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

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

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Article number17
JournalJournal of Hematology and Oncology
Volume6
Issue number1
DOIs
StatePublished - Feb 19 2013

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Sickle Cell Anemia
Placebos
Platelet Activation
P-Selectin
Platelet Aggregation Inhibitors
Pain
Blood Platelets
Biomarkers
Safety
Prasugrel Hydrochloride

Keywords

  • Platelet function
  • Prasugrel
  • Sickle cell disease
  • Thienopyridine

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease. / Wun, Ted; Soulieres, Denis; Frelinger, Andrew L.; Krishnamurti, Lakshmanan; Novelli, Enrico M.; Kutlar, Abdullah; Ataga, Kenneth I.; Knupp, Charles L.; McMahon, Lillian E.; Strouse, John J.; Zhou, Chunmei; Heath, Lori E.; Nwachuku, Chuke E.; Jakubowski, Joseph A.; Riesmeyer, Jeffrey S.; Winters, Kenneth J.

In: Journal of Hematology and Oncology, Vol. 6, No. 1, 17, 19.02.2013.

Research output: Contribution to journalArticle

Wun, T, Soulieres, D, Frelinger, AL, Krishnamurti, L, Novelli, EM, Kutlar, A, Ataga, KI, Knupp, CL, McMahon, LE, Strouse, JJ, Zhou, C, Heath, LE, Nwachuku, CE, Jakubowski, JA, Riesmeyer, JS & Winters, KJ 2013, 'A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease', Journal of Hematology and Oncology, vol. 6, no. 1, 17. https://doi.org/10.1186/1756-8722-6-17
Wun, Ted ; Soulieres, Denis ; Frelinger, Andrew L. ; Krishnamurti, Lakshmanan ; Novelli, Enrico M. ; Kutlar, Abdullah ; Ataga, Kenneth I. ; Knupp, Charles L. ; McMahon, Lillian E. ; Strouse, John J. ; Zhou, Chunmei ; Heath, Lori E. ; Nwachuku, Chuke E. ; Jakubowski, Joseph A. ; Riesmeyer, Jeffrey S. ; Winters, Kenneth J. / A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease. In: Journal of Hematology and Oncology. 2013 ; Vol. 6, No. 1.
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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{\circledR} 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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AU - Wun, Ted

AU - Soulieres, Denis

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AU - Krishnamurti, Lakshmanan

AU - Novelli, Enrico M.

AU - Kutlar, Abdullah

AU - Ataga, Kenneth I.

AU - Knupp, Charles L.

AU - McMahon, Lillian E.

AU - Strouse, John J.

AU - Zhou, Chunmei

AU - Heath, Lori E.

AU - Nwachuku, Chuke E.

AU - Jakubowski, Joseph A.

AU - Riesmeyer, Jeffrey S.

AU - Winters, Kenneth J.

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N2 - 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.

AB - 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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