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 |
Published Manuscript: "Trial procedures
were minimal but rigorous, with data entry through
a cloud-based Good Clinical Practice–compliant
clinical data management system that recorded
demographic characteristics, respiratory support,
coexisting illnesses, and local availability of trial
drugs before generating the treatment assignment."
Preprint: "Online randomization of consented patients (via a cloud-based GCP-compliant clinical data management system)" Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Comment: Unblinded study (participants and personnel/carers).
Deviations from intended intervention arising because of the study context: Crossover: "for other drugs adherence midway was 94% to 95%, and crossover was 2 to 6%." (deviation too small to affect the outcome). Administration of co-interventions of interest, antivirals, corticosteroids and biologics were reported and balanced. Hence, deviations did not arise because of the trial context. Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcome: Mortality (D28). |
| Missing outcome data |
Low |
Comment: 2791 patients randomized, 2771 patients analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcome: Mortality (D28). |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) Mortality is an observer-reported outcome, not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). |
| Selection of the reported results |
Low |
Comment: The prospective registry and protocol are available.
Mortality is specified in the protocol as reported in the paper. No timepoint of measurement is provided in the protocol but for this outcome, we do not suspect selective reporting of the results. Results were probably not selected from multiple outcome measurements not analyses of the data. Trial probably analyzed as pre-specified. Risk assessed to be low for the outcome: Mortality (D28). |
| Overall risk of bias |
Low |