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: "The randomization grid was designed via the REDCap database and based on 25% of anticipated enrolled patients in each of the 4 groups. An automatically created link in REDCap randomized the patient to the supplement group based on the randomization grid."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "Open-label"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No information on participant cross-over. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation arose because of the trial context. 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). Adverse events. |
| Missing outcome data |
Some concerns |
Comment: 214 participants randomized; 214 participants analyzed for mortality outcome; 196 patients analyzed for adverse events.
Data available for all or nearly all participants randomized for mortality. Risk assessed to be low for the outcome: Mortality (D28). Data not available for all or nearly all participants randomized for adverse events. Reasons for missing data: not reported. No information on whether missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (equal proportion of missing data among arms). Risk assessed to be some concerns for the outcome: Adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). The authors reported on adverse events that contain clinically-detected events. All these outcomes can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcome: Adverse events |
| Selection of the reported results |
Low |
Comment: Protocol & statistical analytical plan & registry available:
Adverse events were pre-specified. Mortality outcome was not pre-specified, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably 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). Adverse events. |
| Overall risk of bias |
Some concerns |