Pharmacological Effects of Crushing Prasugrel in STEMI Patients

NCT ID: NCT02212028

Last Updated: 2016-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-08-31

Brief 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.

Detailed 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.

Conditions

Coronary Artery Disease

Keywords

ST-elevation myocardial infarction; prasugrel; pharmacodynamic; pharmacokinetic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prasugrel crush

Prasugrel 60mg loading dose as crushed tablets

Group Type: EXPERIMENTAL

prasugrel

Intervention Type: DRUG

the effects of whole tablets versus crushed tablets will be compared

Prasugrel tablets

Prasugrel 60 mg loading dose as whole tablets

Group Type: ACTIVE_COMPARATOR

prasugrel

Intervention Type: DRUG

the effects of whole tablets versus crushed tablets will be compared

Interventions

prasugrel

the effects of whole tablets versus crushed tablets will be compared

Intervention Type: DRUG

Other Intervention Names

Effient

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick Angiolillo

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

References

Rollini F, Franchi F, Hu J, Kureti M, Aggarwal N, Durairaj A, Park Y, Seawell M, Cox-Alomar P, Zenni MM, Guzman LA, Suryadevara S, Antoun P, Bass TA, Angiolillo DJ. Crushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Intervention: The CRUSH Study. J Am Coll Cardiol. 2016 May 3;67(17):1994-2004. doi: 10.1016/j.jacc.2016.02.045. Epub 2016 Mar 21.

Reference Type: DERIVED

PMID: 27012781 (View on PubMed)

Other Identifiers

Prasugrel-CRUSH

Identifier Type: -

Identifier Source: org_study_id