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: “A centralized, web-based automated randomization system was used to conceal allocation”
Comment: Allocation sequence random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “open-label”
Comment: Unblinded study. No participant cross-over. Administration of co-interventions of interest reported and balanced between groups: antivirals, corticosteroids, biologics. Overall, there were no deviations that arose because of the trial context. Data were analyzed appropriately to estimate the effect of assignment to intervention; participants analyzed according to their randomized assignment. Of note, 37 vs 44 patients were excluded from the analysis. This will be taken into account in ROB domain 3. Risk assessed to be low for outcome: Mortality (D28). |
| Missing outcome data |
Low |
Comment: 740 patients randomized; 659 patients analyzed.
Data available for < 95% of population. No evidence that the result is not biased. Patients excluded from analysis: 37 patients did not discontinue use of ACEI or ARB as randomized; 44 patients did not continue use of ACEI or ARB as randomized. These were due to a single site with serious Good Clinical Practice violations (34 vs 39), duplication or randomization error (2 vs 1), COVID-19 diagnosis not confirmed (1 vs 3) and lack of informed consent (0 vs 1). Overall, these exclusions could not depend on the true value of the outcome. Risk assessed to be low for the outcome: Mortality (D28). |
| Measurement of the outcome |
Low |
Quote: "blinded end-point assessment"
Comment: Method of measuring 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 outcome: Mortality (D28). |
| Selection of the reported results |
Low |
Comment: The protocol and registry were available.
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). |
| Overall risk of bias |
Low |