Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID)

Abstract

Background Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. Objective To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. Design We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. Participants We recruited 116 hospitalized patients with severe COVID-19 in Mexico. Interventions Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. Main Measures The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. Key Results Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35–1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66–3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. Conclusions Colchicine is safe but not effective in the treatment of severe COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04367168.

Effect of colchicine on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials

“…Among the 7 RCTs, 4 were multicenter studies [ 21 , 23 , 27 , 28 ] and 3 were single-centre studies [ 24–26 ] ( Table 1 ). In addition, 2 were multinational studies [ 21 , 28 ].…”

“…In addition, 2 were multinational studies [ 21 , 28 ]. and one each was conducted in Mexico [ 27 ]. Greece [ 23 ].…”

Neutrophils in COVID-19: Not Innocent Bystanders

“…Colchicine targets the neutrophil and monocyte NLRP3 inflammasome, hence attenuating activation of IL-1β ( 112 ). However, no significant differences were seen in primary (disease progression or mortality) or secondary (time to discharge, proportion of patients discharged, time in Intensive Care unit (ICU) or duration of hospitalisation) outcomes in two separated clinical trials comparing patients who were given colchicine to placebo/usual care treated patients ( 113 , 114 ). Anakinra (commercially known as Kineret) is an FDA approved human IL-1RA (inflammasome-regulated immune response inhibitor of IL-1) which may reduce hyperinflammation and organ damage ( Table 1 ) ( 112 ).…”

Clinical update on COVID-19 for the emergency and critical care clinician: Medical management

“…Several RCTs demonstrated decreased duration of supplemental oxygen and lower rates of pneumonia development with use of colchicine in COVID-19. However, colchicine was associated with increased risk of gastrointestinal side effects and rates of pulmonary embolism and no significant differences in mortality [ 118 , 119 , 122 ]. Despite enthusiasm from a small initial Italian study showing mortality benefit in patients receiving colchicine compared to standard care, the majority of evidence to-date, including several larger trials and meta-analyses, have found no significant mortality benefit for colchicine [ 118 , [120] , [121] , [122] , [123] , [124] , [125] , [126] ].…”