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 will be centralized and will be performed via an Interactive Web Response System after subject inclusion. A randomization list containing the randomization numbers and the corresponding randomized treatment assignments will be generated and stored in a secured area that is only accessible to the randomization team."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Some concerns |
Quote: “Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)”
Comment: Blinded study (participants and personnel/carers) Participants were analyzed according to their randomized groups for the outcome. Of note, 4 patients were excluded from 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: Hospitalization or death. Mortality (D28). Mortality (D60 or more). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Serious adverse events. |
Missing outcome data |
Some concerns |
Comment: 465 participants randomized; 461 participants analyzed for mortality and serious adverse events; 431 participants analyzed for Hospitalization or death and WHO Score 7 and above; 428 participants analyzed for Incidence of viral negative conversion.
MORTALITY. SERIOUS ADVERSE EVENTS. Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Serious adverse events. HOSPITALIZATION OR DEATH. WHO SCORE 7 AND ABOVE. Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 10 vs 9 vs 11 due to missing data at the given time point. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Hospitalization or WHO score 7 and above (D28). INCIDENCE OF VIRAL NEGATIVE CONVERSION. Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 9 vs 12 vs 9 due to missing test results at the given visit. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: 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). Mortality (D60 or more). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry (consulted up to version dated 20 Apr 2021) were available.
Outcome 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 outcome: Mortality (D28). Mortality (D60 or more). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Serious adverse events. |
Overall risk of bias |
Some concerns |