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 |
Some concerns |
Quote: "Patients were randomized 1:1:1"
Comment: No information on randomization. No information on allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)"
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: Hospitalization or death. Mortality (D28). |
| Missing outcome data |
Some concerns |
Comment: 1678 participants randomized; 1484 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: not being treated (11 vs 12), withdrawal: patient decision (12 vs 15), lost to follow up (1 vs 4), withdrawal: sponsor request, not eligible/randomized in error (4 vs 2), withdrawal: physician decision (1 vs 0), adverse event (0 vs 1), lack of efficacy (0 vs 1), death (1 vs 0), unclear (72 vs 57). Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar proportion of missingness) Risk assessed to be some concerns for the outcomes: Hospitalization or death. Mortality (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: Hospitalization or death. Mortality (D28). |
| Selection of the reported results |
Some concerns |
Comment: The prospective registry was available (up to version dated September 1st, 2021).
MORTALITY 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 outcome: Mortality (D28). HOSPITALIZATION OR DEATH Composite outcome not pre-specified. Added in March 2021 version (retrospective) No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Hospitalization or death. |
| Overall risk of bias |
Some concerns |