Rosas COVACTA 2021.

Study characteristics
Methods	RCT Blinding: double‐blinding Date of study: from 3 April 2020 to 28 July 2020 Location: multicentre: Canada, Denmark, France, Germany, Italy, the Netherlands, Spain, UK, USA Follow‐up duration (days): 60
Participants	Population: patients with confirmed COVID‐19 (mild to critical) Randomised: 452 participants (n1 tocilizumab arm = 301 / n2 control arm = 151) Characteristics of participants N = 452 Mean age: 60.8 years 306 Males Admitted to ICU: n = 247 (56%) Severity: mild: n = 15 / moderate: n = 122/ severe: n = 133/ critical: n = 168 Patients on oxygen without intubation n = 255 (56%); Intubated n = 168 (37%) C‐reactive protein (median): 150.3 to 157.2 mg/L Inclusion criteria Patients 18 years or older with severe COVID‐19 pneumonia confirmed by positive polymerase chain reaction test in any body fluid and evidenced by bilateral chest infiltrates on chest x‐ray or CT were enrolled. Eligible patients had blood oxygen saturation ≤ 93% or partial pressure of oxygen/fraction of inspired oxygen < 300 mm/Hg. Informed consent was obtained for all enrolled patients. Exclusion criteria Patients were excluded if the treating physician determined that death was imminent and inevitable within 24 hours or if they had active tuberculosis or bacterial, fungal, or viral infection other than SARS‐CoV‐2. Dropouts and withdrawals :14/452 (3%); 0 withdrawal due to AEs
Interventions	Intervention: tocilizumab (8 mg/kg infusion, maximum 800 mg), a second infusion could be administered 8 to 24 hours after the first) Control: placebo Co‐interventions Steroid use at baseline or any time during the study Tocilizumab: 57 (19%) Placebo: 41 (28%)
Outcomes	Primary outcome of the trial Clinical status assessed on a 7‐category ordinal scale at day 28 Note: the definition of clinical improvement extracted is improvement from baseline by at least 2 categories on the ordinal scale
Notes	Funding: mixed (F. Hoffmann‐La Roche Ltd; Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority) Conflict of interest: yes. (Quote:) “I.O.R. received a grant from Roche/Genentech during the conduct of the study; a grant and personal fees from Genentech outside the submitted work; and personal fees from Boehringer and Bristol‐Myers Squibb outside the submitted work. A.M.’s institution received grant support from Roche/Genentech during the conduct of the study; he has received funding from the National Institutes of Health outside the submitted work and medical education from Merck and Livanova outside the submitted work.” Protocol: yes, available Statistical plan: yes, available Data‐sharing stated: yes, through vivli.org Overall comment: in addition to all available versions of the pre‐print article, the study registry and supplementary appendix, as well as responses from contact with authors were used in data extraction and 'Risk of bias' assessment. The protocol and statistical analysis plan were not available although it was sent by authors after requested. The full data could not be accessed. Patients in the tocilizumab group received a 2nd dose only if their condition did not improve or worsened. The study achieved the target sample size prespecified in the registry. There is no change from the trial registration in the intervention and control treatments as well as primary outcome. Some secondary outcomes in the registry were not reported in the pre‐print article, particularly regarding the 60‐day time point as well. The sponsor (Hoffman‐La Roche Ltd.) played a prominent role, with writing support for the authors provided by Sara Duggan, Ph.D., of ApotheCom, funded by F. Hoffmann‐La Roche Ltd. 3 authors were employees of Roche Products Ltd. On 7 December 2020, we received additional information from authors on this study. This study was updated with data from contact with authors on 13 January 2021. This trial was updated on 1 March 2021 after publication of the study report.