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: “Before the onset of the trial, a random sequence was created using a web-based randomization software using 4, 6 and 8 block sizes and a list length for 662 treatments. The randomization sequence and the allocation concealment were performed remotely from the patient recruiting centers and it was not stratified by site.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Double-blind. The local investigators who were directly involved with patient care, other healthcare providers, and patients were kept blinded to the group assignments until all patients completed the 28-day post-randomization period and the data was locked. Pre-packing of tablets of either active or placebo group was manufactured to appear identical.”
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). Time to death. Clinical improvement (D28). Adverse events. |
| Missing outcome data |
Low |
Comment: 645 participants randomized; 645 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Probably blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and prospective registry (dated January 28th 2021) were available
Outcomes 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). Time to death. Clinical improvement (D28). Adverse events. |
| Overall risk of bias |
Low |