Display options
Cite
Leucker TM, Osburn WO, Reventun P, et al. Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial. JACC Basic Transl Sci. 2021;6(12):935-945doi: 10.1016/j.jacbts.2021.09.013.
Leucker, T. M., Osburn, W. O., Reventun, P., Smith, K., Claggett, B., Kirwan, B. A., de Brouwer, S., Williams, M. S., Gerstenblith, G., Hager, D. N., Streiff, M. B., Solomon, S. D., & Lowenstein, C. J. (2021). Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial. JACC. Basic to translational science, 6(12), 935-945. https://doi.org/10.1016/j.jacbts.2021.09.013
Leucker, Thorsten M, et al. "Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial." JACC. Basic to translational science vol. 6,12 (2021): 935-945. doi: https://doi.org/10.1016/j.jacbts.2021.09.013
Leucker TM, Osburn WO, Reventun P, Smith K, Claggett B, Kirwan BA, de Brouwer S, Williams MS, Gerstenblith G, Hager DN, Streiff MB, Solomon SD, Lowenstein CJ. Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial. JACC Basic Transl Sci. 2021 Dec;6(12):935-945. doi: 10.1016/j.jacbts.2021.09.013. Epub 2021 Dec 08. PMID: 34904132; PMCID: PMC8653991.
Copy Download .nbib Format: NLM
Share it on

JACC Basic Transl Sci. 2021 Dec;6(12):935-945. doi: 10.1016/j.jacbts.2021.09.013. Epub 2021 Dec 08.

Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial.

JACC. Basic to translational science

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, Charles J Lowenstein

Affiliations

  1. Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  2. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  3. SOCAR Research SA, Nyon, Switzerland.
  4. Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, Bloomsbury, London, United Kingdom.
  5. Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  6. Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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).

© 2021 The Authors.

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

Conflict of interest statement

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 a

References

  1. Blood Coagul Fibrinolysis. 2013 Sep;24(6):608-12 - PubMed
  2. Lancet Haematol. 2020 Aug;7(8):e575-e582 - PubMed
  3. Lancet. 2020 May 2;395(10234):1417-1418 - PubMed
  4. Cardiovasc Res. 2020 Dec 1;116(14):2177-2184 - PubMed
  5. Thromb Haemost. 1990 Oct 22;64(2):192-5 - PubMed
  6. Eur Heart J. 2020 Sep 1;41(32):3038-3044 - PubMed
  7. Life Sci. 2021 Jul 15;277:119634 - PubMed
  8. Thromb Res. 1990 May 1;58(3):331-41 - PubMed
  9. Lancet Infect Dis. 2020 Aug;20(8):e192-e197 - PubMed
  10. N Engl J Med. 2017 Feb 2;376(5):429-439 - PubMed
  11. Circulation. 2020 Oct 27;142(17):1609-1611 - PubMed
  12. Am J Hematol. 2020 Dec;95(12):1479-1485 - PubMed
  13. Blood. 2015 Jul 9;126(2):242-6 - PubMed
  14. Circ Res. 2020 Sep 11;127(7):945-947 - PubMed
  15. Blood. 2009 Mar 26;113(13):2878-87 - PubMed
  16. Circulation. 1986 Nov;74(5):1027-36 - PubMed
  17. Inflamm Res. 2020 Dec;69(12):1181-1189 - PubMed
  18. N Engl J Med. 2020 Jul 9;383(2):120-128 - PubMed
  19. Blood. 2020 Jun 4;135(23):2033-2040 - PubMed
  20. Mod Pathol. 2021 Aug;34(8):1456-1467 - PubMed
  21. Arterioscler Thromb Vasc Biol. 2021 May 5;41(5):1760-1773 - PubMed
  22. Lancet Microbe. 2020 Nov;1(7):e290-e299 - PubMed
  23. Arterioscler Thromb Vasc Biol. 2020 Oct;40(10):2539-2547 - PubMed
  24. Circulation. 2021 Mar 30;143(13):1338-1340 - PubMed
  25. Circulation. 1987 Jun;75(6):1200-3 - PubMed
  26. J Med Vasc. 2020 Sep;45(5):268-274 - PubMed
  27. J Am Coll Cardiol. 2017 Nov 7;70(19):2411-2420 - PubMed
  28. Crit Care. 2021 Feb 19;25(1):74 - PubMed
  29. Int J Mol Sci. 2021 Jul 26;22(15): - PubMed

Publication Types