Crizanlizumab fails to reduce organ support-free days for inpatients with COVID-19
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Key takeaways:
- Researchers did not observe significant differences in organ-support free days with or without crizanlizumab.
- Inhibition of P-selectin appeared unlikely to benefit patients with moderate to severe COVID-19.
Crizanlizumab did not reduce organ support-free days or in-hospital mortality among patients hospitalized with moderate to severe COVID-19, according to study results presented at International Society on Thrombosis and Hemostasis Congress.
The study, simultaneously published in Circulation, stopped early due to futility.
Rationale and methods
“COVID-19 is associated with endothelial injury, microvascular inflammation and thrombosis,” Charles J. Lowenstein, MD, chief of cardiology at Johns Hopkins University School of Medicine, and colleagues wrote in the study abstract. “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.”
The international, adaptive, randomized-controlled platform trial included 421 patients hospitalized with moderate or severe COVID-19.
Researchers assigned patients 1:1 to either a single fusion of crizanlizumab (Adakveo, Novartis) dosed at 5 mg/kg plus standard-of-care treatment or standard of care alone.
They hypothesized that crizanlizumab would reduce morbidity and mortality among the study population.
Organ support-free days, evaluated on an ordinal scale that consisted of the number of days alive free of organ support through the first 21 days after study entry, served as the primary outcome.
Findings
The data safety monitoring committee stopped the study early due to futility.
Results showed that 77% of patients assigned crizanlizumab plus standard of care did not require any respiratory or cardiovascular organ support compared with 80% of patients assigned standard of care only.
Researchers observed an adjusted OR of 0.7 (95% credible interval [CrI], 0.43-1.16) for the effect of crizanlizumab on organ support-free days, which yielded a posterior probability of futility of 98%.
Thirty-seven deaths (17.5%) occurred in the crizanlizumab group compared with 27 (12.8%) in the standard-of-care group (HR = 1.42; 95% CrI, 0.9-2.36).
Implications
The findings do not support the use of crizanlizumab in reducing complications among patients hospitalized with COVID-19, the researchers wrote.
“Inhibition of P-selectin is unlikely to benefit patients with moderate to severe COVID-19,” they added.
References:
- Lowenstein C, et al. Abstract LB 01.5. Presented at: International Society on Thrombosis and Hemostasis Congress; June 24-28, 2023; Montreal.
- Solomon SD, et al. Circulation. 2023;doi:10.1161/CIRCULATIONAHA.123.065190.
Collapse
Lowenstein C, et al. Abstract LB 01.5. Presented at: The International Society on Thrombosis and Hemostasis’ annual meeting; June 24-28, 2023; Montreal.
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