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 performed using central web-based systems"
Comment: Allocation sequence probably random. Allocation sequence concealed.
Minor imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "open-label"
Comment: Unblinded trial (participants and personnel/carers) Deviations from intended intervention arising because of the study context: The comparison was therapeutic-dose anticoagulation with heparin versus usual care prophylactic anticoagulation. Thus both arms received anticoagulation, with some in each group receiving similar regimens. 11.3% of the intervention group did not received prophylactic anticoagulation. 6.1% of the control group received the intervention. No information on administration of co-interventions of interest: antivirals and corticosteroids. Biologics Hence, deviations did not arise because of the trial context. 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). Clinical improvement (D28). |
| Missing outcome data |
Some concerns |
Comment: 1207 participants randomized; 1098 participants analyzed. Data not available for all or nearly all participants randomized; No evidence that the result is not biased. Reasons for missing data: 10 vs 13 withdrew consent, 2 vs 3 outcome not available, 45 vs 36 SARS-CoV-2 not confirmed. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (same reasons and equal proportion of missing data between arms). Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). |
| 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge from hospital) requires clinical judgement and could be affected by knowledge of intervention receipt. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). |
| Selection of the reported results |
Some concerns |
Comment: The protocol (prospective core protocol dated July 10th, 2019 and retrospective Therapeutic Anticoagulation Domain-Specific Appendix Version 2.0 dated June 24th 2020), statistical analysis plan (retrospective, dated 5th January), several registries (retrospective) were available.
The protocol was retrospective and the prospective versions of the registries did not specify discharge outcome nor the major thrombotic events or death outcome, from which mortality at day 28 outcome was extracted. 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). Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |