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: "After confirming eligibility and obtaining informed consent designated individuals at the clinical sites used a web-based randomization application to verify eligibility to obtain a study identification (SID) number for blinded agent/matching placebo. This “prescription” was sent to the site pharmacy. The site pharmacist used a web-based pharmacy application to determine which agent/placebo the SID corresponds to. The pharmacist was unblinded and prepared the infusion bag for the patient"
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “The following people were masked to treatment allocation: the patient, the patient's family, clinical personnel caring for the patient, investigators in the trial, study personnel who collected data, and all outcome assessors.”
Comment: Blinded study (participants and personnel/carers) 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. For the Time to all-cause mortality outcome, participants were analyzed according to their randomized groups for the outcome. Of note, 2 vs 5 vs 3 participants were excluded from the analysis post-randomization because they did not receive the drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 546 participants randomized; 532 to 536 participants analyzed.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). WHO score 7 and above (D28). Adverse events. Serious 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. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D60 or more). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry (dated August 6, 2020) were available.
Outcome 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 (D60 or more). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |