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: “All participants were centrally randomized to study intervention using an interactive web response system”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “In this double-blind study, neither participants, investigators, nor the sponsor study team were aware of treatment assignments prior to the final data base lock at the conclusion of the study arm.”
Comment: Blinded study (participants and personnel/carers) 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). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 1049 participants randomized; 1035 participants analyzed for safety; 973 participants completed follow up for efficacy; 973 participants analyzed for viral conversion.
ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. Data available for all or nearly all participants randomized for safety. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. HOSPITALIZATION OR DEATH. MORTALITY. INCIDENCE OF VIRAL NEGATIVE CONVERSION. Data not available for all or nearly all participants randomized for efficacy. No evidence that the result is not biased. Reasons: 5.0% vs. 6.9% Did not complete the 29-day treatment period, did not yet transition to follow-up period, or the trial site did not update the disposition status at time of data lock; 0.4% vs. 0.2% lost to follow up. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). |
| 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: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry 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 some concerns for the outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |