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: “Post-consent, patients were randomly assigned by an unblinded enrollment research nurse in a 2:2:2:1 ratio in blocks to one of four groups using a computer-generated randomization schedule provided by the study’s statistician (without stratification). Allocation concealment was ensured by having only the enrollment research nurse be unblinded and with maintaining confidentiality of the allocation.”
Comment: Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Low |
Quote: “quadruple-blinding (patient, clinical nurse/physician, study nurse, investigators)”
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. Risk assessed to be low for the outcomes: Mortality (D60 or more). |
| Missing outcome data |
Some concerns |
Comment: 13 participants randomized; 12 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 1 patient in the placebo group withdrew after randomization (was not assessed in ROB2) Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Mortality (D60 or more). |
| 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 (D60 or more). |
| Selection of the reported results |
Low |
Comment: The registry was available (dated March 27, 2020).
Outcome pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcome: Mortality (D60 or more). |
| Overall risk of bias |
Some concerns |