title: Design of the DOVE (Determining Effects of Platelet Inhibition on Vaso-Occlusive Events) trial: A global Phase 3 double-blind, randomized, placebo-controlled, multicenter study of the efficacy and safety of prasugrel in pediatric patients with sickle cell anemia utilizing a dose titration strategy.
abstract: BACKGROUND
  Sickle cell disease (SCD) is an inherited blood disorder characterized by painful vaso-occlusive crises (VOC) with limited treatment options, particularly for children. Emerging knowledge of the pathophysiology of SCD suggests antiplatelet therapies may hold promise for treatment of VOC. Multiple small studies have evaluated antiplatelet agents on the frequency of VOC with varying results, but there has not been an adequately powered study to definitively determine the effect of antiplatelet agents on VOC. Prasugrel, a third-generation thienopyridine that irreversibly inhibits platelet activation and aggregation, is approved in adults with acute coronary syndrome managed with percutaneous coronary intervention.
  
  
  METHODS
  Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) is a double-blind, randomized study with planned enrollment of >220 children from 14 countries across the Americas, Europe, Asia, and Africa, designed to test the hypothesis that prasugrel reduces the rate of VOC in children with sickle cell anemia (SCA) (homozygous hemoglobin S [HbSS] and hemoglobin Sβ(0) thalassemia [HbSβ(0)]). Secondary study endpoints include reductions in rate and intensity of vaso-occlusive pain as recorded in daily electronic diaries. Safety assessments include incidence of hemorrhagic events requiring medical intervention and treatment-emergent adverse events. DOVE incorporates a dose-titration strategy to reduce potential bleeding risks inherent with antiplatelet therapy while maintaining blinded treatment assignment.
  
  
  CONCLUSIONS
  DOVE presents a unique opportunity to determine whether antiplatelet therapy reduces frequency of patient-reported VOC and daily vaso-occlusive pain in a global study of children with SCA.
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, California.
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Hoppe
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, California.
authors.forename: Lori
authors.initials: L
authors.lastname: Styles
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Lori E
authors.initials: LE
authors.lastname: Heath
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Brown
authors.affiliation: King's College Hospital, London, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Rees
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Heeney
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*; D012107:Research Design; D014652:Vascular Diseases / Q000517:prevention & control*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride
keywords: acute chest syndrome; children; platelets; prasugrel; sickle cell anemia; vaso-occlusive pain