Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19 (original) (raw)

, Nadia Bouabdallaoui, Philippe L. L’Allier, Daniel Gaudet, Binita Shah, Michael H. Pillinger, Jose Lopez-Sendon, Protasio da Luz, Lucie Verret, Sylvia Audet, Jocelyn Dupuis, View ORCID ProfileAndré Denault, Martin Pelletier, Philippe A. Tessier, Sarah Samson, Denis Fortin, Jean-Daniel Tardif, David Busseuil, Elisabeth Goulet, Chantal Lacoste, Anick Dubois, Avni Y. Joshi, David D. Waters, Priscilla Hsue, Norman E. Lepor, Frédéric Lesage, Nicolas Sainturet, Eve Roy-Clavel, Zohar Bassevitch, Andreas Orfanos, Jean C. Grégoire, Lambert Busque, Christian Lavallée, Pierre-Olivier Hétu, Jean-Sébastien Paquette, Sylvie Levesque, Mariève Cossette, View ORCID ProfileAnna Nozza, Malorie Chabot-Blanchet, View ORCID ProfileMarie-Pierre Dubé, Marie-Claude Guertin, Guy Boivin, for the COLCORONA Investigators

doi: https://doi.org/10.1101/2021.01.26.21250494

ABSTRACT

Background Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease.

Methods We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.

Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001).

Conclusion Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

Competing Interest Statement

JCT reports grants from Government of Quebec, National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health (NIH), the Montreal Heart Institute Foundation, from Bill and Melinda Gates Foundation, Amarin, Esperion, Ionis, Servier, RegenXBio; personal fees from Astra Zeneca, Sanofi, Servier; and personal fees and minor equity interest from Dalcor. In addition, JCT's institution has submitted a patent Methods of treating a coronavirus infection using Colchicine pending and a patent Early administration of low-dose colchicine after myocardial infarction pending. JCT has waived his rights in all patents related to colchicine and does not stand to benefit financially if colchicine becomes used as a treatment for COVID-19. MPD and JCT have a patent Methods for Treating or Preventing Cardiovascular Disorders and Lowering Risk of Cardiovascular Events issued to Dalcor, no royalties received, a patent Genetic Markers for Predicting Responsiveness to Therapy with HDL-Raising or HDL Mimicking Agent issued to Dalcor, no royalties received, and a patent Methods for using low dose colchicine after myocardial infarction with royalties paid to Invention assigned to the Montreal Heart Institute. NB reports personal fees from AstraZeneca; BS reports grants from NIH NHLBI; MHP reports grants from Hikma Pharmaceuticals, Horizon Therapeutics, and personal fees from Horizon Therapeutics; JLS reports grants from Bayer, Pfizer, Amgen, Boheringer Ingelheim and personal fees from Menarini; AYD reports personal fees from CAE Healthcare and Masimo, grants from Edwards; PH reports grants from NIH, Montreal Heart Institute, Gilead, and other from Merck; AO reports grants from the COVID-19 Therapeutics Accelerator; JSP reports personal fees from Universite Laval; MPD reports personal fees and other from Dalcor and personal fees from GlaxoSmithKline, other from AstraZeneca, Pfizer, Servier, Sanofi. Other authors have nothing to declare.

Clinical Trial

NCT04322682

Funding Statement

The study was funded by the Government of Quebec, the Bill and Melinda Gates Foundation, the National Institutes of Health and philanthropist Sophie Desmarais. The study medication and matching placebo were provided by Pharmascience (Montreal), which had no role in the design or conduct of the trial or the preparation or review of the manuscript. The first author (JCT) and lead statistician (MCG) prepared the first draft of the manuscript, had full access to the trial database, generated statistical analyses, made the decision to submit the manuscript for publication, and assume responsibility for the accuracy and completeness of the data and analyses and for the fidelity to the protocol.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The protocol was approved by the Montreal Heart Institute research ethics committee and all institutional review boards at all centers involved in the 6 countries that participated in the trial.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

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