@article{c9b6f0863c8144ae9677c431cb2d1145,
title = "Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial",
abstract = "COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19.",
keywords = "coronavirus, crizanlizumab, endothelial, exocytosis, inflammation, thrombosis",
author = "Leucker, {Thorsten M.} and Osburn, {William O.} and Paula Reventun and Kimberley Smith and Brian Claggett and Kirwan, {Bridget Anne} and {de Brouwer}, Sophie and Williams, {Marlene S.} and Gary Gerstenblith and Hager, {David N.} and Streiff, {Michael B.} and Solomon, {Scott D.} and Lowenstein, {Charles J.}",
note = "Funding Information: This work was funded by Novartis. Dr Leucker has received grants from the American Heart Association Career Development Award (19CDA34760040), the Johns Hopkins Center for AIDS Research (P30AI094189 and 1704611701), the Johns Hopkins Older Americans Independence Center (P30AG021334), and Amgen; and is a coinvestigator of the CRITICAL trial, which tests the safety and efficacy of a P-selectin inhibitor in patients with COVID-19. Dr Gerstenblith has received grant support from Amgen, Novartis, and the National Institutes of Health; is also a member of the Data and Safety Monitoring Board for clinical trials sponsored by Salubris, Blade Therapeutics, and Capricor. Dr Hager has received a grant from Incyte Corporation for conduct of the RUXCOVID-DEVENT trial; has previously received salary support from the Marcus Foundation for conduct of the VICTAS trial; and is currently a coinvestigator in the Centers for Disease Control and Prevention–funded Influenza and Other Viruses in the Acutely Ill Network (75D30121F00002). Dr Streiff is supported by contracts from Patient Centered Outcomes Research Institute entitled “Preventing Venous Thromboembolism: Empowering Patients and Enabling Patient-Centered Care via Health Information Technology” (CE-12-11-4489), “Preventing Venous Thromboembolism (VTE): Engaging Patients to Reduce Preventable Harm From Missed/Refused Doses of VTE Prophylaxis” (DI-1603-34596), “Implementing Best-Practice, Patient-Centered Venous Thromboembolism (VTE) Prevention in Trauma Centers” (DI-2019C3-17859); is supported by a grant from the Agency for Healthcare Research and Quality (1R01HS024547) entitled “Individualized Performance Feedback on Venous Thromboembolism Prevention Practice,” a contract from Patient Centered Outcomes Research Institute entitled “Preventing Venous Thromboembolism (VTE): Engaging Patients to Reduce Preventable Harm From Missed/Refused Doses of VTE Prophylaxis,” a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute (R21HL129028) entitled “Analysis of the Impact of Missed Doses of Venous Thromboembolism Prophylaxis,” and a grant from the Agency for Healthcare Research and Quality (R18HS025341) titled “Disseminating an Evidence-Based Venous Thromboembolism Prevention Bundle” (all of these grants/contract support studies outside the submitted work); has received research funding from Boehringer-Ingelheim, Janssen, Novo Nordisk, Roche, Sanofi, and Tremeau; has consulted for Bayer, Bristol Myers Squibb, Coagulo Medical Technologies, Janssen, Pfizer, and Portola; has received honoraria for CME presentations from Bayer, Pfizer, and Portola (outside the submitted work); and has given expert witness testimony in various medical malpractice cases. Dr Solomon has received grants and personal fees from Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cytokinetics, Gilead, GlaxoSmithKline, MyoKardia, Novartis, and Theracos; grants from Bellerophon, Celladon, Eidos, Ionis, Lone Star Heart, Mesoblast, the National Institutes of Health/National Heart, Lung, and Blood Institute, and Sanofi Pasteur; personal fees from Akros, AoBiome, Arena, Cardiac Dimensions, Cardurion, Corvia, Daichi-Sankyo, Dinaqor, Ironwood, Janssen, Merck, Quantum Genomics, Roche, Takeda, Tenaya, Tremeau; and personal fees from Moderna (outside the submitted work) and is a coinvestigator of the CRITICAL trial, which tests the safety and efficacy of a P-selectin inhibitor in patients with COVID-19. Dr Lowenstein has received research grants from Novartis; the National Institutes of Health/National Heart, Lung, and Blood Institute (R01 HL134894, R61 HL14179); and the Michel Mirowski M.D. Professorship in Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Funding Information: The authors gratefully acknowledge the work of members of the Johns Hopkins Investigational Drug Service, Laura Wachter, PharmD, and Lisa Ruppel, PharmD. We gratefully acknowledge the assistance of Shannon Kelley, BS, Johns Hopkins Hospital. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = dec,
doi = "10.1016/j.jacbts.2021.09.013",
language = "English (US)",
volume = "6",
pages = "935--945",
journal = "JACC: Basic to Translational Science",
issn = "2452-302X",
publisher = "Elsevier Inc.",
number = "12",
}