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: "Eligible patients underwent treatment allocation and concealment through a randomization program (REDCap). Randomization was performed in variable size blocks of 3, 6, 9 and 12 participants and stratified by clinical site. This list will remain hidden from both the doctors and nurses in charge of the assistance of each participant (protocol)”
Comment: Allocation sequence random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “Both participants and the clinical research team remained blind to the treatment assignment.”
Comment: Blinded study (participants and personnel/carers). Data for the binary outcomes were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Participants were analyzed according to their randomized groups for the outcome for time-to-event outcomes. Of note, 1 participant randomized to the placebo group did not receive it sue to withdrawn consent. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. 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 (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 334 participants randomized; 333 participants analyzed.
Data available for all or nearly all participants randomized. 1 patient withdrew consent and did not receive placebo. 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 (D28). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Quote: "double blind, placebo-controlled"
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Outcome assessor was probably blinded. 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 (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan and prospective registry were available.
Data analyzed and presented as pre-specified for all outcomes except Time to clinical improvement. Clinical improvement events were obtained via contact with authors. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as prespecified. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). WHO score 7 and above. Adverse events. Serious adverse events. Time to clinical improvement (time to improvement of 2 categories in the ordinal scale or hospital discharge within 30 days) was not specified in the protocol or registry. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for outcome: Time to clinical improvement. |
| Overall risk of bias |
Some concerns |