Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19
MD Rafael Diaz, MD Andrés Orlandini, MSc Noelia Castellana, MD Alberto Caccavo, MD Pablo Corral, MD Gonzalo Corral, MD Carolina Chacón, MD Pablo Lamelas, MD; María Fernando Botto, María Luz Díaz, MD Juan Manuel Domínguez, Andrea Pascual, Carla Rovito, MD; Agustina Galatte, MSc, MD Franco Scarafia, MD Omar Sued, MD Omar Gutierrez, PhD Sanjit S Jolly, PhD; José M Miró, MBBS John Eikelboom, MSc Mark Loeb, MD, MSc Aldo Pietro Maggioni, MD, MPH Deepak L Bhatt, MD, MPH Salim Yusuf, Lorena Lopez, Juan Muntaner, Antonela Bobato, MD Gonzalo Corral, Gustavo Benavent, Diego Espinel, Sandra M Del Valle Almagro, Eleonora E Montenegro, Adrian Núñez, Lisandro Pérez Valega, Martin Christin, Leda Guzzi, Gabriela Finelli, Lilina B Schiavi, Eduardo Ferro Queirel, Luis M Moltrasio, Horacio A Fermín, Jorge V Martínez, Omar Gutiérrez, Eleonora Cunto, Pablo A Saúl, María Del Pilar Cabrera Maciel, Javier Muntaner, Damián Lerman, Paula I Truccolo, Adrián Armano, Esther V Jalife, Romina M Bertuzzi, María Inés Jean Charles, Pablo A Fernandez, MD Alberto Caccavo, Nicolás Vittal, Lucia Lampone Tappata, Diego M Murizzi, Brenda L Fernandez, Antonio Montes De Oca, Guadalupe Diaz Vega, Felipe N Queti, Luis A Calafell, Mariano Sequeira, Ricardo León De La Fuente, Julio Núñez Burgos, Sonia Del Valle Armaraz, Patricia Flores, Mariana Bellanting, Narela Blazevich, Baltasar Finucci Curi, Romina P Cabrini, Martín E Langone, Álvaro E Figueroa, Maria T Iglesias, Maria Carolina Alvero, Cesar G Lemir, José Bonorino, María Laura Pereyra, Ezequiel Barral, Mariela Rasmussen, María F Daglio, Mariano D Estofan, Francisco M Perea, Sebastián E Duhalde, María Fernanda Motta, Ignacio Romero, Guillermo Isa Massa, Celso F García, Rubén García Durán, Elena Cornejo Pucci, Silvia Saavedra, Carolina Bozikovich, Luciano Lovesio, María J Fernandez Moutin, Cristian C G Forciniti, Hugo Colombo, Nicolas Sabas, Leonardo Pilón, Adriana P Steren
JAMA Network Open, doi:10.1001/jamanetworkopen.2021.41328
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%).
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. 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.
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