Pharmacological Effects of Crushing Prasugrel in STEMI Patients

Coronary Artery Disease Clinical Trial

Official title:

Pharmacodynamic and Pharmacokinetic Profiles of Prasugrel in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Standard Versus Crushed Formulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02212028
• Other study ID #: Prasugrel-CRUSH
• Status: Completed
• Phase: Phase 4
• First received: August 6, 2014
• Last updated: October 1, 2015
• Start date: October 2014
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Prasugrel has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Prasugrel is approved in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) at a dosage of 60 mg loading dose (LD) followed by 10 mg/day. However, a delay in the onset of its antiplatelet effects in this particular setting has been consistently shown. administration of clopidogrel and ticagrelor crushed tablets has been tested and a faster and greater bioavailability compared to the whole tablets has been observed. However, if the administration of a crushed prasugrel LD may overcome the above limitation is still unknown and represents the aim of our study. The proposed investigation will have a prospective, randomized, design in which STEMI patients undergoing primary PCI will be randomized to receive two different formulation of prasugrel LD (60 mg whole tablets and 60 mg crushed tablets). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that crushed LD regiment will achieve more prompt and enhanced platelet inhibitory effects.

Description:

Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the cornerstone of treatment for prevention of thrombotic events in patients with acute coronary syndromes (ACS). Prasugrel, a third generation thienopyridine, is an orally administered prodrug that needs single-step hepatic biotransformation into its active metabolite to irreversibly block the P2Y12 receptor. Prasugrel has shown to be superior to clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Prasugrel is approved in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) at a dosage of 60 mg loading dose (LD) followed by 10 mg/day. However, a delay in the onset of its antiplatelet effects in this particular setting has been consistently shown. The STEMI setting is characterized by conditions, such as impaired absorption and hepatic metabolism, patients either intubated, in shock or unable to swallow, which may affect the pharmacoki¬netic and pharmacodynamic effects of orally administered antiplatelet drugs. The administration of clopidogrel and ticagrelor crushed tablets has been tested and a faster and greater bioavailability compared to the whole tablets has been observed. However, if the administration of a crushed prasugrel LD may overcome the above limitation is still unknown and represents the aim of our study. The proposed investigation will have a prospective, randomized, design in which STEMI patients undergoing primary PCI will be randomized to receive two different formulation of prasugrel LD (60 mg whole tablets and 60 mg crushed tablets). Pharmacodynamic testing will be performed at several time points to test our study hypothesis that crushed LD regiment will achieve more prompt and enhanced platelet inhibitory effects. This study will provide insights on the pharmacodynamic effects of crushed prasugrel LD and will help clinicians choose the most appropriate treatment to avoid complications related to inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary PCI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• Patients with ST-elevation myocardial infarction undergoing primary PCI

• Age between 18 and 75 years old

Exclusion criteria:

• Age >75 years

• Weight <60 Kg

• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 7 days

• Known allergies to aspirin or prasugrel

• Considered at high risk for bleeding

• History of ischemic or hemorrhagic stroke or transient ischemic attack

• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, apixaban)

• Treatment with IIb/IIIa glycoprotein inhibitors

• Fibrinolytics within 24 hours

• Known blood dyscrasia or bleeding diathesis

• Known platelet count <80x106/mL

• Known hemoglobin <10 g/dL

• Active bleeding

• Hemodynamic instability

• Known creatinine clearance <30 mL/minute

• Known severe hepatic dysfunction

• Pregnant females*

• Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Drug:
• prasugrel
the effects of whole tablets versus crushed tablets will be compared

Locations

Country	Name	City	State
United States	University of Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet reactivity unit	The primary end-point of the study is the comparison of the PRU determined by VerifyNow P2Y12 between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration	2 hrs	No