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: “The randomization schedule is generated using Sealed Envelope, a web-based randomization service, by the unblinded study Biostatistician. The randomization schedule is provided to the research pharmacist designated for the study in each trial center. The research pharmacist prepares the study drug for infusion on the day of dosing based on the randomization schedule and labels the infusion bag with the subject number but no treatment assignment information. The investigators, study coordinators, study subjects are blinded to the treatment assignment and do not have access to the randomization schedule.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “randomized, double-blind, placebo-controlled trial. The investigators, study coordinators, study subjects are blinded to the treatment assignment.”
Comment: Blinded study (participants and personnel/carers). MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE 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 outcome: Mortality (D28). Clinical improvement (D28). WHO score 7 and above. Adverse events. Serious adverse events. TIME TO DEATH, TIME TO CLINICAL IMPROVEMENT, TIME TO WHO SCORE 7 AND ABOVE Participants were analyzed according to their randomized groups for the time-to-event outcome. Of note, 0 vs 1 participants were excluded from the analysis post-randomization for reasons other than missing data. Nevertheless, we consider the analysis appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for outcome: Time to death. Time to clinical improvement. Time to WHO score 7 and above. |
| Missing outcome data |
Low |
Comment: 243 participants randomized; 242 participants analyzed.
Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO Score 7 and above. Time to WHO score 7 and above. 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). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO Score 7 and above. Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan 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). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO Score 7 and above. Time to WHO score 7 and above. Adverse events. Serious adverse events |
| Overall risk of bias |
Low |