Colchicine, an anti-inflammatory used to treat gout and rheumatic disease, reduced hospitalizations and deaths by more than 20% in COVID-19 patients in the COLCORONA trial. "Our research shows the efficacy of colchicine treatment in preventing the 'cytokine storm' phenomenon and reducing the complications associated with COVID-19," principal investigator Dr. Jean-Claude Tardif, with the Montreal Heart Institute and University of Montreal, said in a statement. "Given that colchicine is inexpensive, taken by mouth, was generally safe in this study, and does not generally need lab monitoring during use, it shows potential as the first oral drug to treat COVID-19 in the outpatient setting," Dr. Tardif and the COLCORONA trialists added in email to Reuters Health. The study was posted on medRxiv in advance of peer review. COLCORONA was a randomized, double-blind, placebo-controlled study involving 4,488 non-hospitalized patients with COVID-19 diagnosed by PCR testing or clinical criteria from Canada, the United States, Europe, South America and South Africa. The trial was designed to determine whether colchicine could reduce the risk of severe complications associated with COVID-19. All patients had at least one risk factor for progressing to more severe disease such as obesity or diabetes. They were randomly allocated to colchicine (0.5 mg twice daily for 3 days and once daily for 27 more days) or placebo for 30 days. The primary efficacy endpoint was a composite of death or hospitalization for COVID-19. For the whole study population, the primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group; the 21% reduction in death or hospitalization approached but did not reach statistical significance (odds ratio, 0.79; 95.1% confidence interval: 0.61 to 1.03; P=0.08). Among the 4,159 patients with PCR-confirmed COVID-19, colchicine was associated with a statistically significant 25% reduction in the risk of the composite of death or hospitalization compared to placebo. In this group, death or hospital admission occurred in 4.6% of those on colchicine versus 60% of those on placebo (odds ratio 0.75; 95% CI, 0.57 to 0.99; P=0.04). In the group of patients with PCR-confirmed COVID-19, early treatment colchicine lowered the likelihood of hospitalization by 25% (OR 0.75; 95% CI, 0.57 to 0.99), need for mechanical ventilation by 50% (OR 0.50; 95% CI, 0.23 to 1.07) and death by 44% (OR 0.56, 95% CI, 0.19 to 1.66). Diarrhea was reported in 13.7% of patients taking colchicine and 7.3% taking placebo. Fewer patients taking colchicine had any serious adverse event (4.9% vs 6.3%) or pneumonia (2.9% vs 4.1%). There were more reported cases of pulmonary embolism in the colchicine group (11 s 2). "Whether this represents a real phenomenon or simply the play of chance is not known," they say. The authors note that the trial was stopped when 75% of the planned patients were recruited and had completed the 30-day follow-up period. "In addition to the logistical issues faced in the current challenging context, the perceived need to disseminate the study results rapidly in view of the current state of the pandemic largely contributed to our decision," they note. They also note that the duration of follow-up was relatively short at roughly 30 days and the evolution of persistent COVID-19 symptoms and the effects of longer-term treatment with colchicine were not evaluated. "The benefit of a shorter course of colchicine therapy for less than 30 days is also not entirely known," they add. "Colchicine is a very old drug that has been used for gout for hundreds of years. Used at the doses studied in this study it is generally considered safe, and in this study, the main side effects were gastrointestinal upset and diarrhea, which are reversible with discontinuation," Dr. Tardif and colleagues told Reuters Health by email. "However, colchicine should not be used without physician supervision, and a number of factors, including severe kidney disease and a list of other drugs, can require dose adjustment or render a patient not a good candidate for the drug," they said. Commenting on the results for Reuters Health, Dr. Spyridon Deftereos, National and Kapodistrian University of Athens, Greece, noted that COLCORONA is the largest study to date in the field. "It shows a substantial reduction in the need for hospitalization and a (marginally insignificant) reduction in the need for mechanical ventilation" with colchicine. "These findings make me very optimistic. It is the only available promising treatment up to this day for non-hospitalized patients, cheap and with minimal side effects," he said by email. "Our experience with GRECCO-19 randomized controlled trial back in June 2020 was in the same direction. I would prescribe it to my patients." In the GRECCO-19 trial, 105 patients hospitalized with COVID-19 were randomly assigned to standard medical treatment alone or with colchicine (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily). The results, reported in JAMA Network Open, showed that patients treated with colchicine had statistically significantly improved time to clinical deterioration. —Megan Brooks Source
