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: "Randomization was centralized and performed electronically. Allocation sequences were generated in a 1:1 ratio by a computer-generated random number using a blocking schema; the range of block sizes remains confidential until the completion of the parent trial. Randomization was stratified by center and by use of mechanical ventilation at the time of inclusion."
Comment: The allocation sequence was random. The allocation sequence was concealed. |
| Deviations from intervention |
Low |
Protocol quote: "Placebo-controlled trial. Patients, investigators and care providers
will be blinded for the patient-arm."
Comment: Blinded study (participants and personnel/carers). 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 outcomes: Mortality (D28). WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 149 participants randomized, 149 participants analyzed.
Missing data for 1 participant that withdrew consent after randomization was imputed. Quote: "One patient withdrew consent; and for the primary outcome this patient was considered to have experienced treatment failure on day 21." Data available for all or nearly all participants randomized. Risk assessed to be low for outcomes: Mortality (D28). WHO score 7 and above (D28). Serious adverse events |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement of outcome probably does not differ between groups. Blinded study (outcome assessors). Risk assessed to be low for outcomes: Mortality (D28). WHO score 7 and above (D28). Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were available but retrospective. The registry was available and prospective versions were available.
Mortality was 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 outcome: Mortality (D28). WHO score 7 and above is a post-hoc outcome and not pre-specified. Safety outcomes were also 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 for WHO score 7 and above. No information on whether the trial was analyzed as pre-specified for serious adverse events. Risk assessed to be some concerns for the outcomes: WHO score 7 and above (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |