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JACC Basic Transl Sci
. 2021 Dec 8.
doi: 10.1016/j.jacbts.2021.09.013. Online ahead of print.
Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial
Thorsten M Leucker 1 , William O Osburn 1 , Paula Reventun 1 , Kimberley Smith 1 , Brian Claggett 2 , Bridget-Anne Kirwan 3 4 , Sophie de Brouwer 3 , Marlene S Williams 1 , Gary Gerstenblith 1 , David N Hager 5 , Michael B Streiff 6 , Scott D Solomon 2 , Charles J Lowenstein 1
Affiliations
- PMID: 34904132
- PMCID: PMC8653991
- DOI: 10.1016/j.jacbts.2021.09.013
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. (Crizanlizumab for Treating COVID-19 Vasculopathy [CRITICAL]; NCT04435184).
Keywords: CRP, C-reactive protein; IL, interleukin; TAT, thrombin antithrombin; TNF, tumor necrosis factor; VTE, venous thromboembolism; VWF, von Willebrand factor; coronavirus; crizanlizumab; endothelial; exocytosis; inflammation; thrombosis.