ARTICLE: Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial
AUTHORS: Thorsten M. Leucker, William O. Osburn, Paula Reventun, Kimberley Smith, Brian Claggett, Bridget-Anne Kirwan, Sophie de Brouwer, Marlene S. Williams, Gary Gerstenblith, David N. Hager, Michael B. Streiff, Scott D. Solomon, and Charles J. Lowenstein
JOURNAL: J Am Coll Cardiol Basic Trans Science. Dec 08, 2021. Epublished DOI: 10.1016/j.jacbts.2021.09.013
Highlights
- Severe COVID-19 is characterized by vascular inflammation and thrombosis, including elevations of P-selectin, a marker released by activated endothelial cells that mediates vascular inflammation.
- We tested the effect of crizanlizumab, an antibody to P-selectin, on biomarkers of inflammation and thrombosis in patients with COVID-19 in a randomized, placebo-controlled, double-blind clinical trial.
- Crizanlizumab decreased soluble P-selectin levels in patients with COVID-19.
- Crizanlizumab increased D-dimer and decreased prothrombin fragment 2.1 in patients with COVID-19.
- Crizanlizumab may induce endogenous thrombolysis in the setting of COVID-19.
Summary
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)
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