Treatment with prasugrel did not significantly reduce the rate of vaso-occlusive crisis in children and adolescents with sickle cell anemia, according to the results of a phase 3 trial.
Safety outcomes appeared similar among children and adolescents assigned prasugrel (Effient; Daiichi Sankyo, Eli Lilly) and those assigned placebo, results showed.
Sickle cell anemia is an inherited blood disorder that affects 100 million adults and children worldwide, including approximately 100,000 people in the U.S., according to study background.
The disease is characterized by severe vaso-occlusive crises, for which few treatment options exist. Research suggests that platelets mediate intercellular adhesion and thrombosis during vaso-occlusion.
Thus, Carolyn C. Hoppe, MD, pediatric hematologist at University of California, San Francisco, and Children’s Hospital of Oakland Research Institute, and colleagues sought to study the efficacy of the antiplatelet agent prasugrel for the treatment of vaso-occlusive events.
Hoppe and colleagues conducted a multinational, randomized, double blind trial of children aged 2 years to 17 years with sickle cell anemia. The study enrolled 341 patients (mean age, 10.6 ± 4.3 years) from 13 countries, whom the researchers randomly assigned oral prasugrel (n = 171) or placebo (n = 170) for a period of 9 months to 24 months.
The rate of vaso-occlusive crises — determine by the researchers through a composite of painful crises and acute chest syndrome — served as the primary endpoint. Key secondary endpoints included the rate and intensity of sickle cell–associated pain, the rate of hospitalization for vaso-occlusion and safety.
The researchers observed a similar rate of vaso-occlusive crises per person-year in both study arms (2.3 vs. 2.77; rate ratio = 0.83; 95% CI, 0.66-1.05).
Further, treatment with prasugrel did not appear to confer a significant effect on any of the key secondary endpoints, which also included the rate of red-cell transfusion, the rate of analgesic use and the rate of absence from school due to sickle cell–associated pain.
Researchers also evaluated platelet reactivity using a whole-blood assay (VerifyNow P2Y12, Accriva Diagnostics) that reports results in terms of P2Y12 reaction units (PRUs). After adjustment to the final maintenance dose, platelet reactivity appeared significantly lower in the prasugrel arm (mean difference, –72.4 PRUs; 95% CI, –83.7 to –61.1).
The researchers observed no significant difference in the incidence of hemorrhagic events requiring medical intervention, or of hemorrhagic or nonhemorrhagic adverse events, between study arms. Three children died during the study period (prasugrel, n = 1; placebo, n = 2); however, the researchers determined that their deaths were not treatment related.
“Although we were disappointed that prasugrel does not appear to ease the suffering of children with sickle cell disease, the fact that this study incorporated patients in a wide range of countries where the disease occurs is hugely significant,” Hoppe said in a press release. “The logistical challenges that we addressed in designing and implementing this study can serve as a model for future research.” – by Cameron Kelsall
Disclosure: Daiichi Sankyo and Eli Lilly provided funding for this study. Hoppe reports grants, personal fees and nonfinancial support from Eli Lilly during the conduct of this study. Please see the full study for a list of all other researchers’ relevant financial disclosures.