Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial

Background The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed healthcare systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19. Methods The ACT outpatient, open-label, 2 x 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0 center dot 6 mg twice daily for 3 days and then 0 center dot 6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing. Findings Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0 center dot 1%) of 3881 for major thrombosis, 123 (3 center dot 2%) of 3881 for hospitalisation, and 23 (0 center dot 6%) of 3881 for death; 66 (3 center dot 4%) of 1939 patients allocated to colchicine and 65 (3 center dot 3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1 center dot 02, 95% CI 0 center dot 72-1 center dot 43, p=0 center dot 93); and 59 (3 center dot 0%) of 1945 of patients allocated to aspirin and 73 (3 center dot 8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0 center dot 80, 95% CI 0 center dot 57-1 center dot 13, p=0 center dot 21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1 center dot 8%] of 1939 vs 27 [1 center dot 4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1 center dot 6%] vs 31 [1 center dot 6%]) and none that led to discontinuation of study interventions.

Automated summary

The ACT outpatient trial aimed to evaluate the effectiveness of colchicine and aspirin in preventing disease progression in community patients with COVID-19. The results showed no significant difference in the occurrence of major outcomes, such as hospitalization or death, between the colchicine and aspirin treatment groups compared to the control groups. The study also found that the colchicine group had more serious adverse events, but none of them led to discontinuation of the study interventions. There was no significant increase in serious adverse events in the aspirin group compared to the control group.