Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
PLOS ONE, doi:10.1371/journal.pone.0277790
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment for the extensive release of acute inflammatory mediators induced by hyperactive and inappropriate immune responses is very limited. Many antiinflammatory drugs with variable efficacies have been investigated. Colchicine inhibits interleukin 1 beta (IL-1β) and its subsequent inflammatory cascade by primarily blocking pyrin and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) activation. Therefore, this cheap, widely available, oral drug might provide an added benefit in combating the cytokine storm in COVID-19. Here, we sought to determine whether adding colchicine to other standards of care could be beneficial for moderate COVID-19 pneumonia in terms of the requirement for advanced respiratory support and mortality.
Methods and findings This blinded placebo-controlled drug trial was conducted at the Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 300 patients with moderate COVID-19 based on a positive RT-PCR result were enrolled based on strict selection criteria from June 2020 to November 2020. Patients were randomly assigned to either treatment group in a 1:1 ratio. Patients were administered 1.2 mg of colchicine on day 1 followed by daily treatment with 0.6 mg of colchicine for 13 days or placebo along with the standard of care. The primary outcome was the time to clinical deterioration from randomization to two or more points on a seven-category ordinal scale within the 14 days post-randomization. Clinical outcomes
Subgroup analysis Subgroup analysis of sex (male vs. female), age (18-40 years, 41-60 years, > 60 years), comorbidities (diabetes mellitus, hypertension, asthma, and COPD), and duration of symptoms before enrolment (10 days or less vs. more than 10 days) did not reveal any credible subgroup effects (S1 Fig).
Additional analysis The outcomes were analyzed on day 28 of follow-up. Two-point deterioration at the 28-day follow-up was found in 13 (8.9%) patients in the placebo group and 4 (2.7%) patients in the colchicine group. The rate of deterioration was significantly lower in colchicine group, with a hazard ratio [95%CI] of 0.29 [0.098-0.917], (P = 0.035). A Kaplan-Meier curve was constructed for this exploratory outcome on day 28, and the log-rank test revealed significance (P = 0.025) (Fig 3 ). This additional outcome is the same as all-cause mortality at day 28 because all patients who deteriorated by two or more points on the seven-category ordinal scale had a score of 7 (i.e., death). A total of 131 (89.7%) participants in the placebo group were at home on day 28 compared to 137 (93.8%) in the colchicine group (odds ratio [95%CI], 0.57 [0.24-1.35] P = 0.200).
Safety outcome We actively searched for three well-known side effects of colchicine, including diarrhea, nausea/vomiting, and abdominal pain. Further, we collected self-reported adverse events
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