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: “Participants were randomly assigned in a 1:1 ratio … via a web-based secure centralized system. An independent statistician provided a computer-generated assignment randomization list stratified by center and blocked with varying block sizes unknown to the investigators.”
Comment: Allocation sequence random. Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “Open-label study”
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 and biologics) were reported. The proportions of patients receiving antivirals and steroids were imbalanced between two arms (>10% absolute difference between the two arms) for steroids. This deviation could affect the outcome and was not balanced. Nevertheless, this domain was rated as some Concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. MORTALITY. CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS. Our analysis for the binary outcome is an 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). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT. TIME TO WHO SCORE 7 AND ABOVE. Participants were analyzed according to their randomized groups for the time-to-event outcome. Of note, 1 vs 0 participants were excluded from the analysis because of consent withdrawal which will be assessed in domain 3. Nevertheless, we consider the analysis appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns: Time to death. Time to clinical improvement. Time to WHO score 7 and above. |
| Missing outcome data |
Low |
Comment: 131 patients randomized; 130 patients analyzed.
One patient withdrew consent and asked data to be erased. No data were analyzed for this patient in accordance with European regulation. Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. MORTALITY, TIME TO DEATH Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. (TIME TO) WHO SCORE 7 AND ABOVE For this outcome, 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). Time to WHO score 7 and above. (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as "Discharge") 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). 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. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were available.
The authors provided some requested data. Other outcomes were 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. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO Score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |