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Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19A Randomized Clinical Trial

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Key Points

Question  Does colchicine prevent intubation and mortality in hospitalized patients with COVID-19 pneumonia?

Findings  In this randomized clinical trial of 1279 patients hospitalized with COVID-19, patients allocated to receive colchicine plus usual care or to usual care alone demonstrated no significant difference in the coprimary outcome of mechanical ventilation or 28-day mortality.

Meaning  This randomized clinical trial found that colchicine did not significantly reduce the need for mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia.

Abstract

Importance  Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality.

Objective  To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia.

Design, Setting, and Participants  The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription–polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021.

Interventions  Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first.

Main Outcomes and Measures  The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days.

Results  A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%).

Conclusions and Relevance  This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia.

Trial Registration  ClinicalTrials.gov Identifier: NCT04328480

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: November 2, 2021.

Published: December 29, 2021. doi:10.1001/jamanetworkopen.2021.41328

Correction: This article was corrected on February 18, 2022, to fix omitted information on the data and safety monitoring board.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Diaz R et al. JAMA Network Open.

Corresponding Author: Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115 (dlbhattmd@post.harvard.edu).

Author Contributions: Dr Diaz and Ms Castellana had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Diaz, Orlandini, Castellana, Caccavo, P. Corral, G. Corral, Chacón, Lamelas, Botto, Díaz, Domínguez, Pascual, Galatte, Jolly, Miró, Eikelboom, Maggioni, Bhatt, Yusuf.

Acquisition, analysis, or interpretation of data: Diaz, Orlandini, Castellana, Caccavo, P. Corral, G. Corral, Chacón, Botto, Domínguez, Rovito, Scarafia, Sued, Gutierrez, Jolly, Miró, Eikelboom, Loeb, Maggioni, Bhatt, Yusuf.

Drafting of the manuscript: Diaz, Orlandini, Castellana, Caccavo, P. Corral, G. Corral, Lamelas, Díaz, Domínguez, Pascual, Rovito, Galatte, Scarafia.

Critical revision of the manuscript for important intellectual content: Diaz, Orlandini, Castellana, Caccavo, P. Corral, G. Corral, Chacón, Lamelas, Botto, Sued, Gutierrez, Jolly, Miró, Eikelboom, Loeb, Maggioni, Bhatt, Yusuf.

Statistical analysis: Orlandini, Castellana, Domínguez, Scarafia, Eikelboom, Yusuf.

Obtained funding: Orlandini, Yusuf.

Administrative, technical, or material support: Orlandini, Castellana, Caccavo, P. Corral, Chacón, Botto, Díaz, Pascual, Rovito, Galatte, Sued, Gutierrez, Jolly, Loeb, Bhatt.

Supervision: Diaz, Orlandini, Castellana, Caccavo, P. Corral, Lamelas, Botto, Díaz, Galatte, Gutierrez, Jolly, Miró, Bhatt.

Conflict of Interest Disclosures: Dr Orlandini reported receiving grants from Population Health Research Institution during the conduct of the study. Dr Lamelas reported receiving personal fees from Boston Scientific, Medtronic, Edwards, and Meril outside the submitted work. Dr Miró reported receiving grants from Angelini, Contrafect, Gilead Sciences, MSD, Novartis, Pfizer, and ViiV Healthcare and personal fees from Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, and Pfizer outside the submitted work. Dr Eikelboom reported receiving grants and personal fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi-Aventis and personal fees from Daiichi-Sankyo, Eli-Lilly, and Servier during the conduct of the study. Dr Loeb reported receiving personal fees from Seqirus, Sanofi, Medicago, Pfizer, and Merck outside the submitted work. Dr Maggioni reported receiving personal fees from Bayer, Novartis, Fresenius, and AstraZeneca outside the submitted work. Dr Bhatt reported receiving grants from Amarin, AstraZeneca, Forest Laboratories, Bristol Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company, Roche, Pfizer, Ischemix, Cardax, Amgen, Lilly, Chiesi, Ironwood, PhaseBio, Idorsia, Synaptic, Abbott, Regeneron, Novo Nordisk, Fractyl, Cereno Scientific, Afimmune, Ferring Pharmaceuticals, Contego Medical, CellProthera, Lexicon, MyoKardia, Owkin, HLS Therapeutics, Janssen, 89Bio, Garmin, PLxPharma, and Novartis; personal fees from Duke Clinical Research Institute, Mayo Clinic, Population Health Research Institute, American College of Cardiology, Belvoir Publications, Slack Publications, WebMD, Elsevier, Society of Cardiovascular Patient Care, HMP Global, Harvard Clinical Research Institute (now Baim Institute for Clinical Research), Journal of the American College of Cardiology, American Heart Association, Cleveland Clinic, Mount Sinai School of Medicine, TobeSoft, Boehringer Ingelheim, Bayer, Medtelligence/ReachMD, CSL Behring, MJH Life Sciences, Level Ex, K2P, and Canadian Medical and Surgical Knowledge Translation Research Group; serving as a site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, and Svelte; performing unfunded research for FlowCo, Merck, and Takeda; serving on an advisory board for Medscape Cardiology and Regado Biosciences; serving as a deputy editor for Clinical Cardiology and on the publications committee for VA CART Research and Publications Committee; and serving on the board of directors for Boston VA Research Institute No other disclosures were reported.

Funding/Support: The Population Health Research Institute contributed fees to the investigators. Fundacion ECLA funded all other aspects of the trial.

Role of the Funder/Sponsor: Fundacion ECLA was responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The ECLA PHRI COLCOVID Trial Investigators: The ECLA PHRI COLCOVID Trial Investigators are listed in Supplement 3.

Data Sharing Statement: See Supplement 4.

Additional Contributions: Roles of committee and other members of the ECLA PHRI COLCOVID Trial Group include the following: Executive Committee: Rafael Diaz, MD (chair); Andrés Orlandini, MD (cochair); Omar Sued, MD; Pablo Corral, MD; Gonzalo Corral, MD; Carolina Chacón, MD; María Luz Díaz, MD; Alberto Caccavo, MD; Fernando Botto, MD; Pablo Lamelas, MD; Juan Manuel Dominguez, MD; José M Miro, PhD; and Sanjit S. Jolly, MD, MSc; Event Adjudication Committee: Pablo Corral, MD (cochair); Gonzalo Corral, MD, (cochair); María Luz Díaz, MD; Juan Manuel Dominguez, MD; and Agustina Galatte, MD; Data and Safety Monitoring Board (DSMB): Salim Yusuf, DPhil (chair); Aldo Pietro Maggioni, PhD; Mark Loeb, MD, MSc; Michael Szarek, PhD; and Deepak L. Bhatt, MD, MPH; Statistician Reporting to DSMB: Noelia Castellana, MSc; Study Statisticians and Programmers: Noelia Castellana, MSc (chair); Franco Scarafia, MSc; and Pablo Lamelas, MD; Trial Central Coordinating Office: Andrea Pascual, Ing; Carla Rovito, MRA; Mauricio Salvador, JD; Maximiliano Guerrero, CPA; Martin Arrieta, Adm; and Miguel A. Cabezón, BIOCH.

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