Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019 The GRECCO-19 Randomized Clinical Trial

Fecha de publicación: 24/06/2020 Fecha Ahead of Print: 01/06/2020

Autores de IIS La Fe

Luis Vicente Martínez Dolz

Autor

Participantes ajenos a IIS La Fe

Deftereos, SG
Giannopoulos, G
Vrachatis, DA
Siasos, GD
Giotaki, SG
Gargalianos, P
Metallidis, S
Sianos, G
Baltagiannis, S
Panagopoulos, P
Dolianitis, K
Randou, E
Syrigos, K
Kotanidou, A
Koulouris, NG
Milionis, H
Sipsas, N
Gogos, C
Tsoukalas, G
Olympios, CD
Tsagalou, E
Migdalis, I
Gerakari, S
Angelidis, C
Alexopoulos, D
Davlouros, P
Hahalis, G
Kanonidis, I
Katritsis, D
Kolettis, T
Manolis, AS
Michalis, L
Naka, KK
Pyrgakis, VN
Toutouzas, KP
Triposkiadis, F
Tsioufis, K
Vavouranakis, E
Reimers, B
Stefanini, GG
Cleman, M
Goudevenos, J
Tsiodras, S
Tousoulis, D
Iliodromitis, E
Mehran, R
Dangas, G
Stefanadis, C
GRECCO-19 Investigators

Grupos

Grupo de Investigación Clínica y Traslacional en Cardiología

Investigador Principal

Esther Roselló Lletí

Abstract

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 intention-to-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 the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution.