Trial NCT04401579
Publication Kalil AC, N Engl J Med, 2020
Primary outcome on the report: Time to recovery, with the day of recovery defined as the first day, during the 28 days after enrollment, on which a patient attained category 1, 2, or 3 on the eight-category ordinal scale

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: “Randomization was stratified by study site and disease severity at enrollment and was performed using a web-based Internet Data Entry System, Advantage eClinical”
Comment: Allocation sequence random. Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance
Deviations from intervention
Low 		Quote: “Randomized double-blind placebo-controlled trial”; "The trial team was unaware of the trial-group assignments until after all data queries were resolved and the database was locked."
Comment: Blinded study (participants and personnel/carers).
Our analysis for the outcomes is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 1033 participants randomized; 1033 participants analyzed; 1016 participants analyzed for safety.
Data available for all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Measurement of the outcome
Low 		Comment: Method of measuring the 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. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective protocol (dated April 19th, 2020), statistical analysis plan, retrospective registry (dated May 26th, 2020) were available.
Outcomes pre-specified.
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. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Overall risk of bias
Low