - Pitié Salpêtrière | Paris | France |
| APHP - Saint Louis | Paris | France |
| CHU Strasbourg | Strasbourg | France |
| Institut Gustave Roussy | Villejuif | France |
| Mariette X, Hermine O, Tharaux PL, Resche-Rigon M, Steg PG, Porcher R, Ravaud P. Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19: A Follow-up of the CORIMUNO-TOCI-1 Randomized Clinical Trial. JAMA Intern Med. 2021 Sep 1;181(9):1241-1243. doi: 10.1001/jamainternmed.2021.2209. |
| 35115337 | Result | Hermine O, Mariette X, Porcher R, Resche-Rigon M, Tharaux PL, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. Eur Respir J. 2022 Aug 10;60(2):2102523. doi: 10.1183/13993003.02523-2021. Print 2022 Aug. |
| 41574613 | Derived | Lenoir O, Morin F, Walter-Petrich A, Resmini L, Zaidan M, Mahtal N, Ferlicot S, Puelles VG, Wanner N, Dang J, d'Izarny-Gargas T, Biermann J, Izar B, Baron S, Terrier B, Massy ZA, Essig M, Couturier A, May O, Belenfant X, Buob D, Brocheriou I, Izzedine H, Lombardi Y, Francois H, Moktefi A, Audard V, Sannier A, Daugas E, Jamme M, Henry G, Le Monnier de Gouville I, Marie C, Homyrda L, Verstuyft C, Tubiana S, Kafif O, Piquard V, Dougados M, Huber TB, Livrozet M, Hulot JS, Laouenan C, Ghosn J, Mentre F, Karras A, Yazdanpanah Y, Porcher R, Ravaud P, Caillat-Zucman S, Mariette X, Hermine O, Resche-Rigon M, Tharaux PL; CORIMUNO-19 collaborative group. Levels of circulating kidney injury markers and IL-10 identify non-critically ill patients with COVID-19 at risk of death. JCI Insight. 2026 Jan 23;11(2):e198244. doi: 10.1172/jci.insight.198244. eCollection 2026 Jan 23. |
| 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. |
| 33201228 | Derived | Tleyjeh IM. The Misleading "Pooled Effect Estimate" of Crude Data from Observational Studies at Critical Risk of Bias: The Case of Tocilizumab in Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2021 Jun 15;72(12):e1154-e1155. doi: 10.1093/cid/ciaa1735. No abstract available. |
Usual care was provided at the discretion of the clinicians |
| BG002 | TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
| BG003 | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Usual care was provided at the discretion of the 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 | kg/m² | Missing data are possible | Median | Inter-Quartile Range | kg/m² |
|
| Weight | Missing data are possible | Median | Inter-Quartile Range | kg |
|
| SPO2 | Missing data are possible | Median | Inter-Quartile Range | % |
|
| Temperature | Median | Inter-Quartile Range | °c |
|
| OG000 | TOCILIZUMAB -- Severe COVID Population (WHO-CPS =5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) |
| OG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the clinicians |
|
|
|
| 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. | Severe 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 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 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 | Critical 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 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 |
|
|
|
|
| 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 | 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 | Missing data are possible | Posted | Median | Inter-Quartile Range | units on a scale | 4, 7 and 14 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 | Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency | Time to oxygen supply independency | No assessment in Severe COVID Population (WHO Clinical Progression Scale =5 at baseline) at Day 90 | Posted | Number | 95% Confidence Interval | percentage of participants | Day 28, 90 |
|
|
|
|
| Secondary | Cumulative Incidence (Percentage of Participants) of Discharge From Hospital | Time to discharge from hospital | No assessment in Severe COVID Population (WHO Clinical Progression Scale =5 at baseline) at Day 90 | Posted | Number | 95% Confidence Interval | percentage of participants | 28, 90 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 | Critical COVID Population (WHO clinical progression scale >5 at baseline) Patients in intensive care unit at inclusion | Posted | Number | 95% Confidence Interval | percentage of participants | 28, 90 days |
|
|
|
|
| Secondary | PaO2/FIO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline) | 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. | 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 |
|
|
|
| 7 |
| 63 |
| 20 |
| 63 |
| 0 |
| 0 |
| EG001 | Standard of Care -- Severe COVID Population (WHO-CPS =5) | Usual care was provided at the discretion of the clinicians | 11 | 67 | 29 | 67 | 0 | 0 |
| EG002 | TOCILIZUMAB -- Critical COVID Population (WHO-CPS >5) | Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) | 12 | 49 | 31 | 49 | 0 | 0 |
| EG003 | Standard of Care -- Critical COVID Population (WHO-CPS >5) | Usual care was provided at the discretion of the clinicians | 13 | 43 | 27 | 43 | 0 | 0 |
| Anemia | General disorders | Systematic Assessment |
|
| Hyperlipasemia | Gastrointestinal disorders | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | Systematic Assessment |
|
| Hepatic cytolysis | Hepatobiliary disorders | Systematic Assessment |
|
| Multiple organ failure | General disorders | Systematic Assessment |
|
| Pulmonary embolism | Vascular disorders | Systematic Assessment |
|
| Fever | Infections and infestations | Systematic Assessment |
|
| Hyperkaliemia | Renal and urinary disorders | Systematic Assessment |
|
| Hyperglycaemia | Endocrine disorders | Systematic Assessment |
|
| Hypertension | Cardiac disorders | Systematic Assessment |
|
| Acute renal failure | Renal and urinary disorders | Systematic Assessment |
|
| Arterial ischemia | Cardiac disorders | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Bacterial sepsis | Infections and infestations | Systematic Assessment |
|
| Fungal sepsis | Infections and infestations | Systematic Assessment |
|
| Viral sepsis | Infections and infestations | Systematic Assessment |
|
| Tetraparesis | Nervous system disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Angina | Cardiac disorders | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hemorrhagic stroke | Nervous system disorders | Systematic Assessment |
|
| Ischemic stroke | Nervous system disorders | Systematic Assessment |
|
| Hypovolemic shock | Cardiac disorders | Systematic Assessment |
|
| Diabetes | Endocrine disorders | Systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | Systematic Assessment |
|
| Thrombopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Severe acute pancreatis | Gastrointestinal disorders | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | Systematic Assessment |
|
| Hyperleukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
|
| Arterial hypertension | Cardiac disorders | Systematic Assessment |
|
| Metabolic acidosis | Renal and urinary disorders | Systematic Assessment |
|
| Guillain Barré syndrome | Nervous system disorders | Systematic Assessment |
|
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Gastrointestinal bleeding | Gastrointestinal disorders | Systematic Assessment |
|
| Bleeding | Blood and lymphatic system disorders | Systematic Assessment |
|
| Limb ischemia | Cardiac disorders | Systematic Assessment |
|
| Neuropathy | Nervous system disorders | Systematic Assessment |
|
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Tracheotomy | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Psoas hematoma | Vascular disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Heart failure | Cardiac disorders | Systematic Assessment |
|
| Facial paralysis | Nervous system disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D007239 |
| Infections |
| Male |
|
| Day 28 |
|
| Day 90 |
|
adjusted for age and centre |
| Cox Proportional Hazard |
| 0.92 |
| 2-Sided |
| 95 |
| 0.33 |
| 2.53 |
| Superiority |
| Day 90 | Regression, Cox | adjusted for age and centre | Cox Proportional Hazard | 0.64 | 2-Sided | 95 | 0.25 | 1.65 | Superiority |
| Day 14 | Regression, Cox | adjusted for age and centre | Hazard Ratio (HR) | 0.37 | 2-Sided | 95 | 0.12 | 1.15 | Superiority |
| Day 28 | Regression, Cox | adjusted for age and centre | Hazard Ratio (HR) | 0.69 | 2-Sided | 95 | 0.32 | 1.47 | Superiority |
| Day 90 | Regression, Cox | adjusted for age and centre | Hazard Ratio (HR) | 0.67 | 2-Sided | 95 | 0.30 | 1.49 | Superiority |
|
| Day 7 |
|
|
| Day 14 |
|
|
Day 7 |
| Proportionnal odds model |
Bayesian analysis. Adjusted for age and centre |
| Median posterior OR |
| 0.86 |
| 2-Sided |
| 95 |
| 0.43 |
| 1.71 |
| Superiority |
% Confidence Interval is % Credible Interval here |
| Day 14 | Proportionnal odds model | Bayesian analysis. Adjusted for age and sex | Median posterior OR | 0.76 | 2-Sided | 95 | 0.40 | 1.42 | % Confidence Interval is % Credible Interval here | Superiority |
| Day 4 | Proportionnal odds model | Bayesian analysis. Adjusted for age and centre | Median posterior OR | 0.85 | 2-Sided | 95 | 0.39 | 1.82 | Superiority | % Confidence Interval is % Credible Interval here |
| Day 7 | Proportionnal odds model | Bayesian analysis. Adjusted for age and centre | Median posterior OR | 0.69 | 2-Sided | 95 | 0.32 | 1.47 | % Confidence Interval is % Credible Interval here | Superiority |
| Day 14 | Proportionnal odds model | Bayesian analysis. Adjusted for age and centre | Median posterior OR | 0.68 | 2-Sided | 95 | 0.32 | 1.43 | % Confidence Interval is % Credible Interval here | Superiority |
|
| Day 90 |
|
|
| Hazard Ratio (HR) |
| 1.44 |
| 2-Sided |
| 95 |
| 0.82 |
| 2.52 |
| Superiority |
| Day 90 | Fine-Gray model | adjusted on age and centre | Hazard Ratio (HR) | 1.28 | 2-Sided | 95 | 0.80 | 2.03 | Superiority |
|
| Day 90 |
|
|
adjusted for age and centre |
| Hazard Ratio (HR) |
| 1.45 |
| 2-Sided |
| 95 |
| 0.80 |
| 2.63 |
| Superiority |
| Day 90 | Fine-Gray model | adjusted for age and centre | Hazard Ratio (HR) | 1.35 | 2-Sided | 95 | 0.84 | 2.17 | Superiority |
adjusted on age and centre |
| Hazard Ratio (HR) |
| 1.28 |
| 2-Sided |
| 95 |
| 0.73 |
| 2.24 |
| Superiority |
| Day 4 |
|
|
| Day7 |
|
|
| Day 14 |
|
|