Trial CTRI/2020/09/027535
Publication Ramachandran R, Int. J. Infect. Dis. (2021) (published paper)
Primary outcome on the report: Mild-asymptomatic patients: Time from randomization to nasopharyngeal swab negativity by two RT-PCR tests, for SARS-Cov-2 antigens, taken 24 hours apart; Moderate patients: time to improvement by one category from randomisation on the eight-category ordinal scale defined by WHO & average change in the ordinal scale from baseline

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 		Quotes: "Patients were randomized using Computerised randomization (Sequentially numbered opaque, sealed envelopes –SNOSE)" "Randomization and recruitment was administered by an independent clinical trial coordinator for true double-blinding"
Comment: Allocation sequence random.
Allocation sequence concealed.
Deviations from intervention
Low 		Quote: "double-blind" "All laboratory staff and doctors were also masked to treatment allocation and samples were identified by serial numbers" (report) "Participant and Investigator Blinded" (registry)
Comment: Blinded study (participants and personnel/carers).
Our analysis for the binary outcomes is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention.
For viral negative conversion, participants were analyzed according to their randomized groups for the outcome.
Of note, only participants asymptomatic or mild at baseline (67%, 82/123) were analysed for this outcome as planned in the protocol.
Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events.
Missing outcome data
Some concerns 		Comment: 132 participants randomized; 123 participants analyzed for mortality and safety; 82 participants analyzed for viral negative converison.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons: 6 (9%) vs 3 (4.5%) withdrawn consent / stopped drug on its own in intervention vs. control group. For viral negative conversion an additional 20 (30.3%) vs. 21 (31.8%) were missing due to pre-planned analysis of only asymptomatic and mild cases for this outcome, see domain 2.
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome reasons for missing data between arms were similar and proportions were not too different between groups.
Risk assessed to be some concerns for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). 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). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan, and trial registry (dated 1 September 2020) were available.
Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned.
The remaining outcomes were pre-specified.
Results were probably 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). Adverse events. Serious adverse events.
Overall risk of bias
Some concerns