Use of Novel Antithrombotic Agents for COVID-19: Systemic Summary of Ongoing Randomized Controlled Trials

Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA. Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran. Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Leon H. Charney Division of Cardiology, Department of Medicine, Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, 530 First Avenue, Skirball 9R, New York, NY, 10016, USA. Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA. Department of Internal Medicine &, Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands. Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada. Department of Medicine, University of Vermont Larner College of Medicine and University of Vermont Medical Center, Burlington, Vermont, USA. Department of Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine and University of Vermont Medical Center, Burlington, Vermont, USA. Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Clinical Trials Center, Cardiovascular Research Foundation, New York, NY, USA. Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, CT, USA.

Journal of thrombosis and haemostasis : JTH. 2021
PICO Summary

Population

Patients with COVID-19 (27 studies).

Intervention

Ten novel antithrombotic agents (including nafamostat, dociparstat, rNAPc2, and defibrotide).

Comparison

Heparin or placebo.

Outcome

The results from these trials have not been disseminated, yet. The studied drugs in the ongoing or completed randomised controlled trials include agents affecting the coagulation cascade, drugs affecting endothelial activation, and mixed acting agents.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is associated with macro and micro thrombosis, 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.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine