Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019

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 (high-sensitivity 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 coronavirus disease 2019.

[1]  G. Dangas,et al.  Colchicine as a potent anti-inflammatory treatment in COVID-19: can we teach an old dog new tricks? , 2020, European heart journal. Cardiovascular pharmacotherapy.

[2]  Yutao Guo,et al.  COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up , 2020, Journal of the American College of Cardiology.

[3]  C. Schmidt,et al.  Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States During COVID-19 Pandemic , 2020, Journal of the American College of Cardiology.

[4]  M. Lazanas,et al.  The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design , 2020, Hellenic Journal of Cardiology.

[5]  Binita Shah,et al.  Effects of Acute Colchicine Administration Prior to Percutaneous Coronary Intervention , 2020, Circulation. Cardiovascular interventions.

[6]  Yi Feng,et al.  The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2 , 2020, Cardiovascular research.

[7]  W. Gong,et al.  Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. , 2020, JAMA cardiology.

[8]  Yuan Wei,et al.  A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19 , 2020, The New England journal of medicine.

[9]  Xin Zhou,et al.  Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China , 2020, The Journal of Emergency Medicine.

[10]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[11]  A. Walls,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[12]  Ivan Griffin,et al.  COVID-19: combining antiviral and anti-inflammatory treatments , 2020, The Lancet Infectious Diseases.

[13]  R. Diaz,et al.  Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. , 2019, The New England journal of medicine.

[14]  N. Gupta,et al.  The stimulation of thrombosis by hypoxia. , 2019, Thrombosis research.

[15]  C. Shi,et al.  SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes , 2019, Cell Death Discovery.

[16]  K. Yuen,et al.  Severe acute respiratory syndrome Coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of ASC , 2019, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  Takeshi Ichinohe,et al.  Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome , 2019, Front. Microbiol..

[18]  Zhilong Jiang,et al.  Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury , 2018, Molecular medicine reports.

[19]  K. Gotman of Medicine , 2003 .

[20]  S. Perlman,et al.  Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis , 2018, mBio.

[21]  M. Kaksonen,et al.  Mechanisms of clathrin-mediated endocytosis , 2018, Nature Reviews Molecular Cell Biology.

[22]  Charalampos Kossyvakis,et al.  Colchicine Pharmacokinetics and Mechanism of Action. , 2018, Current pharmaceutical design.

[23]  V. Kraus,et al.  Colchicine--Update on mechanisms of action and therapeutic uses. , 2015, Seminars in arthritis and rheumatism.

[24]  G. Filippatos,et al.  Anti‐Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study , 2015, Circulation.

[25]  P. Ward,et al.  Critical Role for the NLRP3 Inflammasome during Acute Lung Injury , 2014, The Journal of Immunology.

[26]  J. Dagvadorj,et al.  The NLRP3 inflammasome is required for the development of hypoxemia in LPS/mechanical ventilation acute lung injury. , 2013, American journal of respiratory cell and molecular biology.

[27]  M. Cleman,et al.  Colchicine and the heart: pushing the envelope. , 2013, Journal of the American College of Cardiology.

[28]  S. Akira,et al.  Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome , 2013, Nature Immunology.

[29]  S. Ryter,et al.  Inflammasome-regulated cytokines are critical mediators of acute lung injury. , 2012, American journal of respiratory and critical care medicine.

[30]  R. Coutinho-Silva,et al.  Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor‐expressing cells: implications for its therapeutic action , 2011, British journal of pharmacology.

[31]  G. Antes,et al.  CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials , 2011 .

[32]  D. Moher,et al.  CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials , 2010, BMC medicine.

[33]  A. Ozkan,et al.  Is Familial Mediterranean Fever a thrombotic disease or not? , 2008, European Journal of Pediatrics.

[34]  N. Black CONSORT , 1996, The Lancet.