| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concerns |
Quote: "Sequential randomisation for group allocation was performed at the research site with the computer software aid. The software generated a permuted block randomisation sequence in a 1:1 ratio and under no strata".
Comment: Allocation sequence random. No information on allocation concealment. Imbalances in baseline data appear compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "Only the lead researcher knew the allocation result; neither the rest of the collaborators nor the patients had any knowledge of the same."
Comment: Blinded study (patients and physicians). Data were analyzed using per-protocol analysis. As we are assessing the effect of assignment to intervention (intent-to-treat effect), this domain was evaluated as some concerns. |
| 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. Risk assessed to be some concerns for the outcome: Adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessors).
Risk assessed to be low for the outcomes: Mortality. 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. 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 |