Lescure 2021.

Study characteristics
Methods	RCT Blinding: quadruple blinding Date of study: from 28 March 2020 to 3 July 2020 Location: multicentre (45 centres) / Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain Follow‐up duration (days): 60
Participants	Population: patients with confirmed (any specimen) COVID‐19 (moderate‐critical) admitted to 45 centres in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. Randomised: 420 participants (n1 sarilumab 400 mg = 173/ n2 sarilumab 200 mg = 161/ n3 control = 86) Characteristics of participants Mean age: 58 to 60 years 261 males Admitted to ICU: n = 148 Severity: mild: n = 2 / moderate: n = 304/ severe: n = 60 / critical = 50 Patients on oxygen without intubation: n = 364 (87%); Intubated: n = 50 (12%) C‐reactive protein (median): 94.6 (48.1 to 167.9) mg/L 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 randomization 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 ICU) Exclusion criteria Patients with at least 1 of the following: in the investigator’s 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;AST or 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; tumour necrosis factor a inhibitors within 2 to 8 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 (e.g. 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 Dropouts and withdrawals: 0% dropout, withdrawal due to AEs: NR
Interventions	Intervention Sarilumab 400 mg (400 mg IV infusion, a 2nd dose could be administered 24 to 48 hours after the 1st) Sarilumab 200 mg (200 mg IV infusion, a 2nd dose could be administered 24 to 48 hours after the 1st) Control: placebo Definition of standard care: local standard of care Co‐interventions Steroid use at baseline or any time during the study Sarilumab 400 mg: 78 (45%) Sarilumab 200 mg: 58 (36%) Placebo: 39 (45%)
Outcomes	Primary outcome of the trial Time from baseline to clinical improvement of ≥ 2 points on a 7‐point ordinal scale. Discharge prior to day 29 was considered as a 2‐point improvement. Note: the definition of clinical improvement extracted is improvement from baseline by at least 2 categories on a 7‐point ordinal scale
Notes	Funding: private (Sanofi and Regeneron Pharmaceuticals, Inc) Conflict of interest: yes, declared. F‐XL has received lecture fees from Merck Sharp & Dohme and Gilead Science. HH has nothing to disclose of relevance to this study. RF has no financial conflicts to disclose. JSL, GS, PW, NP, and OH are employees of Sanofi and may hold stock and/or stock options in the company. Protocol: NR Statistical plan: NR Data‐sharing stated: yes, currently available Data accessibility: clinicalstudydatarequest.com/ Overall comment: in addition to the pre‐print article, the supplementary materials, and the study registry were used in data extraction and r'Rsk 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).