Clinical trial NCT02212028: Pharmacological Effects of Crushing Prasugrel in STEMI Patients
Official title: Pharmacodynamic and Pharmacokinetic Profiles of Prasugrel in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Standard Versus Crushed Formulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: ST-elevation myocardial infarction
prasugrel
pharmacodynamic
pharmacokinetic
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2014-08-08
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: P2Y12 Reaction Units (PRU)
timeFrame: 2 hrs
Secondary outcomes:
measure: Platelet Reactivity Index (PRI)
timeFrame: 2 hrs
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Dominick Angiolillo
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.