Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial

Abstract

Background Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.Methods The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0•5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97•9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FindingsTrial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53•9% women; median age 54•0 years, IQR 47•0-61•0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4•7%) of 2235 patients in the colchicine group and 131 (5•8%) of 2253 patients in the placebo group (odds ratio [OR] 0•79, 95•1% CI 0•61-1•03; p=0•081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4•6%) of 2075 patients in the colchicine group and 126 (6•0%) of 2084 patients in the placebo group (OR 0•75, 0•57-0•99; p=0•042). Serious adverse events were reported in 108 (4•9%) of 2195 patients in the colchicine group and 139 (6•3%) of 2217 patients in the placebo group (p=0•051); pneumonia occurred in 63 (2•9%) of 2195 patients in the colchicine group and 92 (4•1%) of 2217 patients in the placebo group (p=0•021). Diarrhoea was reported in 300 (13•7%) of 2195 patients in the colchicine group and 161 (7•3%) of 2217 patients in the placebo group (p<0•0001).Interpretation In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to pr...

Repurposing Colchicine in Treating Patients with COVID-19: A Systematic Review and Meta-Analysis

“…As of 31 May 2021, 147 non-duplicated articles were selected from the medical research database ( Figure 1 ). The titles and abstracts of all articles were screened, and 11 studies fulfilling the inclusion and exclusion criteria were included in the final systematic review ( Table 1 ) [ 16 , 17 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Four studies were randomized controlled trials, and the others were observational cohort studies.…”

“…For example, remdesivir was effective in patients requiring oxygen but no mechanical ventilation [ 8 ]. In our review, one study [ 17 ] enrolled non-hospitalized patients, and others were hospitalized. Meta-analysis of hospitalized patients showed a reduced risk of colchicine treatment ( Supplementary File S5 ), and further studies were required to investigate the effects of colchicine on outpatients.…”

“…During the pandemic, colchicine treatment is associated with better outcomes in previous studies [ 15 ]. However, not all studies have the same finding [ 16 , 17 ]. Therefore, we conducted this systematic review and meta-analysis to investigate the effects of colchicine in treating patients with COVID-19.…”

Low-dose aspirin for early COVID-19: does the early bird catch the worm?

“…However, an effective treatment for outpatients with mild to moderate disease has remained elusive, and no drug has been demonstrated to be effective in ambulatory setting. The COLCORONA study showed some benefit of colchicine in terms of reducing hospitalization [1], but a significant amount of gastrointestinal side effects can be induced by colchicine knowing that COVID-19 is also associated with these side effects [2].…”

Preliminary results of clinical use of colchicine in COVID-19 treatment

“…Although the study showed no significant clinical outcomes in individuals without a positive COVID-19 test, colchicine resulted in a lower rate of composite death or hospitalisation than placebo in patients with PCR-confirmed COVID-19. 14 The results of these studies are promising, as therapies to reduce hospitalisations and deaths from COVID-19 have been constantly sought since the beginning of the pandemic. Several drugs are being tested for these purposes, but a large proportion of these tend not to be widely used because they are costly drugs, unlike colchicine, an effective, safe drug that can be easily adopted as a treatment protocol for COVID-19 around the world.…”