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All Studies   Meta Analysis    Recent:   

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

Deftereos et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.13136, GRECCO-19, NCT04326790
Jun 2020  
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Mortality 77% Improvement Relative Risk Ventilation 82% Clinical deterioration 87% Colchicine  GRECCO-19  LATE TREATMENT  RCT Is late treatment with colchicine beneficial for COVID-19? RCT 105 patients in Greece (April - April 2020) Lower progression with colchicine (p=0.046) c19early.org Deftereos et al., JAMA Network Open, Jun 2020 Favorscolchicine Favorscontrol 0 0.5 1 1.5 2+
Colchicine for COVID-19
5th treatment shown to reduce risk in September 2020
 
*, now with p = 0.00000031 from 56 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 98 treatments. c19early.org
RCT with 55 patients treated with colchicine and 50 control patients, showing lower mortality and ventilation with treatment.
risk of death, 77.3% lower, RR 0.23, p = 0.19, treatment 1 of 55 (1.8%), control 4 of 50 (8.0%), NNT 16.
risk of mechanical ventilation, 81.8% lower, RR 0.18, p = 0.10, treatment 1 of 55 (1.8%), control 5 of 50 (10.0%), NNT 12.
risk of clinical deterioration, 87.4% lower, RR 0.13, p = 0.046, treatment 1 of 55 (1.8%), control 7 of 50 (14.0%), NNT 8.2, odds ratio converted to relative risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Deftereos et al., 24 Jun 2020, Randomized Controlled Trial, Greece, peer-reviewed, baseline oxygen required 62.9%, 49 authors, study period 3 April, 2020 - 27 April, 2020, dosage 2mg day 1, 1mg days 2-21, trial NCT04326790 (history) (GRECCO-19).
This PaperColchicineAll
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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'affiliation': [ { 'name': 'Department of Internal Medicine, General Hospital of Kozani, ' 'Kozani, Greece'}]}, { 'given': 'Konstantinos', 'family': 'Syrigos', 'sequence': 'additional', 'affiliation': [ { 'name': 'Third Department of Internal Medicine, General Hospital Sotiria, ' 'National and Kapodistrian University of Athens, Athens, ' 'Greece'}]}, { 'given': 'Anastasia', 'family': 'Kotanidou', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Intensive Care Unit, General Hospital Evangelismos, ' 'National and Kapodistrian University of Athens, Athens, ' 'Greece'}]}, { 'given': 'Nikolaos G.', 'family': 'Koulouris', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Department of Pneumonology, General Hospital Sotiria, ' 'National and Kapodistrian University of Athens, Athens, ' 'Greece'}]}, { 'given': 'Haralampos', 'family': 'Milionis', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Department of Internal Medicine, Ioannina University ' 'Hospital, 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'additional', 'affiliation': [ { 'name': 'Department of Cardiology, Ioannina University Hospital, ' 'University of Ioannina, Ioannina, Greece'}]}, { 'given': 'Katerina K.', 'family': 'Naka', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Cardiology, Ioannina University Hospital, ' 'University of Ioannina, Ioannina, Greece'}]}, { 'given': 'Vlasios N.', 'family': 'Pyrgakis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Cardiology, G. Gennimatas General Hospital of ' 'Athens, Athens, Greece'}]}, { 'given': 'Konstantinos P.', 'family': 'Toutouzas', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Department of Cardiology, Hippokration Hospital, National ' 'and Kapodistrian University of Athens, Athens, Greece'}]}, { 'given': 'Filippos', 'family': 'Triposkiadis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Cardiology, University General Hospital of ' 'Larissa, Larissa, Greece'}]}, { 'given': 'Konstantinos', 'family': 'Tsioufis', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Department of Cardiology, Hippokration Hospital, National ' 'and Kapodistrian University of Athens, Athens, Greece'}]}, { 'given': 'Emmanouil', 'family': 'Vavouranakis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Third Department of Cardiology, General Hospital Sotiria, ' 'National and Kapodistrian University of Athens, Athens, ' 'Greece'}]}, { 'given': 'Luis', 'family': 'Martinèz-Dolz', 'sequence': 'additional', 'affiliation': [{'name': 'Hospital Universitario y Politécnico La Fe, Valencia, Spain'}]}, { 'given': 'Bernhard', 'family': 'Reimers', 'sequence': 'additional', 'affiliation': [ { 'name': 'Cardio Center, Humanitas Clinical and Research Hospital IRCCS, ' 'Rozzano-Milan, Italy'}]}, { 'given': 'Giulio G.', 'family': 'Stefanini', 'sequence': 'additional', 'affiliation': [ { 'name': 'Cardio Center, Humanitas Clinical and Research Hospital IRCCS, ' 'Rozzano-Milan, Italy'}]}, { 'given': 'Michael', 'family': 'Cleman', 'sequence': 'additional', 'affiliation': [ { 'name': 'Section of Cardiovascular Medicine, Yale University School of ' 'Medicine, New Haven, Connecticut'}]}, { 'given': 'John', 'family': 'Goudevenos', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Cardiology, Ioannina University Hospital, ' 'University of Ioannina, Ioannina, Greece'}]}, { 'given': 'Sotirios', 'family': 'Tsiodras', 'sequence': 'additional', 'affiliation': [ { 'name': 'Fourth Department of Internal Medicine, Attikon Hospital, ' 'National and Kapodistrian University of Athens, Athens, ' 'Greece'}]}, { 'given': 'Dimitrios', 'family': 'Tousoulis', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Department of Cardiology, Hippokration Hospital, National ' 'and Kapodistrian University of Athens, Athens, Greece'}]}, { 'given': 'Efstathios', 'family': 'Iliodromitis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Second Department of Cardiology, Attikon Hospital, National and ' 'Kapodistrian University of Athens, Athens, Greece'}]}, { 'given': 'Roxana', 'family': 'Mehran', 'sequence': 'additional', 'affiliation': [{'name': 'Icahn School of Medicine at Mount Sinai, New York, New York'}]}, { 'given': 'George', 'family': 'Dangas', 'sequence': 'additional', 'affiliation': [{'name': 'Icahn School of Medicine at Mount Sinai, New York, New York'}]}, { 'given': 'Christodoulos', 'family': 'Stefanadis', 'sequence': 'additional', 'affiliation': [ { 'name': 'First Department of Cardiology, Hippokration Hospital, National ' 'and Kapodistrian University of Athens, Athens, Greece'}, {'name': 'Athens Medical Center, Athens, Greece'}]}, { 'name': 'on behalf of the GRECCO-19 investigators', 'sequence': 'additional', 'affiliation': []}], 'member': '10', 'published-online': {'date-parts': [[2020, 6, 24]]}, 'reference': [ { 'key': 'zoi200495r1', 'doi-asserted-by': 'crossref', 'DOI': '10.1001/jamainternmed.2020.0994', 'article-title': 'Risk factors associated with acute respiratory distress syndrome and ' 'death in patients with coronavirus disease 2019 pneumonia in Wuhan, ' 'China.', 'author': 'Wu', 'year': '2020', 'journal-title': 'JAMA Intern Med'}, { 'issue': '20', 'key': 'zoi200495r2', 'doi-asserted-by': 'publisher', 'first-page': '1817', 'DOI': '10.1016/j.jacc.2013.08.726', 'article-title': 'Colchicine and the heart: pushing the envelope.', 'volume': '62', 'author': 'Deftereos', 'year': '2013', 'journal-title': 'J Am Coll Cardiol'}, { 'issue': '3', 'key': 'zoi200495r3', 'doi-asserted-by': 'publisher', 'first-page': '341', 'DOI': '10.1016/j.semarthrit.2015.06.013', 'article-title': 'Colchicine—update on mechanisms of action and therapeutic uses.', 'volume': '45', 'author': 'Leung', 'year': '2015', 'journal-title': 'Semin Arthritis Rheum'}, { 'key': 'zoi200495r5', 'doi-asserted-by': 'crossref', 'DOI': '10.1093/ehjcvp/pvaa033', 'article-title': 'Colchicine as a potent anti-inflammatory treatment in COVID-19: can we ' 'teach an old dog new tricks?', 'author': 'Deftereos', 'year': '2020', 'journal-title': 'Eur Hear J Cardiovasc Pharmacother'}, { 'key': 'zoi200495r6', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.hjc.2020.03.002', 'article-title': 'The Greek Study in the Effects of Colchicine in COVID-19 Complications ' 'Prevention (GRECCO-19 study): rationale and study design.', 'author': 'Deftereos', 'year': '2020', 'journal-title': 'Hellenic J Cardiol'}, { 'key': 'zoi200495r8', 'doi-asserted-by': 'publisher', 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'article-title': 'Colchicine pharmacokinetics and mechanism of action.', 'volume': '24', 'author': 'Angelidis', 'year': '2018', 'journal-title': 'Curr Pharm Des'}, { 'key': 'zoi200495r13', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.jacc.2020.04.031', 'article-title': 'COVID-19 and thrombotic or thromboembolic disease: implications for ' 'prevention, antithrombotic therapy, and follow-up.', 'author': 'Bikdeli', 'year': '2020', 'journal-title': 'J Am Coll Cardiol'}, { 'issue': '10229', 'key': 'zoi200495r14', 'doi-asserted-by': 'publisher', 'first-page': '1054', 'DOI': '10.1016/S0140-6736(20)30566-3', 'article-title': 'Clinical course and risk factors for mortality of adult inpatients with ' 'COVID-19 in Wuhan, China: a retrospective cohort study.', 'volume': '395', 'author': 'Zhou', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'zoi200495r15', 'doi-asserted-by': 'publisher', 'first-page': '77', 'DOI': '10.1016/j.thromres.2019.07.013', 'article-title': 'The stimulation of thrombosis by hypoxia.', 'volume': '181', 'author': 'Gupta', 'year': '2019', 'journal-title': 'Thromb Res'}, { 'issue': '26', 'key': 'zoi200495r16', 'doi-asserted-by': 'publisher', 'first-page': '2497', 'DOI': '10.1056/NEJMoa1912388', 'article-title': 'Efficacy and safety of low-dose colchicine after myocardial infarction.', 'volume': '381', 'author': 'Tardif', 'year': '2019', 'journal-title': 'N Engl J Med'}, { 'issue': '15', 'key': 'zoi200495r17', 'doi-asserted-by': 'publisher', 'first-page': '1395', 'DOI': '10.1161/CIRCULATIONAHA.115.017611', 'article-title': 'Anti-inflammatory treatment with colchicine in acute myocardial ' 'infarction: a pilot study.', 'volume': '132', 'author': 'Deftereos', 'year': '2015', 'journal-title': 'Circulation'}, { 'key': 'zoi200495r18', 'doi-asserted-by': 'crossref', 'DOI': '10.1001/jamacardio.2020.0950', 'article-title': 'Association of cardiac injury with mortality in hospitalized patients ' 'with COVID-19 in Wuhan, China.', 'author': 'Shi', 'year': '2020', 'journal-title': 'JAMA Cardiol'}, { 'issue': '4', 'key': 'zoi200495r19', 'doi-asserted-by': 'crossref', 'DOI': '10.1161/CIRCINTERVENTIONS.119.008717', 'article-title': 'Effects of acute colchicine administration prior to percutaneous ' 'coronary intervention: COLCHICINE-PCI randomized trial.', 'volume': '13', 'author': 'Shah', 'year': '2020', 'journal-title': 'Circ Cardiovasc Interv'}, { 'issue': 'April', 'key': 'zoi200495r20', 'article-title': 'Reduction in ST-segment elevation cardiac catheterization laboratory ' 'activations in the United States during COVID-19 pandemic.', 'author': 'Garcia', 'year': '2020', 'journal-title': 'J Am Coll Cardiol'}, { 'issue': '6', 'key': 'zoi200495r21', 'doi-asserted-by': 'publisher', 'first-page': '1097', 'DOI': '10.1093/cvr/cvaa078', 'article-title': 'The ACE2 expression in human heart indicates new potential mechanism of ' 'heart injury among patients infected with SARS-CoV-2.', 'volume': '116', 'author': 'Chen', 'year': '2020', 'journal-title': 'Cardiovasc Res'}, { 'issue': '2', 'key': 'zoi200495r22', 'doi-asserted-by': 'publisher', 'first-page': '281', 'DOI': '10.1016/j.cell.2020.02.058', 'article-title': 'Structure, function, and antigenicity of the SARS-CoV-2 spike ' 'glycoprotein.', 'volume': '181', 'author': 'Walls', 'year': '2020', 'journal-title': 'Cell'}, { 'issue': '3', 'key': 'zoi200495r23', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/mBio.02325-17', 'article-title': 'Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, ' 'and 8a in replication and pathogenesis.', 'volume': '9', 'author': 'Castaño-Rodriguez', 'year': '2018', 'journal-title': 'mBio'}, { 'issue': '5', 'key': 'zoi200495r24', 'doi-asserted-by': 'publisher', 'first-page': '313', 'DOI': '10.1038/nrm.2017.132', 'article-title': 'Mechanisms of clathrin-mediated endocytosis.', 'volume': '19', 'author': 'Kaksonen', 'year': '2018', 'journal-title': 'Nat Rev Mol Cell Biol'}, { 'issue': '4', 'key': 'zoi200495r25', 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'first-page': '270', 'DOI': '10.1165/rcmb.2013-0087OC', 'article-title': 'The NLRP3 inflammasome is required for the development of hypoxemia in ' 'LPS/mechanical ventilation acute lung injury.', 'volume': '50', 'author': 'Jones', 'year': '2014', 'journal-title': 'Am J Respir Cell Mol Biol'}, { 'issue': '11', 'key': 'zoi200495r32', 'doi-asserted-by': 'publisher', 'first-page': '1225', 'DOI': '10.1164/rccm.201201-0003OC', 'article-title': 'Inflammasome-regulated cytokines are critical mediators of acute lung ' 'injury.', 'volume': '185', 'author': 'Dolinay', 'year': '2012', 'journal-title': 'Am J Respir Crit Care Med'}, { 'issue': '5', 'key': 'zoi200495r33', 'doi-asserted-by': 'publisher', 'first-page': '912', 'DOI': '10.1111/j.1476-5381.2011.01254.x', 'article-title': 'Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 ' 'receptor-expressing cells: implications for its therapeutic action.', 'volume': '163', 'author': 'Marques-da-Silva', 'year': '2011', 'journal-title': 'Br J Pharmacol'}, { 'issue': '5', 'key': 'zoi200495r34', 'doi-asserted-by': 'publisher', 'first-page': '454', 'DOI': '10.1038/ni.2550', 'article-title': 'Microtubule-driven spatial arrangement of mitochondria promotes ' 'activation of the NLRP3 inflammasome.', 'volume': '14', 'author': 'Misawa', 'year': '2013', 'journal-title': 'Nat Immunol'}, { 'key': 'zoi200495r4', 'unstructured': 'US National Library of Medicine. Colchicine Coronavirus SARS-CoV2 Trial ' '(COLCORONA) (COVID-19). Accessed June 4, 2020. ' 'https://clinicaltrials.gov/ct2/show/NCT04322682'}, { 'key': 'zoi200495r7', 'unstructured': 'National Public Health Organization. Coronavirus disease (COVID-19). ' 'Accessed June 3, 2020. https://eody.gov.gr/en'}, { 'key': 'zoi200495r9', 'unstructured': 'World Health Organization. R&D blueprint and COVID-19. Accessed March ' '25, 2020. ' 'https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/'}], 'container-title': 'JAMA Network Open', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2767593/deftereos_2020_oi_200495.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 10, 30]], 'date-time': '2022-10-30T07:02:48Z', 'timestamp': 1667113368000}, 'score': 1, 'resource': {'primary': {'URL': 'https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593'}}, 'subtitle': ['The GRECCO-19 Randomized Clinical Trial'], 'short-title': [], 'issued': {'date-parts': [[2020, 6, 24]]}, 'references-count': 34, 'journal-issue': {'issue': '6', 'published-print': {'date-parts': [[2020, 6, 1]]}}, 'URL': 'http://dx.doi.org/10.1001/jamanetworkopen.2020.13136', 'relation': {}, 'ISSN': ['2574-3805'], 'subject': ['General Medicine'], 'container-title-short': 'JAMA Netw Open', 'published': {'date-parts': [[2020, 6, 24]]}}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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