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: “Permuted block randomization sequence (variable block size of 3 and 6) was generated by a trial-independent statistician using R software version 3.6.1”
Quote:"the allocated sequence was concealed all through the study until the blinded analysis was done. 1.The randomization was performed centrally. 2.The allocation sequence was sequentially numbered and preserved in sealed envelope which was retained by the independent statistician. 3.In addition, coded drug containers were provided to the trial site. Comment: Allocation sequence random. Allocation sequence concealed |
| Deviations from intervention |
Low |
Quote: “randomized, double-blind, placebo-controlled trial”
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 time-to-event outcome. Of note, 1 vs 2 vs 1 participants were excluded from the analysis post-randomization for reasons related to missing data. Nevertheless, for this domain, this method was considered probably appropriate to estimate the effect of assignment to intervention for this time-to-event outcome. Risk assessed to be low for 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. |
| Missing outcome data |
Low |
Comment: 72 patients randomized; 68 patients analyzed.
Data not available for all or nearly all participants. No evidence that the result is not biased. Reasons for missingness: withdrew consent. This is a documented reason unrelated to the outcome. Missingness could not depend on the true value of the outcome. 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 |
Low |
Quote: “randomized, double-blind, placebo-controlled trial”
Comment: Outcome assessor was likely blinded. Risk assessed to be low for the outcomes: Mortality. Viral negative conversion. Time to viral negative conversion. Score WHO 7 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The registry was available.
Data on all outcomes except time to viral negative conversion were requested from the authors. 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). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. Time to viral negative conversion was not pre-specified in the registry. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for outcome: Time to viral negative conversion. |
| Overall risk of bias |
Some concerns |