Pharmacological Effects of Crushing Prasugrel in STEMI Patients

University of Florida

Status and phase

Completed

Phase 4

Conditions

Coronary Artery Disease

Treatments

Drug: prasugrel

Study type

Interventional

Funder types

Other

Identifiers

NCT02212028

Prasugrel-CRUSH

Details and patient eligibility

About

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.

Full 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.

Enrollment

52 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.