|Bias||Author's judgement||Support for judgement|
"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)."
"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||
|Comment: Unblinded study.
In the intervention arm, 25 deviations from protocol in the intervention arm (16.55%); 1 patient received a corticosteroid other than dexamethasone. In the control arm, 52 patients received corticosteriods, of which 14 were protocol deviations (9.45%).
No information on co-interventions of interest, antivirals, anticoagulants and biologics, were reported.
Deviations might have arisen because of the experimental context and are likely to have affected the outcome.
Difference in between-group deviations <10%
Appropriate analysis method was used (intention-to-treat)
|Missing outcome data||
|Comment: 299 patients randomized; 299 patients 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. Time to death. Incidence of clinical improvement. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Adverse events. Serious adverse events.
|Measurement of the outcome||
|Comment: Appropriate method of outcome measurement.
Measurement of outcome does not differ between groups.
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. Time to death. Incidence of WHO score 7 and above.
Clinical improvement (defined as discharge) and incidence of WHO score 6 and above reflects decisions made by the intervention provider. Furthermore, adverse events and serious adverse events reported contain both clinically- and laboratory-detected events. Assessment of these outcomes could possibly be influenced by knowledge of the intervention assignment but we did not consider this likely to have happened in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Incidence of clinical improvement. Incidence of WHO score 6 and above. Adverse events. Serious adverse events.
|Selection of the reported results||
|Comment: The protocol and statistical analysis plan were available. Outcomes reported as prespecified.
Risk assessed to be low for outcomes: Mortality. Time to death. Incidence of clinical improvement. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Adverse events. Serious adverse events
|Overall risk of bias||