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, with stratification according to site, was performed with the use of a central concealed, Web-based, automated randomization system"
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "double-blind" (report) "blinded (participants, healthcare professionals, investigators, outcome assessors)" (protocol) "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" (registry)
Comment: Blinded study (participants and personnel/carers). Data for the outcomes 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 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: 289 participants randomized; 289 participants analyzed for efficacy; 284 participants analyzed for safety.
Data available for all or nearly 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 protocol with statistical analysis plan (23 June 2020) and prospective trial registry (13 July 2020) were available.
Outcomes were 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 |