Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019
MD Spyridon G Deftereos, PhD Georgios Giannopoulos, MD, PhD Dimitrios A Vrachatis, PhD Gerasimos D Siasos, PhD Sotiria G Giotaki, MD Panagiotis Gargalianos, MD, PhD Simeon Metallidis, PhD George Sianos, PhD Stefanos Baltagiannis, MD, MSc Periklis Panagopoulos, PhD Konstantinos Dolianitis, MD, MSc Efthalia Randou, MD Konstantinos Syrigos, MD, PhD Anastasia Kotanidou, PhD Nikolaos G Koulouris, PhD Haralampos Milionis, PhD Nikolaos Sipsas, PhD Charalampos Gogos, PhD George Tsoukalas, PhD Christoforos D Olympios, PhD Eleftheria Tsagalou, MD, PhD; Ilias Ilias Migdalis, PhD Styliani Gerakari, MD Christos Angelidis, MD Dimitrios Alexopoulos, PhD Pericles Davlouros, PhD George Hahalis, MD, PhD; Ioannis Ioannis Kanonidis, PhD Demosthenes Katritsis, PhD Theofilos Kolettis, PhD Antonios S Manolis, PhD Lampros Michalis, MD, PhD Katerina K Naka, PhD Vlasios N Pyrgakis, Konstantinos P Toutouzas, PhD Filippos Triposkiadis, PhD Konstantinos Tsioufis, PhD Emmanouil Vavouranakis, Luis Martinèz-Dolz, MD, PhD Bernhard Reimers, MD Giulio G Stefanini, PhD; Michael Cleman, PhD; John Goudevenos, PhD Sotirios Tsiodras, MD, PhD Dimitrios Tousoulis, PhD Efstathios Iliodromitis, MD, PhD Roxana Mehran, PhD George Dangas, PhD Christodoulos Stefanadis
JAMA Network Open, doi:10.1001/jamanetworkopen.2020.13136
IMPORTANCE Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. OBJECTIVE To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). DESIGN, SETTING, AND PARTICIPANTS In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. INTERVENTION Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks.
MAIN OUTCOMES AND MEASURES Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intentionto-treat basis. RESULTS A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in (continued) Key Points Question Is the receipt of colchicine among patients hospitalized with symptomatic coronavirus disease 2019 associated with clinical benefit? Findings In this randomized clinical trial of 105 patients, the rate of the primary clinical end point (clinical deterioration) was higher in the control group than in the colchicine group, and the time to clinical deterioration was shorter in the control group than in the colchicine arm. No difference was observed in the primary biochemical end point (highsensitivity troponin concentration), but patients in the colchicine group had a smaller increase in dimerized plasma fragment D compared with patients in the control group. Meaning The hypothesis-generating findings of this study suggest a role for colchicine in the treatment of patients with..
ARTICLE INFORMATION Accepted for Publication: May 29, 2020. Published: June 24, 2020. doi:10.1001/jamanetworkopen.2020.13136 Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Deftereos SG et al. JAMA Network Open.
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