Pharmacological Effects of Crushing Prasugrel in STEMI Patients
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; ST Elevation Myocardial Infarction
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): prasugrel
Intervention type(s): Drug
Intervention description(s): the effects of whole tablets versus crushed tablets will be compared
Other intervention name(s): Effient
Intervention MeSH terms: Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ST-elevation myocardial infarction; prasugrel; pharmacodynamic; pharmacokinetic