Covid-19 Living Data

Trial CTRI/2020/06/026087
Publication Pandit A, Int J Infect Dis (2021) (published paper)
Primary outcome on the report: Clinical status assessed on day 15 on a WHO 7-point ordinal scale consisting of the following categories: 1, not hospitalized, no limitations of activities; 2, not hospitalized, limitation on activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, on non-invasive ventilation or high flow oxygen devices; 6, hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 7, death

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	Some concerns	Quote: “Randomization was generated using SAS1 software (Version 9.4).” Comment: Allocation sequence random. No information on allocation concealment.
Deviations from intervention	Some concerns	Quote: “Open-label” Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: Biologics, antivirals and corticosteroids. Hence, no information on whether deviations arose because of the trial context. Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Missing outcome data	Low	Comment: 40 participants randomized; 40 participants analyzed for safety outcomes; 39 participants analyzed for all other outcomes. Data available for all or nearly all participants randomized. 1 participant excluded due to withdrawn consent. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Measurement of the outcome	Some concerns	Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor). MORTALITY, VIRAL NEGATIVE CONVERSION Mortality and viral negative conversion are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). WHO SCORE 7 AND ABOVE For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcome: WHO score 7 and above (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). ADVERSE and SERIOUS ADVERSE EVENTS Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes and can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events.
Selection of the reported results	Some concerns	Comment: The protocol and statistical analysis plan were not available. The prospective version of the trial registry was not accessible, nor was the capability to see the modifications that had been made. VIRAL NEGATIVE CONVERSION, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. MORTALITY Mortality outcome was not pre-specified, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. 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 outcome: Mortality (D28).
Overall risk of bias	Some concerns