Photo courtesy of St. Jude
Children’s Research Hospital
Treatment with the antiplatelet agent prasugrel does not significantly reduce the rate of pain crises or severe lung complications in children with sickle cell disease (SCD), according to one of the largest and most geographically diverse international trials on SCD to date.
The DOVE trial was a double blind, randomized, placebo-controlled phase 3 study conducted at 51 sites across 13 nations in the Americas, Europe, the Middle East, Asia, and Africa.
“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 the wide range of countries where the disease occurs is hugely significant,” said Carolyn Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California.
“The logistical challenges that we addressed in designing and implementing the study can serve as a model for future research.”
The results of the study were published in NEJM. The research was sponsored by Daiichi Sankyo Company, Ltd. and Eli Lilly and Company.
The goal of the DOVE trial was to determine whether prasugrel could significantly reduce the rate of vaso-occlusive crises (VOCs)—defined as pain crises or acute chest syndrome—in children with SCD.
The trial enrolled 341 patients. About half of them (n=170) received daily oral prasugrel for between 9 and 24 months at individualized, blinded doses intended to maintain a selected target range of platelet activity. The remaining patients received a placebo.
All patients were monitored for VOCs prompting medical visits and for any increased risk of bleeding due to reduced platelet activity. In addition, patients 4 years old and older kept a daily electronic pain diary to aid in the reporting of painful events between visits.
At the end of the study period, there was no significant difference between the treatment arms in the overall rate of VOCs. The rate was 2.3 episodes per person-year in the prasugrel arm and 2.8 episodes per person-year in the placebo arm (P=0.12).
Similarly, prasugrel did not have a significant effect on the trial’s secondary outcome measures—VOC-related hospitalization rate, duration of hospitalization, time between VOCs, incidence of ischemic attack or ischemic stroke, transfusion rate, rate of pain, intensity of pain, use of analgesics, or missed school due to SCD-related pain.
The data did reveal a trend toward reduced VOC rates among patients ages 12 to 18 (P=0.06) and among patients who were not taking hydroxyurea (P=0.06). However, these trends were not statistically significant and require further research to determine their validity.
The investigators noted no adverse events related to prasugrel.
“Even though prasugrel did not achieve significant results, the findings should not detract from the fact that this team successfully completed a rigorous, sophisticated trial in a disease where the barriers to conducting large-scale international, patient-focused research are quite high,” said Matthew M. Heeney, MD, of the Dana–Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts.
To conduct the study successfully on such a broad geographical scale, the investigators had to address several obstacles, such as varying standards of care, local technological resources, and infrastructure challenges, such as a lack of reliable electrical power.
