Spyridon G Deftereos1, Georgios Giannopoulos2, Dimitrios A Vrachatis3, Gerasimos D Siasos4, Sotiria G Giotaki1, Panagiotis Gargalianos5, Simeon Metallidis6, George Sianos7, Stefanos Baltagiannis8, Periklis Panagopoulos9, Konstantinos Dolianitis10, Efthalia Randou11, Konstantinos Syrigos12, Anastasia Kotanidou13, Nikolaos G Koulouris14, Haralampos Milionis15, Nikolaos Sipsas16, Charalampos Gogos17, George Tsoukalas18, Christoforos D Olympios19, Eleftheria Tsagalou20, Ilias Migdalis21, Styliani Gerakari22, Christos Angelidis1, Dimitrios Alexopoulos1, Pericles Davlouros23, George Hahalis23, Ioannis Kanonidis24, Demosthenes Katritsis25, Theofilos Kolettis26, Antonios S Manolis4, Lampros Michalis26, Katerina K Naka26, Vlasios N Pyrgakis2, Konstantinos P Toutouzas4, Filippos Triposkiadis27, Konstantinos Tsioufis4, Emmanouil Vavouranakis28, Luis Martinèz-Dolz29, Bernhard Reimers3, Giulio G Stefanini3, Michael Cleman30, John Goudevenos26, Sotirios Tsiodras31, Dimitrios Tousoulis4, Efstathios Iliodromitis1, Roxana Mehran32, George Dangas32, Christodoulos Stefanadis4,5. 1. Second Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece. 2. Department of Cardiology, G. Gennimatas General Hospital of Athens, Athens, Greece. 3. Cardio Center, Humanitas Clinical and Research Hospital IRCCS, Rozzano-Milan, Italy. 4. First Department of Cardiology, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece. 5. Athens Medical Center, Athens, Greece. 6. First Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 7. First Department of Cardiology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 8. Department of Internal Medicine, General Hospital of Kastoria, Kastoria, Greece. 9. Second Department of Internal Medicine, General Hospital of Alexandroupoli, Democritus University of Thrace, Alexandroupoli, Greece. 10. Department of Internal Medicine, Mpodosakio General Hospital of Ptolemaida, Ptolemaida, Greece. 11. Department of Internal Medicine, General Hospital of Kozani, Kozani, Greece. 12. Third Department of Internal Medicine, General Hospital Sotiria, National and Kapodistrian University of Athens, Athens, Greece. 13. First Intensive Care Unit, General Hospital Evangelismos, National and Kapodistrian University of Athens, Athens, Greece. 14. First Department of Pneumonology, General Hospital Sotiria, National and Kapodistrian University of Athens, Athens, Greece. 15. First Department of Internal Medicine, Ioannina University Hospital, University of Ioannina, Ioannina, Greece. 16. Infectious Diseases Unit, Laiko General Hospital, Athens, Greece. 17. Internal Medicine Department, University Hospital of Patras, Patras, Greece. 18. Fourth Department of Pneumonology, General Hospital Sotiria, Athens, Greece. 19. Department of Cardiology, General Hospital of Elefsina Thriasio, Elefsina, Greece. 20. Therapeutics Department, Alexandra Hospital, Athens, Greece. 21. Second Medical Department, NIMTS Hospital, Athens, Greece. 22. Department of Internal Medicine, General Hospital of West Attica Agia Varvara, Athens, Greece. 23. Department of Cardiology, University of Patras Medical School, Patras, Greece. 24. Second Department of Cardiology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 25. Third Department of Cardiology, Hygeia Hospital, Athens, Greece. 26. Department of Cardiology, Ioannina University Hospital, University of Ioannina, Ioannina, Greece. 27. Department of Cardiology, University General Hospital of Larissa, Larissa, Greece. 28. Third Department of Cardiology, General Hospital Sotiria, National and Kapodistrian University of Athens, Athens, Greece. 29. Hospital Universitario y Politécnico La Fe, Valencia, Spain. 30. Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut. 31. Fourth Department of Internal Medicine, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece. 32. Icahn School of Medicine at Mount Sinai, New York, New York.
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 thecolchicine 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.
RCT Entities:
Importance: Severe acute respiratory syndrome coronavirus 2infection 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.
Authors: Eric J Lenze; Caline Mattar; Charles F Zorumski; Angela Stevens; Julie Schweiger; Ginger E Nicol; J Philip Miller; Lei Yang; Michael Yingling; Michael S Avidan; Angela M Reiersen Journal: JAMA Date: 2020-12-08 Impact factor: 56.272
Authors: Miguel Alejandro Pinzón; Santiago Ortiz; Héctor Holguín; Juan Felipe Betancur; Doris Cardona Arango; Henry Laniado; Carolina Arias Arias; Bernardo Muñoz; Julián Quiceno; Daniel Jaramillo; Zoraida Ramirez Journal: PLoS One Date: 2021-05-25 Impact factor: 3.240
Authors: Ruth K Topless; Amanda Phipps-Green; Megan Leask; Nicola Dalbeth; Lisa K Stamp; Philip C Robinson; Tony R Merriman Journal: ACR Open Rheumatol Date: 2021-04-15