Randomized Controlled Trial
Study population and setting
The COLCORONA trial was a phase 3, double-blind, multicenter randomized controlled trial that compared treatment with oral colchicine (0.5 mg twice a day for 3 days and subsequently once a day for 27 more days) against placebo. It enrolled 4488 participants (n=2235 colchicine arm, n=2253 placebo arm) between March 23 and December 22, 2020 in Brazil, Canada, Greece, South Africa, Spain, and the United States. Participants were eligible if they had been diagnosed with COVID-19 within 24 hours of enrollment but were not being considered for immediate hospitalization, and were either >70 years old or >40 years old with at least one of: BMI > 30 kg/m2, diabetes, systolic blood pressure > 150 mmHg, known respiratory or heart disease, fever > 38.4 deg C, dyspnea, had more than one low cell count, or a high neutrophil count with lymphocytopenia. Eligible participants were 1:1 randomized in block sizes of six to 0.5 mg of colchicine twice daily for three days and then daily for 27 days or a matching placebo. The primary endpoint was a composite of death or need for hospitalization due to COVID-19 within 30 days after randomization, and the one planned subgroup analysis included the participants (n=2075 colchicine, n=2084 placebo) who enrolled after a positive PCR test.
Summary of Main Findings
In an intention-to-treat analysis, 104/2235 (4.7%) patients treated with colchicine had a primary endpoint event (death and/or hospitalization due to COVID-19), compared to 131/2253 (5.8%) patients in the placebo group (OR 0.79; 95%CI 0.61,1.03). Subgroup analysis of only patients with PCR-confirmed COVID-19 (n=2075 colchicine arm, n=2084 placebo arm) revealed a reduction in primary endpoint event among patients treated with colchicine (4.6% vs. 6.0% placebo; OR 0.75; 95%CI 0.57,0.99). Post-hoc analyses reveal a significant reduction in the rate of hospitalization (OR 0.75; 95%CI 0.57,0.99) but not in the mortality rate (OR 0.56; 95%CI 0.19,1.66). Stratification of the patients by any of the aforementioned risk factors showed nonsignificant decreases in the primary endpoint rate. Participants in the colchicine arm were more likely to have gastrointestinal adverse effects than those in the placebo arm (23.9% vs 13.8%).
The study population consisted of patients with above-average risk for severe COVID-19 but who were not immediately considered for hospitalization, which describes a sizeable proportion of COVID-19 cases. The double-blinded, randomized participant allocation reduced the risk of unmeasured confounding, selection bias, and analytical bias. Lastly, the enrolled patients were 53.9% women, which is more representative of the population at large, compared to trials with a heavy male-predominant population.
The study only recruited 75% of the anticipated number of patients, which left the study slightly underpowered for the composite primary endpoint of death or hospitalization due to COVID-19. Furthermore, they did not utilize a stratified randomization scheme or condition on covariates associated with the outcome, both of which could have increased power and mitigated the fact that they ended the study early. Also, colchicine treatment was only assessed with a 30-day course, and endpoints were measured only up to 30 days from randomization, which limits the ability to make conclusions about shorter courses of treatment, longer-term outcomes of colchicine treatment, or the potential impact of colchicine on COVID-19 symptoms that linger beyond the initial infection. Finally, the majority of participants lived in Canada or the United States, potentially limiting generalizability to regions outside of North America.
This study suggests that oral colchicine can be used as an effective treatment in preventing death or hospitalization among individuals with an elevated risk profile for severe COVID-19 shortly after a diagnosis.
This review was posted on: 19 July 2021