Trial NCT04542694
Publication Balykova L, Infektsionnye bolezn (2020) (published paper)
Primary outcome on the report: Time to clinical improvement – a decrease by 1 category in the assessment on the Categorical scale of clinical improvement of the World Health Organization…, and the number pf patients who achieved improvement by 2 categories

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: “Randomization was performed using the IWRS (Interactive web randomization system) integrated into the patient's electronic individual registration card.”
Comment: Allocation sequence random. Allocation sequence concealed.
Deviations from intervention
Low 		Comment: Unblinded study.
Deviations from intended intervention arising because of the study context:
There were 3 participants in the experimental group with deviations from the intervention (2 needed prohibited therapy and 1 protocol violation). These deviations represent 1.5% of the total sample size.
Administration of co-interventions of interest (antivirals, corticosteroids, biologics) were reported and balanced between groups.
Hence, deviations did not arise 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 low for the outcome: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 200 participants randomized; 200 participants analyzed.
Data available for all or nearly all participants (4 of 200 patients did not complete the study)
Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). Time to clinical improvement. 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.
Mortality and Viral negative conversion events are observer-reported outcomes not involving judgement. 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 outcomes: Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28).

Clinical improvement requires clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events. All these outcomes 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 outcomes: Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious Adverse events.
Selection of the reported results
Low 		Comment: The protocol and statistical analysis plan were available.
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). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events.
Overall risk of bias
Some concerns