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: "Patients were enrolled, randomised, and allocated to the appropriate treatments by the investigators/subinvestigators using an interactive web response system, which was managed by the sponsor."
Comment: Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “Double-blinded. ”
Comment: Blinded study (participants and personnel/carers) for first 14 days of 28-day follow up period. After 14 days unblinded physicians could prescribe non-study drugs. This could not affect negative clearance at day 14, but potentially could affect other outcomes to day 28. Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: antivirals, corticosteroids or biologics. Hence, no information on whether deviations arose because of the trial context. MORTALITY. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS. 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 some concerns for the outcomes: Mortality (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. (TIME TO) VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 4 vs 3 participants were excluded from the efficacy analysis post-randomization because they tested negative for SARS-CoV-2 on Day 1. One participant from each arm was excluded from the safety analysis post-randomization because they did not receive the study drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Time to viral negative conversion. |
| Missing outcome data |
Low |
Comment: 155 participants randomized; 153 participants analyzed for safety; 148 participants analyzed for mortality, viral negative conversion, WHO score 7 and above.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| 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, (TIME TO) VIRAL NEGATIVE CONVERSION Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO SCORE 7 AND ABOVE For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: WHO score 7 and above (D28). ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which 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 the outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan (Nov 20, 2020), and registries (Nov 11, 2020 and Dec 8, 2020) were available.
Outcome pre-specified in the registries and/or protocol. 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 outcome: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |