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

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 - J Hematol Oncol (2013)

Bottom Line: 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.In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of California, Davis Cancer Center, 4501 X St,, Ste, 3016, Sacramento, CA, 95817, USA. twun@ucdavis.edu

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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Related in: MedlinePlus

Effect of prasugrel vs. placebo on biomarkers of disease-related platelet activation. A. Percent of platelets positive for platelet surface P-selectin, B. Plasma soluble P-selectin, C. Serum TXB2, D. plasma soluble CD40L. Prasugrel = black bars; placebo = grey bars. Results are mean ± SD
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Figure 5: Effect of prasugrel vs. placebo on biomarkers of disease-related platelet activation. A. Percent of platelets positive for platelet surface P-selectin, B. Plasma soluble P-selectin, C. Serum TXB2, D. plasma soluble CD40L. Prasugrel = black bars; placebo = grey bars. Results are mean ± SD

Mentions: Numerous studies have shown that platelets are activated in SCD patients [10,12] and that markers of platelet activation are associated with complications [13,14]. The effects of prasugrel on platelet activation were measured with both cellular (platelet P-selectin) and soluble biomarkers (TXB2, soluble CD40L, and soluble P-selectin). There were statistically significant decreases in platelet P-selectin and soluble P-selectin at both days 10 and 30 in the prasugrel arm compared to placebo. The decreases also reached statistical significance for TXB2 at day 10 and for soluble CD40L at day 30 in the prasugrel arm compared to placebo (Figure 5). Therefore, prasugrel was shown not only to inhibit platelet function, but also to decrease platelet activation in patients with SCD.


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

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 - J Hematol Oncol (2013)

Effect of prasugrel vs. placebo on biomarkers of disease-related platelet activation. A. Percent of platelets positive for platelet surface P-selectin, B. Plasma soluble P-selectin, C. Serum TXB2, D. plasma soluble CD40L. Prasugrel = black bars; placebo = grey bars. Results are mean ± SD
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585853&req=5

Figure 5: Effect of prasugrel vs. placebo on biomarkers of disease-related platelet activation. A. Percent of platelets positive for platelet surface P-selectin, B. Plasma soluble P-selectin, C. Serum TXB2, D. plasma soluble CD40L. Prasugrel = black bars; placebo = grey bars. Results are mean ± SD
Mentions: Numerous studies have shown that platelets are activated in SCD patients [10,12] and that markers of platelet activation are associated with complications [13,14]. The effects of prasugrel on platelet activation were measured with both cellular (platelet P-selectin) and soluble biomarkers (TXB2, soluble CD40L, and soluble P-selectin). There were statistically significant decreases in platelet P-selectin and soluble P-selectin at both days 10 and 30 in the prasugrel arm compared to placebo. The decreases also reached statistical significance for TXB2 at day 10 and for soluble CD40L at day 30 in the prasugrel arm compared to placebo (Figure 5). Therefore, prasugrel was shown not only to inhibit platelet function, but also to decrease platelet activation in patients with SCD.

Bottom Line: 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.In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of California, Davis Cancer Center, 4501 X St,, Ste, 3016, Sacramento, CA, 95817, USA. twun@ucdavis.edu

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.

Show MeSH
Related in: MedlinePlus