Coronaviridae Infections, Coronavirus Infection, Nidovirales Infections, Respiratory Tract Disease, Respiratory Tract Infections, RNA Virus Infections, SARS (Severe Acute Respiratory Syndrome), Virus Diseases
Conditions
Brief summary
The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab combined with Dexamethasone 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 Dexamethasone alone or Dexamethasone +Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care (including Dexamethasone) treated patients
Interventions
DRUGTocilizumab
Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3
DRUGDexamethasone
Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
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 belonging to the following group: * Requiring ≥ 3L/min of oxygen * WHO progression scale = 5 * No NIV or High flow
Exclusion criteria
* Patients with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival without needs of invasive ventilation at day 14 | day 14 | Survival without needs of invasive ventilation at day 14. Thus, events considered are mechanical (invasive) ventilation or death. A new DNR order will be considered as an event at the actual date of care limitation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival without needs of ventilator utilization at day 14 | 14 days | Survival without needs of ventilator utilization (including non-invasive ventilation and Optiflow) at day 14 |
| WHO progression scale at day 7 and 14 | day 7 and day 14 | 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 |
| Cumulative incidence of oxygen supply independency at 14 and 28 days | 14 and 28 days | Cumulative incidence of oxygen supply independency |
| Cumulative incidence of discharge alive at 14 and 28 days | 14 and 28 days | Cumulative incidence of discharge alive |
| Survival without needs of mechanical ventilation at day 1 | day 1 | Survival without needs of mechanical ventilation at day 1. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR. |
| Overall survival at 14, 28, 60 and 90 days | 14, 28, 60 and 90 days | Overall survival |
Countries
French Guiana
Outcome results
None listed