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

Abdiel Absalón-Aguilar,Jiram Torres-Ruiz,Martha Ramírez-Alemón,Guillermo Juárez-Vega,Diana Gómez-Martín,Manlio F Márquez,Alfredo Pérez-Fragoso,Alfredo Ponce-De-León,Nancy R Mejía-Domínguez,Pamela Ramírez-Rangel,Marina Rull-Gabayet,Eduardo Martín-Nares,Carlos Núñez-Álvarez,José Sifuentes-Osornio,Sharon Montesinos-Ramírez,Juan Carlos Plata-Corona,David Kershenobich-Stalnikowitz,Fernanda González-Lara

doi:10.1007/s11606-021-07203-8

Abstract

BackgroundColchicine 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.ObjectiveTo address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19.DesignWe conducted a triple-blind parallel non-stratified placebo-controlled clinical trial.ParticipantsWe recruited 116 hospitalized patients with severe COVID-19 in Mexico.InterventionsPatients 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 MeasuresThe 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 ResultsFifty-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.ConclusionsColchicine is safe but not effective in the treatment of severe COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04367168.

Highlights

The coronavirus disease 2019 (COVID-19) has overwhelmed most health systems around the world since its emergence in December 2019
Neutrophils and macrophages are the main cells involved in the pathogenesis of respiratory viral infections
Neutrophilia at COVID-19 diagnosis is a risk factor for critical disease[2] and neutrophil extracellular neutrophil traps (NETs) are a key pathogenic factor in COVID-19.3 NETs contribute to the cytokine storm by promoting IL-1β secretion in macrophages via the inflammasome activation, which induces IL-6 production[4] and favors a hypercoagulability state.[5]

Summary

Introduction

The coronavirus disease 2019 (COVID-19) has overwhelmed most health systems around the world since its emergence in December 2019. Neutrophilia at COVID-19 diagnosis is a risk factor for critical disease[2] and neutrophil extracellular neutrophil traps (NETs) are a key pathogenic factor in COVID-19.3 NETs contribute to the cytokine storm by promoting IL-1β secretion in macrophages via the inflammasome activation, which induces IL-6 production[4] and favors a hypercoagulability state.[5]. There are only few effective treatments to avoid the potentially devastating effects of this virus.[6] Disease severity and lack of treatment options for COVID-19 have led to off-label prescription of a myriad of drugs based on low-evidence studies. 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

Methods

Results

Conclusion