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 |
Report: "A computer-generated permuted block randomization with mixed block size was used to randomize the participants in a 1:1:1:1 ratio to four groups: group A (atorvastatin), group B (aspirin), group C (combination of aspirin and atorvastatin), and group D (control)."
Registry: "Method of concealment: Sequentially numbered, sealed, opaque envelopes" 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) Deviations from intended intervention arising because of the study context: 3 (Atorvastatin group) vs 2 (Aspirin group) participants received both drugs. 5 participants (Aspirin group) received Atorvastatin only. 7 received only Atorvastatin and 4 only Aspirin (Atorvastatin+Aspirin group) Administration of co-interventions of interest, antivirals, biologics and corticosteroids, were reported and balanced among arms. This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. MORTALITY, WHO SCORE 7 AND ABOVE Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). WHO score 7 and above (D28). TIME TO WHO SCORE 7 AND ABOVE Participants were analyzed according to their randomized groups for the outcome. Of note, 3 vs 4 vs 4 vs 7 participants were excluded from the analysis post-randomization due to ineligibility. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be some concerns for the outcome: Time to WHO score 7 and above. |
| Missing outcome data |
Low |
Comment: 900 participants randomized; 882 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). (TIME TO) WHO SCORE 7 AND ABOVE For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: WHO score 7 and above (D28). Time to WHO score 7 and above. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were not available. The prospective version of the registry (dated July 25th, 2020) was not accessible, however the updated version (dated March 24th, 2021) revealed which topics were modified and 'Outcomes' were not among them. Hence this version of the registry was considered appropriate and consulted.
Outcomes pre-specified. 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). WHO score 7 and above (D28). Time to WHO score 7 and above. |
| Overall risk of bias |
Some concerns |