1. Effect of the P-Selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial.
- Author
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Solomon, Scott, Lowenstein, Charles, Bhatt, Ankeet, Peikert, Alexander, Vardeny, Orly, Kosiborod, Mikhail, Berger, Jeffrey, Reynolds, Harmony, Mavromichalis, Stephanie, Barytol, Anya, Althouse, Andrew, Luther, James, Leifer, Eric, Kindzelski, Andrei, Cushman, Mary, Gong, Michelle, Khatri, Pooja, Kim, Keri, Baumann Kreuziger, Lisa, Wahid, Lana, Kirwan, Bridget-Anne, Geraci, Mark, Neal, Matthew, Hochman, Judith, and Kornblith, Lucy
- Subjects
COVID-19 ,P-selectin ,crizanlizumab ,Humans ,COVID-19 ,SARS-CoV-2 ,P-Selectin ,Endothelial Cells ,Treatment Outcome - Abstract
BACKGROUND: COVID-19 has been associated with endothelial injury, resultant microvascular inflammation and thrombosis. Activated endothelial cells release and express P-selectin and von Willebrand factor, both of which are elevated in severe COVID-19 and may be implicated in the disease pathophysiology. We hypothesized that crizanlizumab, a humanized monoclonal antibody to P-selectin, would reduce morbidity and death in patients hospitalized for COVID-19. METHODS: An international, adaptive, randomized controlled platform trial, funded by the National Heart, Lung, and Blood Institute, randomly assigned 422 patients hospitalized with COVID-19 with moderate or severe illness to receive either a single infusion of the P-selectin inhibitor crizanlizumab (at a dose of 5 mg/kg) plus standard of care or standard of care alone in an open-label 1:1 ratio. The primary outcome was organ support-free days, evaluated on an ordinal scale consisting of the number of days alive free of organ support through the first 21 days after trial entry. RESULTS: The study was stopped for futility by the data safety monitoring committee. Among 421 randomized patients with known 21-day outcomes, 163 patients (77%) randomized to the crizanlizumab plus standard-of-care arm did not require any respiratory or cardiovascular organ support compared with 169 (80%) in the standard-of-care-alone arm. The adjusted odds ratio for the effect of crizanlizumab on organ support-free days was 0.70 (95% CI, 0.43-1.16), where an odds ratio >1 indicates treatment benefit, yielding a posterior probability of futility (odds ratio 1] = 0.879). CONCLUSIONS: Crizanlizumab, a P-selectin inhibitor, did not result in improvement in organ support-free days in patients hospitalized with COVID-19. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04505774.
- Published
- 2023