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: "Patients were assigned to stratified randomized treatments based on a central, computer-generated randomization scheme coordinated by an independent third party."
Quote: “conducted centrally by an independent third party to avoid selection bias.” Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "open-label"
Comment: Unblinded study. Deviations from intended intervention arising because of the study context: No participant cross-over. 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). Time to viral negative conversion. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 150 patients randomized; 147 patients analyzed
Data available for all or nearly all participants. Risk assessed to be low for the outcome: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. 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 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 the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Clinical improvement (defined as discharge) 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 outcomes. 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 the outcomes: Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The trial registry was available, but not the protocol or statistical analysis plan.
Outcomes pre-specified as reported. 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 outcome: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |