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 randomized using the RedCap, a secure web application for building and managing electronic case report forms".
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "open-label, phase II trial".
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over (3 intervention participants (11%) discontinued treatment during the first 5 days). Administration of co-interventions of interest (biologics, antivirals and corticosteroids) 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. Participants were analyzed according to their randomized groups for the outcome. Risk assessed to be low for the outcomes: Mortality (D28), Mortality (D60 or more), Time to death, Clinical improvement (D28), Clinical improvement (D60 or more), Time to clinical improvement, WHO score 7 and above (D28), WHO score 7 and above (D60 or more), Adverse events, and Serious adverse events. |
| Missing outcome data |
Low |
Comment: 55 participants randomized; 55 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28), Mortality (D60 or more), Time to death, Clinical improvement (D28), Clinical improvement (D60 or more), Time to clinical improvement, WHO score 7 and above (D28), WHO score 7 and above (D60 or more), Adverse events, and 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, TIME TO DEATH Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28), Mortality (D60 or more), and Time to death. 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 outcomes: WHO score 7 and above (D28) and WHO score 7 and above (D60 or more). (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as patients who achieved a clinical status ≤ 3 on an eight-point ordinal scale) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28), Clinical improvement (D60 or more), and Time to clinical improvement. ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which 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, and Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan, and registry were available (dated April 3, 2020).
Mortality and adverse events 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: Mortality (D28), Mortality (D60 or more), Time to death, Adverse events, and Serious adverse events. The 8-point ordinal scale upon which the outcome clinical improvement and WHO score 7 and above are based was added to the trial protocol during follow up after enrollment of the last participant, but before termination of the study. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28), Clinical improvement (D60 or more), Time to clinical improvement, WHO score 7 and above (D28), and WHO score 7 and above (D60 or more). |
| Overall risk of bias |
Some concerns |