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 |
Some concerns |
Quote: "Group allocation was performed at the research site through sequential randomization using
computer software. The software generated a permuted block randomization sequence in a 1:1 ratio with no underlying strata.".
Comment: Allocation sequence random. No information on allocation concealment. Imbalances in baseline data appear compatible with chance. |
| Deviations from intervention |
Low |
Quote: "The medical team in charge of the patients and treatment regimens was blinded.The lead researcher
was not blind to group allocation".
Comment: Blinded study (patients and physicians). 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 low concerns for the outcomes: Mortality (D28). Adverse Events. |
| Missing outcome data |
Some concerns |
Comment: 312 patients randomized; 243 patients analyzed.
Data unavailable for 22% of population (21% in Sulodexide arm vs 23% in placebo arm). Reasons reported were COVID-19 negative test result (8.9% vs 11%) [not due to missing data but eligibility criteria and type of analysis used]; lost to follow-up (7.6% vs 5.2%), voluntary abandoned trial (4.5% vs 7.1%) which were similar between groups. Lost to follow up and voluntary abandoned trial could be related to the true value of the outcome adverse events but it was not considered likely to. It could not be related to mortality because "If we failed to contact the participant during the follow-up period, and no data were available other than the initial inclusion survey, the patient was excluded from the final analysis after eliminating mortality as the cause of the inability to follow up." Risk assessed to be low for the outcome: Mortality (D28). Risk assessed to be some concerns for the outcome: Adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessors).
Measurement or ascertainment of outcome probably does not differ between groups. Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The study registry was available. The protocol and statistical analysis plan were not available.
Mortality was registered as reported in the paper. Adverse events were not registered. Mortality result was 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). No information on whether adverse events results were selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for outcome: Adverse events. |
| Overall risk of bias |
Some concerns |