| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concerns |
Quote: “Randomized, double-blind trial”
Comment: No information on allocation sequence generation. No information on allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Randomized, double-blind trial”
Comment: Blinded study (participants, personnel/carers). Participants were analyzed according to their randomized groups for the outcome. Of note 18 participants (unclear distribution/proportion between arms) were excluded from the analysis post-randomization due to study medication not delivered at patient home (11) and eligibility issues/condition declined before delivery of study medication (7). Nevertheless, we consider this method appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Quote: "At the time of database lock and unblinding on January 20, 2021, vital and primary endpoint event status were available for all except for 93 patients (97.9%)."
Comment: 4506 patients randomized; 4488 patients analyzed for efficacy; 4412 analyzed for safety. Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Quote: "double-blind, placebo-controlled"
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). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The trial registry was available.
Mortality outcome pre-specified in the registry. 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). Safety outcomes were not pre-specified in the registry. No information on whether the results were selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcome: Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |