For patients hospitalized with COVID-19, use of colchicine and the combination of rivaroxaban and aspirin do not prevent disease progression or death, according to a study in The Lancet Respiratory Medicine.
Researchers reported results from the Anti-Coronavirus Therapies (ACT) inpatient trial (ClinicalTrials.gov Identifier: NCT04324463) that evaluated the use of colchicine and the combination of rivaroxaban and aspirin in patients hospitalized with COVID-19.
Eligible participants were symptomatic with laboratory-confirmed COVID-19 disease, aged at least 18 years, and within 72 hours of admission to a hospital or worsening clinically if already hospitalized.
The patients were assigned randomly to receive colchicine (1.2 mg followed by 0.6 mg 2 hours later and then 0.6 mg twice daily in tablet form) or usual care for 28 days. In a second assignment, patients were randomly assigned to received rivaroxaban (2.5 mg twice daily in tablet form) and aspirin (100 mg once daily in tablet form) or usual care for 28 days.
The primary outcome for the colchicine vs control (ie, usual care) group was a composite of need for high-flow oxygen, mechanical ventilation, or death. The primary outcome for the combination of rivaroxaban and aspirin vs control group was the composite of major thrombosis, need for high-flow oxygen, mechanical ventilation, or death. Outcomes were assessed at day 45.
The researchers also performed a literature search to identify trials of intensified anticoagulant therapy in patients hospitalized with COVID-19 to contextualize their results.
The trial was conducted at 62 sites in 11 countries from October 2, 2020, and February 10, 2022. A total of 2611 patients were included for the analysis of colchicine (n = 1304) vs control (n = 1307), and 2119 patients were included in the analysis of rivaroxaban and aspirin (n = 1063) vs control (n = 1056). Participants in the analysis of colchicine vs control had a mean (SD) age of 56.1 (16.3) years and were 59.7% male. Participants in the analysis of the combination of rivaroxaban and aspirin vs control had a mean (SD) age of 54.9 years (15.9) and were 58.6% male.
Colchicine did not significantly decrease the primary outcome of high-flow oxygen, ventilation, or death compared with usual care (368 [28.2%] events in 1304 participants vs 356 [27.2%] events in 1307 participants, respectively; hazard ratio [HR] 1.04; 95% CI, 0.90-1.21; P =.58) or the secondary outcome of high-flow oxygen, ventilation, or respiratory death (343 [26.3%] vs 323 [24.7%], respectively; HR 1.07; 95% CI, 0.92-1.25; P =.38).
Likewise, the combination of rivaroxaban and aspirin did not significantly lower the primary outcome compared with usual care (281 [26.4%] events in 1063 participants vs 300 [28.4%] events in 1056 participants, respectively; HR 0.92; 95% CI, 0.78-1.09; P = .32) or the secondary outcome (269 [25.3%] vs 280 [26.5%], respectively; HR 0.95; 95% CI, 0.80-1.12, P = .53).
In the safety analysis, no increase was observed in serious adverse events with colchicine vs usual care (87 events [6.7%] of 1304 vs 90 [6.9%] of 1307) or with rivaroxaban and aspirin vs control (85 events [8.0%] vs 91 [8.6%]).
The literature review found a total of 9 controlled trials (including the ACT inpatient trial) of intensified anticoagulation using therapeutic or intermediate dose unfractionated or low molecular weight heparin in patients hospitalized with COVID-19. From an overall 7503 patients, 92 (2.4%) of 3798 who received intensified anticoagulation vs 159 (4.3%) of 3705 who received the control treatment had venous thromboembolism (risk ratio [RR] 0.57; 95% CI, 0.45-0.73; Pheterogeneity =.20). Of 7640 patients, death occurred in 691 (17.7%) of the 3893 patients who received intensified anticoagulation vs 693 (18.5%) of the 3747 patients who received the control treatment (RR 0.94; 95% CI, 0.80-1.10; Pheterogeneity= .027).
Study limitations include the open-label design and the fact that the ACT inpatient trial had been conducted when different SARS-CoV-2 viral variants had emerged. In addition, an increasing proportion of patients over time had been vaccinated before study entry, which may have affected the treatment response.
“The lack of evidence of benefit of colchicine and of the combination of rivaroxaban and aspirin suggests that these treatments should not be used for the treatment of patients hospitalized with COVID-19,” the investigators concluded.
Disclosure: This research was funded in part by Bayer. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. Published online October 10, 2022. doi:10.1016/S2213-2600(22)00298-3