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

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.

Trial registration: ClinicalTrials.gov Identifier: NCT04326790.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Vrachatis reported receiving a scholarship from Hellenic Society of Cardiology. Dr Michalis reported receiving grants and nonfinancial support from ELPEN Pharmaceuticals outside the submitted work. Dr Naka reported receiving grants and nonfinancial support from ELPEN Pharmaceuticals outside the submitted work. Dr Stefanini reported receiving a research grant to his institution and speaker fees from Boston Scientific and speaker fees from B. Braun Medical, Biosensors, and GADA outside the submitted work. Dr Mehran reported receiving grants and personal fees from Abbott Laboratories; grants from Applied Therapeutics, Bayer, Beth Israel Deaconess, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; receiving grants from and serving on the advisory board of Bristol-Myers Squibb; receiving grants from and having a spouse who is a consultant for Abiomed; having a spouse who is a consultant for The Medicines Company; serving as a consultant for Boston Scientific, Janssen Scientific Affairs, Medscape/WebMD, Roivant Services, Sanofi, Siemens Medical Solutions, and Spectranetics/Philips/Volcano; receiving nonfinancial support from Idorsia Pharmaceuticals and Regeneron Pharmaceuticals; receiving advisory and speaking fees from Medtelligence (Janssen Scientific Affairs); serving on the data safety monitoring board for Watermark Research Partners; owning equity in Claret Medical and Elixir Medical; and serving as associate editor for ACC and JAMA Cardiology outside the submitted work. Dr Dangas reported receiving grants and personal fees from AstraZeneca, Janssen Pharmaceuticals, Sanofi, and Abbott Laboratories and receiving grants from Bayer, Daiichi-Sankyo, Bristol-Myers Squibb, and Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Flow Diagram

Figure 2.. Kaplan-Meier Curves for Survival From the Primary Clinical End Point