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 trial statistician, not involved with patient enrollment or care, obtained a computer-generated randomization list (random.org)... The study treatment (A or B) was revealed to the pharmacist only after patients were registered in the system, ensuring proper concealment of the allocation sequence. The designated pharmacist at each study site was the only person aware of group allocation throughout the trial."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: "double-blind, placebo-controlled trial"
Comment: Blinded study (participants and personnel/carers). MORTALITY, HOSPITALIZED OR DEATH, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, ADVERSE EVENTS, 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). Hospitalization or death. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the viral negative conversion outcome. Of note, 44 vs 39 participants were excluded from the analysis post-randomization. 8 vs 11 were excluded for reasons other that missing data. 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 outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 475 participants randomized; 392 participants analyzed.
Data not available for nearly all participants randomized. No evidence that the result is not biased. Reasons: Discontinued Intervention (21 vs 18), Adverse events (6 vs 1), Hospitalized (5 vs 5), Missing primary outcome data (4 vs 4). Non-evaluable (1 vs 4) and Protocol deviation (7 vs 7) was not missing data and were accounted for in domain 2. Missingness could depend on the true value of the outcomes. Not likely that missingness depended on the true value of the outcome (similar proportions missing between arms, similar reasons for missingness). Risk assessed to be some concerns for the outcomes: Mortality (D28). Hospitalization or death. Clinical improvement (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Quote: "All outcomes were assessed by blinded investigators."
Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. Clinical improvement (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and the statistical analysis plan were available after contact with authors. The registry was available.
There is a difference in timepoints for the outcomes Viral negative conversion events and Adverse events between the report and the study registry. No information on whether the result was selected from multiple outcome measurements (timepoints). Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for outcomes: Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. HOSPITALIZATION OR DEATH 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 outcome: hospitalization or death. Data for the remaining outcomes were obtained from contact with 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 outcomes: Mortality (D28). . Clinical improvement (D28). WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |