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Use of Novel Antithrombotic Agents for Covid-19: Systematic Summary of Ongoing Randomized Controlled Trials Publisher Pubmed



Talasaz AH1, 2, 3 ; Sadeghipour P4 ; Aghakouchakzadeh M1 ; Kakavand H1 ; Ariannejad H2 ; Connors JM5 ; Hunt BJ6 ; Berger JS7 ; Van Tassell BW3, 8 ; Middeldorp S9 ; Piazza G10 ; Weitz JI11, 12 ; Cushman M13, 14 ; Lip GYH15, 16 Show All Authors
Authors
  1. Talasaz AH1, 2, 3
  2. Sadeghipour P4
  3. Aghakouchakzadeh M1
  4. Kakavand H1
  5. Ariannejad H2
  6. Connors JM5
  7. Hunt BJ6
  8. Berger JS7
  9. Van Tassell BW3, 8
  10. Middeldorp S9
  11. Piazza G10
  12. Weitz JI11, 12
  13. Cushman M13, 14
  14. Lip GYH15, 16
  15. Goldhaber SZ10
  16. Bikdeli B10, 17, 18
Show Affiliations
Authors Affiliations
  1. 1. Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, United States
  4. 4. Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  6. 6. Haemostasis and Thrombosis Centre, St Thomas' Hospital, London, United Kingdom
  7. 7. Leon H. Charney Division of Cardiology, Department of Medicine, Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, New York, NY, United States
  8. 8. Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, United States
  9. 9. Department of Internal Medicine & Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, Netherlands
  10. 10. Cardiovascular Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  11. 11. Department of Medicine, McMaster University, Hamilton, ON, Canada
  12. 12. Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada
  13. 13. Department of Medicine, University of Vermont Larner College of Medicine and University of Vermont Medical Center, Burlington, VT, United States
  14. 14. Department of Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine and University of Vermont Medical Center, Burlington, VT, United States
  15. 15. Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom
  16. 16. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  17. 17. Clinical Trials Center, Cardiovascular Research Foundation, New York, NY, United States
  18. 18. Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, CT, United States

Source: Journal of Thrombosis and Haemostasis Published:2021


Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with macro- and micro-thromboses, which are triggered by endothelial cell activation, coagulopathy, and uncontrolled inflammatory response. Conventional antithrombotic agents are under assessment in dozens of randomized controlled trials (RCTs) in patients with COVID-19, with preliminary results not demonstrating benefit in several studies. Objectives: Given the possibility that more novel agents with antithrombotic effects may have a potential utility for management of patients with COVID-19, we assessed ongoing RCTs including these agents with their potential mechanism of action in this population. Methods: We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to identify RCTs of novel antithrombotic agents in patients with COVID-19. Results: Based on a systematic literature search, 27 RCTs with 10 novel antithrombotic agents (including nafamostat, dociparstat, rNAPc2, and defibrotide) were identified. The results from these trials have not been disseminated yet. The studied drugs in the ongoing or completed RCTs include agents affecting the coagulation cascade, drugs affecting endothelial activation, and mixed acting agents. Their postulated antithrombotic mechanisms of action and their potential impact on patient management are summarized. Conclusion: Some novel antithrombotic agents have pleiotropic anti-inflammatory and antiviral effects, which may help reduce the viral load or fibrosis, and improve oxygenation. Results from ongoing RCTs will elucidate their actual role in the management of patients with COVID-19. © 2021 International Society on Thrombosis and Haemostasis
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