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Open Access Research

A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

Ted Wun1*, Denis Soulieres2, Andrew L Frelinger3, Lakshmanan Krishnamurti4, Enrico M Novelli5, Abdullah Kutlar6, Kenneth I Ataga7, Charles L Knupp8, Lillian E McMahon9, John J Strouse10, Chunmei Zhou11, Lori E Heath11, Chuke E Nwachuku12, Joseph A Jakubowski11, Jeffrey S Riesmeyer11 and Kenneth J Winters11

Author Affiliations

1 University of California, Davis Cancer Center, 4501 X St., Ste. 3016, Sacramento, CA, 95817, USA

2 CHUM-Notre-Dame, Montreal, QC, Canada

3 Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

4 Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

5 University of Pittsburg Medical Center, Pittsburg, PA, USA

6 Medical College of Georgia, Augusta, GA, USA

7 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

8 ECU-Brody School of Medicine, Greenville, NC, USA

9 Boston Medical Center, Boston, MA, USA

10 The Johns Hopkins University School of Medicine, Baltimore, MD, USA

11 Eli Lilly and Company, Indianapolis, IN, USA

12 Daiichi Sankyo, Inc, Edison, NJ, USA

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Journal of Hematology & Oncology 2013, 6:17  doi:10.1186/1756-8722-6-17

Published: 17 February 2013

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.

Keywords:
Prasugrel; Sickle cell disease; Thienopyridine; Platelet function