Pharmacological Effects of Crushing Prasugrel in STEMI Patients
| Status: | Completed |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/21/2016 |
| Start Date: | October 2014 |
| End Date: | August 2015 |
Pharmacodynamic and Pharmacokinetic Profiles of Prasugrel in Patients With ST Elevation Myocardial Infarction: A Randomized Comparison of Standard Versus Crushed Formulation
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.
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.
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.
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.
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.
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