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 |
Comment:"Randomization was performed using a validated interactive voice/web response system and stratified based on two categories of patient clinical status at baseline"
Comment: Allocation sequence random. Allocation sequence concealed. |
Deviations from intervention |
Some concerns |
Quote: “All site staff, patients, and caregivers were blinded to treatment assignment, except an unblinded pharmacist who prepared the study treatments"
Comment: Blinded study (participants and personnel/carers) MORTALITY. CLINICAL IMPROVEMENT. 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 low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D60 or more). Adverse events. Serious adverse events. TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT. Participants were analyzed according to their randomized groups for the time-to-event outcomes. Of note, 1 participant in each arm was excluded from the analysis post-randomization because they did not receive the drug. Outcomes for participants lost to follow up (balanced between groups) were imputed. 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: Time to death. Time to clinical improvement. |
Missing outcome data |
Low |
Comment: 227 participants randomized; 212 participants with complete follow up analyzed with imputation for time-to-event outcomes; 225 participants analyzed for mortality and safety.
Data available for all or nearly all participants randomized for mortality and safety. Data not available for all or nearly all participants randomized for time-to-event outcomes. No evidence that the result is not biased. Reasons: 3 vs. 3 were lost to follow up; 2 vs. 3 participants withdrew; 1 vs. 0 were withdrawn because of an adverse event; 1 vs. 0 were withdrawn because of a protocol violation. Missingness could on the true value of the outcome. Not likely that missingness depended on the true value of the outcome because of blinding and balance between arms. This potential source of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). Time to clinical improvement. 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). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry 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 outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |