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Published in: Journal of Hematology & Oncology 1/2013

Open Access 01-12-2013 | Research

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

Authors: Ted Wun, Denis Soulieres, Andrew L Frelinger, Lakshmanan Krishnamurti, Enrico M Novelli, Abdullah Kutlar, Kenneth I Ataga, Charles L Knupp, Lillian E McMahon, John J Strouse, Chunmei Zhou, Lori E Heath, Chuke E Nwachuku, Joseph A Jakubowski, Jeffrey S Riesmeyer, Kenneth J Winters

Published in: Journal of Hematology & Oncology | Issue 1/2013

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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.
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Metadata
Title
A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease
Authors
Ted Wun
Denis Soulieres
Andrew L Frelinger
Lakshmanan Krishnamurti
Enrico M Novelli
Abdullah Kutlar
Kenneth I Ataga
Charles L Knupp
Lillian E McMahon
John J Strouse
Chunmei Zhou
Lori E Heath
Chuke E Nwachuku
Joseph A Jakubowski
Jeffrey S Riesmeyer
Kenneth J Winters
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2013
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-6-17

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