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 performed with a centralized, computer-generated allocation sequence stratified by trial site, age below 70 years, and use of invasive mechanical ventilation at the time of screening.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Low |
Quote: “Quadruple blinding (Participant, Care Provider, Investigator, Outcomes Assessor). Treatment assignments were concealed from patients, clinicians, investigators, trial statisticians, the DSMC and the Management Committee.”
Comment: Blinded study (participants and personnel/carers). MORTALITY, SERIOUS ADVERSE EVENTS 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. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Serious adverse events. TIME TO DEATH Participants were analyzed according to their randomized groups for the outcome. Of note, 17 vs 20 participants were excluded from the analysis post-randomization due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be low for the outcomes: Time to death. |
Missing outcome data |
Low |
MORTALITY D28
Comment: 1000 participants randomized; 971 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 Comment: 1000 participants randomized; 963 participants analyzed. Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to death. SERIOUS ADVERSE EVENTS Comment: 1000 participants randomized; 982 participants analyzed for safety outcomes. Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: 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). Serious adverse events. Time to death. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and prospective registry (August 12, 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). Serious adverse events. Time to death. |
Overall risk of bias |
Low |