Pharmacological Effects of Crushing Prasugrel in STEMI Patients

• ClinicalTrials.gov Identifier: NCT02212028
• Recruitment Status: Completed
• First Posted: August 8, 2014
• Results First Posted: December 28, 2016
• Last Update Posted: December 28, 2016
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: prasugrel	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacodynamic and Pharmacokinetic Profiles of Prasugrel in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Standard Versus Crushed Formulation
• Study Start Date: October 2014
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Prasugrel crush; Prasugrel 60mg loading dose as crushed tablets	Drug: prasugrel; the effects of whole tablets versus crushed tablets will be compared; Other Name: Effient
Active Comparator: Prasugrel tablets; Prasugrel 60 mg loading dose as whole tablets	Drug: prasugrel; the effects of whole tablets versus crushed tablets will be compared; Other Name: Effient

Outcome Measures

Primary Outcome Measures :

1. P2Y12 Reaction Units (PRU) [ Time Frame: 2 hrs ]
   The primary end-point of the study is the comparison in platelet reactivity expressed as PRU determined by VerifyNow P2Y12 between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration

Secondary Outcome Measures :

1. Platelet Reactivity Index (PRI) [ Time Frame: 2 hrs ]
   The secondary end-point of the study is the comparison in platelet reactivity expressed as PRI determined by whole blood vasodilator-stimulated phosphoprotein (VASP) between prasugrel 60 mg and crushed prasugrel 60 mg at 2 hours after LD administration

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

University of Florida

Jacksonville, Florida, United States, 32209

Sponsors and Collaborators

University of Florida

Investigators

• Principal Investigator: Dominick Angiolillo; University of Florida

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02212028 History of Changes
• Other Study ID Numbers: Prasugrel-CRUSH
• First Posted: August 8, 2014
• Results First Posted: December 28, 2016
• Last Update Posted: December 28, 2016
• Last Verified: August 2015

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Florida:

ST-elevation myocardial infarction; prasugrel; pharmacodynamic; pharmacokinetic

Additional relevant MeSH terms:

Coronary Artery Disease; ST Elevation Myocardial Infarction; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Myocardial Infarction; Prasugrel Hydrochloride; Platelet Aggregation Inhibitors