For a study, researchers sought to see if antiplatelet medication improved outcomes in critically sick patients with COVID-19. In an ongoing adaptive platform experiment (REMAP-CAP) assessing numerous therapies across many therapeutic domains, 1,557 critically ill adult patients with COVID-19 were enrolled from 105 locations in 8 countries between October 30, 2020, and June 23, 2021, and were followed up for 90 days (final follow-up date: July 26, 2021). Patients were randomly assigned to one of three groups: open-label aspirin (n = 565), a P2Y12 inhibitor (n=455), or no antiplatelet medication (n=529). The interventions, which were in addition to anticoagulant thromboprophylaxis, were continued in the hospital for a maximum of 14 days. The primary end criterion was organ support–free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, with a score ranging from 1 for any death in hospital (censored at 90 days) to 22 for survivors who did not receive organ support. There were 13 secondary outcomes, including discharge survival and significant bleeding lasting 14 days. A Bayesian cumulative logistic model was used for the primary analysis. An OR larger than one indicated increased survival, more organ support–free days, or both. Efficacy was defined as having a posterior probability of higher than 99% for an OR greater than one. Futility was defined as having a larger than 95% posterior chance of having an OR less than 1.2 versus control. Intervention equivalence was defined as a better than 90% chance that the OR (when compared to each other) for two non-control treatments was between 1/1.2 and 1.2.
At an adaptive analysis, the aspirin and P2Y12 inhibitor groups satisfied the established criteria for equivalency and were statistically pooled for further analysis. Enrollment was halted after the predefined futility threshold for the pooled antiplatelet group vs control was satisfied. Around 8 of the 1,557 severely ill patients who were randomized withdrew their permission, leaving 1,549 to finish the experiment (median age, 57 years; 521 [33.6%] female). In both the antiplatelet and control groups, the median number of organ support–free days was 7 (IQR, 1 to 16) (median-adjusted OR, 1.02 [95 %credible interval CrI, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge in the antiplatelet and control groups were 71.5% (723/1011) and 67.9% (354/521), respectively (median-adjusted OR, 1.27 [95% CI, 0.99-1.62]; adjusted absolute difference, 5% [95% CI, 0.2% to 9.5%]; 97% posterior probability of efficacy). The median number of organ support–free days among survivors was 14 in both groups. Major bleeding occurred in 2.1% of patients in the antiplatelet and 0.4% of patients in the control groups, respectively (adjusted OR, 2.97 [95% CI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CI, 0.1% -2.7%]; 99.4% probability of harm). Treatment with an antiplatelet agent, compared to no antiplatelet agent, showed a modest chance of improving the number of organ support–free days within 21 days in critically sick patients with COVID-19.
Reference:jamanetwork.com/journals/jama/fullarticle/2790488
