Trial NCT04327388, EudraCT 2020-001162-12
Publication Lescure FX, medRxiv, 2021 (quadruple blinding)
Dates: 3/28/2020 to 7/3/2020
Funding: Private (Sanofi and Regeneron Pharmaceuticals, Inc)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: preprint | |
| Location :
Multicenter / Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain Follow-up duration (days): 60 | |
| Inclusion criteria | Patients aged 18 years or older at the time of signing informed consent ; Hospitalised for laboratory-confirmed SARS-CoV-2 infection in any specimen within 2 weeks prior to randomisation ; Evidence of pneumonia by chest imaging or chest auscultation and no alternative explanation for current clinical presentation ; Meet criteria for severe disease (defined as administration of supplemental oxygen by nasal cannula, simple face mask, or another similar device) or critical disease (defined as need for supplemental oxygen delivered by nonrebreather mask or high-flow nasal cannula, use of invasive or noninvasive ventilation, or treatment in an intensive care unit) |
| Exclusion criteria | Patients with at least one of the following: in the investigatorâs opinion, a low probability of surviving 48 hours or remaining at the investigational site beyond 48 hours ; Dysfunction of >=2 organ systems or need for extracorporeal life support or renal replacement therapy at screening ; Absolute neutrophil count <2000/mm3; aspartate aminotransferase or alanine aminotransferase (ALT) exceeding 5-fold upper limit of normal (ULN) at screening ; Platelets <50,000/mm3 at screening ; Known active, incompletely treated, suspected or known extrapulmonary tuberculosis ; Prior or concurrent use of immunosuppressants at screening, including, but not limited to, IL-6 inhibitors or Janus kinase inhibitors within 30 days of baseline ; Anti-CD20 agents without evidence of B-cell recovery to baseline levels or IL-1 receptor antagonist (anakinra) within 1 week of baseline ; Abatacept within 8 weeks of baseline; tumor necrosis factor a inhibitors within 2â8 weeks of baseline ; Alkylating agents, including cyclophosphamide, within 6 months of baseline ; Cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, or methotrexate within 4 weeks of baseline ; Intravenous (IV) immunoglobulin within 5 months of baseline ; Use of systemic chronic (eg, oral) corticosteroids for a condition not related to COVID-19 at doses higher than prednisone 10 mg/day or equivalent at screening ; Suspected or known active systemic bacterial or fungal infections within 4 weeks of screening |
| Interventions | |
| Treatment 1 Sarilumab 400mg (400 mg) Co-Intervention: Standard care | |
| Control Placebo | |
| Treatment 3 Sarilumab 200mg (200 mg) Co-Intervention: Standard care | |
| Participants | |
| Randomized 420 participants n1=173/ n2=86/ n3=161 | |
| Characteristics of participants N=420 Mean age : NR 261 males Severity : Mild: n=2 / Moderate: n=304/ Severe: n=60 Critical: n=50 | |
| Primary outcome | |
| In the register Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale [ Time Frame: Baseline to Day 29 ]The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse. | |
| In the report Time from baseline to clinical improvement of â¥2 points on a 7-point ordinal scale. Discharge prior to day 29 was considered as a 2-point improvement. | |
| Documents avalaible |
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 pre-print article, the supplementary materials, and the study registry were used in data extraction and risk of bias assessment. Neither study protocol nor statistical analysis plan were available. There were no substantive differences between the prospective registry and the pre-print article. The study was an adaptive design and any changes in protocol versions are reported with rationales in the article. The study achieved its pre-stated sample size. As this study was conducted in 11 countries across 45 sites, standard of care may have differed (supported by concomitant medication use presented in Table S2). |