ABSTRACT
Background: Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus 150mg aspirin once daily until discharge using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0.96; 95% confidence interval [CI] 0.89-1.04; p=0.35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1.06; 95% CI 1.02-1.10; p=0.0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0.96; 95% CI 0.90-1.03; p=0.23). Aspirin use was associated with an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in clinically significant bleeding of 0.6% (SE 0.2%). Interpretation: In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death but was associated with a small increase in the rate of being discharged alive.