Trial NCT04324073
Publication - Hermine O, Eur Respir J, 2022 (published paper)
Dates: 2020-03-27 to 2020-04-07
Funding: Public/non profit (Assistance Publique - Hôpitaux de Paris)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / France Follow-up duration (days): 90 | |
| Inclusion criteria | Confirmed SARS CoV-2 infection (positive on RT-PCR and/or typical chest CT scan) with critical pneumonia (O2>3L/min, WHO Clinical Progression Scale [WHO-CPS] score > 5; Patients with non-invasive ventilation (NIV) or mechanical ventilation (MV) |
| Exclusion criteria | Known hypersensitivity to Sarilumab 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 |
| Interventions | |
| Treatment
Sarilumab 400 mg IV infusion once-off; second infusion at day 3 in absence of clinical response |
|
| Control
Standard care ( / ) Definition of Standard care: * | |
| Participants | |
| Randomized 91 participants (n1=50 / n2= 41) | |
| Characteristics of participants N=91 Mean age : NR 62 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=25 Critical: n=56 | |
| Primary outcome | |
| In the register 1. Survival without needs of ventilator utilization at day 14. [ Time Frame: 14 days ] Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR. 2. WHO progression scale <=5 at day 4 [ Time Frame: 4 days ] Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR 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 | |
| In the report 1)The early co-primary outcome is the proportion of patients with a decrease of WHO score of at least 1 point at day 4. 2) The longer-term co-primary outcome is the 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 NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. | |
| Documents available |
Protocol NR Statistical plan NR Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment |
In addition to the published article, the study registry was used in data extraction and risk of bias assessment.
Data was extracted from The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499–518.
The study was updated on March 16th, 2022 with data from the published report. |