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: "Patients were randomised through a computerised system (RedCap®, Vanderbilt University, USA, Version 10.6.13) according to a 2:1 allocation scheme stratified by study site using randomly selected block sizes of 6 or 9."
Comment: Allocation sequence random Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “Open-label"
Comment: Unblinded study (participants and personnel/carers) MORTALITY. SERIOUS ADVERSE EVENTS. 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). Serious adverse events. TIME TO DEATH Participants were analyzed according to their randomized groups for the outcome. Of note, 6 participants in the intervention arm were excluded from the analysis post-randomization because 5 were not treated and no data was available after randomization and 1 was wrongfully diagnosed with COVID. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcomes: Time to death. |
| Missing outcome data |
Some concerns |
Comment: 489 participants randomized; 483 participants analyzed; 39 (8%) missing data.
MORTALITY, SERIOUS ADVERSE EVENTS Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 21 vs 10 lost to followup, 4 vs 1 left hospital, 3 vs 0 other. 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 (D28). Serious adverse events. TIME TO DEATH Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 16 vs 10 lost to followup, 4 vs 1 left hospital, 2 vs 0 other. 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: Time to death. |
| 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. Unblinded study (outcome assessor) MORTALITY, TIME TO DEATH Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which 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 outcomes: Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan, and registry (dated June 12, 2020) were retrospectively available.
MORTALITY The registry was retrospective, 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 outcome: Mortality (D28). TIME TO DEATH, SERIOUS ADVERSE EVENTS No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Time to death. Serious adverse events. |
| Overall risk of bias |
Some concerns |