Trial NCT04338009
Publication Cohen J, Lancet Respir Med, 2021
Primary outcome on the report: Global rank score in which each participant was ranked against all other participants across four hierarchies of clinical outcomes collected over the duration of the hospitalisation: (1) days to death during the hospitalisation (ranked lowest to highest); followed by (2) days on invasive mechanical ventilation or extracorporeal membrane oxygenation (ranked highest to lowest); followed by (3) days on renal replacement therapy or inotropic or vasopressor therapy (ranked highest to lowest); followed by (4) area under the curve (AUC) of a modified SOFA score

Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.

Bias Author's judgement Support for judgement
Randomization
Low 		Quote: "Randomisation lists were generated by a statistician at the data coordinating centre (University of Pennsylvania, Philadelphia, PA, USA) using a standard random number generator in Stata version 16.1 with permuted block randomisation in randomly varying block sizes of two, four, or six by clinical site, sex, and age. Randomisation was controlled centrally by the data coordinating centre. Allocation was concealed using a secure web-based randomisation system."
Comment: Allocation sequence random. Allocation sequence concealed.
Deviations from intervention
Some concerns 		Quote: “randomized open-label blinded end point trial”
Comment: Unblinded study.
Administration of co-interventions of interest - antivirals, biologics, and corticosteroids - was reported and balanced between groups.
24 participants crossed over between treatment assignments (17 assigned to the continuation group and 7 assigned to the discontinuation group).
Result of "sensitivity analyses in which participants were censored at the time of crossover,[and] no significant differences in study endpoints were observed between treatment groups", the deviations were not considered to affect the outcome.
Data were analyzed using intention-to-treat analysis, which, to estimate the effect of assignment to intervention, is considered appropriate.
Risk assessed to be some concerns for outcomes: Mortality (D28). Time to death.
Missing outcome data
Low 		Comment: 152 patients randomized; 152 patients analyzed.
Data available for all patients.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death.
Measurement of the outcome
Low 		Quote: “Investigators and treating clinicians were aware of the assigned treatment strategy, but outcome adjudicators were not. A clinician panel was appointed to do masked adjudications of the outcome events. Each site used a standardised approach to redacting patient records so that the adjudicators were fully masked to the treatment assignments but were able to assess other important components of the hospitalisations.”
Comment: Method of measuring outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality (D28). Time to death.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan, and registry were available.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death.
Overall risk of bias
Some concerns