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 |
Report:
"Randomization was performed through an online web-based system using computer-generated random numbers and blocks of 2 and 4, unknown to the investigators, and was stratified by center. The group treatment was disclosed to the investigator only after all information regarding patient enrollment was recorded in the online system (eMethods in Supplement 3)." Supplement: "The randomization list was generated by the trial statistician, not involved in patient care or enrolment, using the R software (R Core Team, Vienna, Austria, 2020)" Comment: Allocation sequence random. Allocation sequence concealed. Baseline characteristics between intervention groups were comparable; any differences appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "open-label"
Comment: Unblinded study (participants and personnel/carers). No information on co-interventions of interest, antivirals and biologics, were reported. In the intervention arm, 1 patient received a corticosteroid other than dexamethasone. In the control arm, 52 patients received corticosteroids. This deviation was not balanced and could affect the outcome. 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. 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). Time to death. Clinical improvement (D28). WHO score 7 and above. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 299 participants randomized; 299 participants analyzed.
Quote: "All patients were included in the primary analysis. There was no loss to follow-up, and data on the primary outcome, mortality within 28 days, clinical status at day 15, ICU-free days at 28 days, and mechanical ventilation duration were available for all patients" Risk assessed to be low for outcomes: Mortality (D28). Time to death. 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 of outcome probably does not differ between groups. Unblinded study (outcome assessor). Mortality is an observer-reported outcome not involving judgement. For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of the intervention assignment. Risk assessed to be low for outcomes: Mortality (D28). Time to death. WHO score 7 and above (D28). Clinical improvement (defined as discharge) reflects decisions made by the intervention provider. 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 the outcomes: Clinical improvement (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were available but the version was retrospective. The prospective registry was utilized (up to its April 13th version).
Mortality and WHO score 7 and above outcomes reported as prespecified. 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 outcomes: Mortality (D28). WHO score 7 and above (D28). All other outcomes were not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Time to death. Clinical improvement (D28). Adverse events. Serious adverse events |
| Overall risk of bias |
Some concerns |