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: "Participants were randomized (1:1) using a computer-generated random-number list".
"Random allocation was done remotely by a member of the study team not involved in participants' enrollment." Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "open label"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation arose because of the trial context. Our analysis for the binary outcome 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: Hospitalization or Death. Mortality (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 353 participants randomized; 353 participants analyzed for adverse and serious adverse events, 293 participants analyzed for hospitalization or death, mortality and WHO score 7 and above.
ADVERSE and SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for outcomes: Adverse events. Serious adverse events. HOSPITALIZATION OR DEATH, MORTALITY, WHO SCORE 7 AND ABOVE Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data: negative RT-PCR at baseline (not missing data hence not accounted for in this domain), missing RT-PCR at all follow-up visits, or consent withdrawal. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (same reasons and equal proportion of missingness between arms). Risk assessed to be some concerns for the outcomes: Hospitalization or Death. Mortality (D28). WHO score 7 and above (D28). |
| Measurement of the outcome |
Some concerns |
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. For WHO score 7 and above and hospitalization or death, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for outcomes: Hospitalization or death. Mortality (D28). WHO score 7 and above (D28). Adverse events and serious adverse events may contain both clinically- and laboratory-detected outcomes, therefore it can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The registry was available and utilized.
MORTALITY Mortality was not pre-specified in the registry but we consider this acceptable for this outcome as mortality should be reported even if not planned. Result was probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for outcome: Mortality (D28). WHO SCORE 7 AND ABOVE, HOSPITALIZATION OR DEATH, AE, SAE Outcome not pre-specified in the registry. No information on whether the results were selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Hospitalization or death. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |