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: "After obtaining informed written consent, they were randomly allocated to either treatment group A or group B in a 1:1 ratio. Block randomisation was done with variable random block sizes of 4, 6 and 8. A random allocation list of 120 patients was generated using the sealed envelope (an online block randomisation list generating software) and kept with a third person (not a part of the investigation team) prior to the commencement of the trial. Once an eligible study participant has provided consent for the trial, the investigation team doctor used to contact the concerned third person having the random allocation list over telephone to know the treatment group (A/B) for that particular patient. One of these two groups was the intervention group, and the other was the placebo group. However, up until the analysis of the data, this information was confined to the pharmacist dispensing the tablets."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Report: “double blind randomized placebo-controlled” "identical looking placebo tablets"
Registry: "Blinding/Masking: Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded" Comment: Blinded study (participants and personnel/carers). MORTALITY, CLINICAL IMPROVEMENT 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 outcome: Mortality (D28). Clinical improvement (D28). VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 25 vs 14 participants were excluded from the analysis post-randomization mostly due to missing data which is accounted for in domain 3; protocol violation (1 vs 1). Nevertheless, for this domain, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
High |
Comment: 115 patients randomized; 112 patients analyzed for mortality and clinical improvement; 76 patients analyzed for negative viral conversion.
MORTALITY, CLINICAL IMPROVEMENT Data available for all or nearly participants randomized. Of note, lost to follow-up (1 vs 0), protocol violation (1 vs 1) Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). VIRAL NEGATIVE CONVERSION Data not available for all or nearly participants randomized (32/57 vs 44/58). No evidence that the result is not biased. Reasons: lost to follow-up (1 vs 0), protocol violation (1 vs 1), discharged before day 6 (9 vs 3), sample not sent for unknown reason (2 vs 2), sample lost (9 vs 3), report inconclusive (3 vs 4), death (0 vs 1). Missingness could be related to the true value of the outcome. It is likely that missingness depended on the true value (based on differences in proportion of missing data between groups and reasons for missingness) Risk assessed to be high for the outcome: Incidence of viral negative conversion (D7). |
| 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). Incidence of viral negative conversion (D7). Clinical improvement (D28). |
| Selection of the reported results |
Some concerns |
Comment: The prospective trial registry was available (dated August 18th, 2020).
VIRAL NEGATIVE CONVERSION, CLINICAL IMPROVEMENT 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: Incidence of viral negative conversion (D7). Clinical improvement (D28). MORTALITY No timepoint was specified for the outcome Mortality. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcome: Mortality (D28). |
| Overall risk of bias |
High |