Clinical trial NCT04331808: CORIMUNO-19 - Tocilizumab Trial - TOCI (CORIMUNO-TOCI)
Official title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Tocilizumab Trial - CORIMUNO-19 - TOCI (CORIMUNO-TOCI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Corona Virus Infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-02
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort
2. Patients belonging to one of the 2 following groups:

   * Group 1: Cases meeting all of the following criteria

     * Requiring more than 3L/min of oxygen
     * OMS/WHO progression scale = 5
     * No Non Invasive Ventilation or High flow
   * Group 2: Cases meeting all of the following criteria

     * Respiratory failure AND (requiring mechanical ventilation OR Non Invasive Ventilation OR High flow)
     * WHO progression scale \>=6
     * No do-not-resuscitate order (DNR order)

Exclusion Criteria:

* Patients with exclusion criteria to the CORIMUNO-19 cohort.
* Known hypersensitivity to Tocilizumab or to any of their excipients.
* Pregnancy
* Current documented bacterial infection
* Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
* Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
* Haemoglobin level: no limitation
* Platelets (PLT) \< 50 G /L
* SGOT or SGPT \> 5N

Primary outcomes:
measure: Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
timeFrame: 4 days
measure: Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline)
timeFrame: Day 1 to Day 14
measure: Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline)
timeFrame: 4 days
measure: Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: Day 1 to Day 14
Secondary outcomes:
measure: Percentage of Participants Surviving (Overall Survival)
timeFrame: 14, 28 and 90 days
measure: WHO Progression Scale
timeFrame: 4, 7 and 14 days
measure: Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)
timeFrame: 28 days
measure: Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency
timeFrame: Day 28, 90
measure: Cumulative Incidence (Percentage of Participants) of Discharge From Hospital
timeFrame: 28, 90 days
measure: Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: 28, 90 days
measure: PaO2/FIO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
timeFrame: day 1 to day 14
Other outcomes:
Locations:
city: Paris
country: France
facility: APHP- Hopital Tenon
city: Paris
country: France
facility: APHP - Beaujon
city: Paris
country: France
facility: APHP - Bichat
city: Paris
country: France
facility: APHP - Hopital Necker
city: Paris
country: France
facility: APHP - Pitié Salpêtrière
city: Paris
country: France
facility: APHP - Saint Louis
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris
name: Xavier MARIETTE, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.