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: “Randomization was done using an electronic web-based system with permuted blocks of 4 and allocation sequence concealment.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Single blinded (Outcomes Assessor)”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Biologics, antivirals and corticosteroids were reported and balanced between groups. Escalation/de-escalation of assigned anticoagulation regimens was balanced between groups. Hence, deviations did not arise because of the trial context. Data were analyzed using 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). Mortality (D60 or more). Clinical improvement (D28). Clinical improvement (D60 or more). WHO score 7 and above (D60 or more). Serious adverse events. Participants were analyzed according to their randomized groups for the time-to-event outcome. Of note, 23 vs 13 participants were excluded from the analysis post-randomization because they did not receive the drug (4 vs 0), did not meet eligibility criteria (1 vs 0 [which is acceptable]), and withdrew consent (18 vs 13 [which is related to missing data hence is assessed in domain 3]). This method was considered inappropriate to estimate the effect of assignment to intervention for this time-to-event 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 outcome: Time to death. |
| Missing outcome data |
Some concerns |
Comment: 598 patients randomized; 562 patients analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for exclusions: 31 withdrew consent; 4 did not receive at least 1 dose of the study treatment and 1 did not meet eligibility criteria (assessed in domain 2). Withdrawal of consent could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (same reasons for missingness and similar proportion of missingness) Risk assessed to be some concerns for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). WHO score 7 and above (D60 or more). Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). WHO score 7 and above (D60 or more). Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan, registry were available. However, both the protocol and SAP were dated November 20th, 2020 which is retrospective. There were prospective versions of the registry available (July 22nd and 26th, 2020 and August 2nd, 2020) but mortality and time to death outcomes were not pre-specified in those.
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 outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Outcome data acquired from contact with authors. 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: Clinical improvement (D28). Clinical improvement (D60 or more). WHO score 7 and above (D60 or more). Serious adverse events. |
| Overall risk of bias |
Some concerns |