title: A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease.
abstract: BACKGROUND
  Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study.
  
  
  METHODS
  The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients.
  
  
  RESULTS
  There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events.
  
  
  CONCLUSIONS
  Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.
authors: University of California, Davis Cancer Center, 4501 X St,, Ste, 3016, Sacramento, CA, 95817, USA. twun@ucdavis.edu
authors: Ted
authors: T
authors: Wun
authors: Denis
authors: D
authors: Soulieres
authors: Andrew L
authors: AL
authors: Frelinger
authors: Lakshmanan
authors: L
authors: Krishnamurti
authors: Enrico M
authors: EM
authors: Novelli
authors: Abdullah
authors: A
authors: Kutlar
authors: Kenneth I
authors: KI
authors: Ataga
authors: Charles L
authors: CL
authors: Knupp
authors: Lillian E
authors: LE
authors: McMahon
authors: John J
authors: JJ
authors: Strouse
authors: Chunmei
authors: C
authors: Zhou
authors: Lori E
authors: LE
authors: Heath
authors: Chuke E
authors: CE
authors: Nwachuku
authors: Joseph A
authors: JA
authors: Jakubowski
authors: Jeffrey S
authors: JS
authors: Riesmeyer
authors: Kenneth J
authors: KJ
authors: Winters
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D014408:Biomarkers, Tumor / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D010146:Pain / Q000517:prevention & control*; D010750:Phosphoproteins / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D011379:Prognosis; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D055815:Young Adult; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000068799:Prasugrel Hydrochloride