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: “Enrolled participants were randomized using permuted blocks of randomly varying sizes (2, 4, or 6) stratified by site and age (>=60 or <60 years). A central randomization website generated treatment allocations in a 1:1 ratio.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).” "All participants and study personnel were blinded except statisticians preparing the randomization and investigational pharmacists”
Comment: Blinded study (participants and personnel/carers) Our analysis for the binary outcomes 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). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 205 participants randomized; 202 participants analyzed.
Of note 1 vs 2 participants withdrew consent Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). |
| 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). Clinical improvement (D28) |
| Selection of the reported results |
Some concerns |
Comment: The prospective trial registry was available (March 17, 2020).
MORTALITY 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). Mortality (D60 or more). CLINICAL IMPROVEMENT Outcome not pre-specified No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Clinical improvement (D28) |
| Overall risk of bias |
Some concerns |