Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-function: a Validation Study
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Polymorphisms of the cytochrome P450 (CYP) 2C19 enzyme has been consistently shown to
      modulate clopidogrel response. Accordingly, the Food and Drug Administration (FDA) has issued
      a warning on the potential for reduced efficacy of clopidogrel among carriers of
      loss-of-function alleles (LOF) for CYP2C19 and suggest considering alternative antiplatelet
      therapies for these individuals.

      The pharmacodynamic (PD) effects of prasugrel and ticagrelor are not affected by CYP2C19
      genetic polymorphisms. However, to date there are no head-to-head PD comparisons between
      these agents among patients with different CYP2C19 genetic polymorphisms, which is currently
      under investigation in CAD patients undergoing PCI at UF Health-Jacksonville (UFJ 2014-12,
      NCT 02065479). In order to rule out play of chance findings, pharmacogenetic investigations
      require external validation cohorts to support the study findings. Therefore, the present
      randomized study is designed to serve as an external validation cohort conducted in patients
      with established CAD not undergoing PCI testing the non-inferiority in platelet reactivity of
      prasugrel versus ticagrelor among CYP2C19 LOF allele carriers.
    

Detailed description: 
      Therapeutic inhibition of platelet activation is essential for the management of ischemic
      cardiovascular disease. The use of platelet adenosine diphosphate (ADP) P2Y12 receptor
      antagonists (clopidogrel, prasugrel, and ticagrelor) in addition to aspirin are associated
      with a decrease in cardiovascular events in high-risk coronary artery disease (CAD) patients.
      Clopidogrel is the most broadly utilized P2Y12 receptor antagonist. However, among
      clopidogrel treated patients, there is broad variability in antiplatelet drug response which
      is known carry prognostic implications. Polymorphisms of the cytochrome P450 (CYP) 2C19
      enzyme has been consistently shown to modulate clopidogrel response. Accordingly, the Food
      and Drug Administration (FDA) has issued a warning on the potential for reduced efficacy of
      clopidogrel among carriers of loss-of-function alleles (LOF) for CYP2C19 and suggest
      considering alternative antiplatelet therapies for these individuals.

      The pharmacodynamic (PD) effects of prasugrel and ticagrelor are not affected by CYP2C19
      genetic polymorphisms. However, to date there are no head-to-head PD comparisons between
      these agents among patients with different CYP2C19 genetic polymorphisms which is currently
      under investigation in CAD patients undergoing PCI at UF Health-Jacksonville (UFJ 2014-12,
      NCT 02065479). In order to rule out play of chance findings, pharmacogenetic investigations
      require external validation cohorts to support the study findings. Therefore, the present
      randomized study is designed to serve as an external validation cohort conducted in patients
      with established CAD not undergoing PCI testing the non-inferiority in platelet reactivity of
      prasugrel versus ticagrelor among CYP2C19 LOF allele carriers.
    

Intervention name(s): Prasugrel; Ticagrelor
Intervention type(s): Drug; Drug
Intervention description(s): Maintenance dose will be maintained for 10±3 days.; Maintenance dose will be maintained for 10±3 days.
Other intervention name(s): Effient; Brilinta
Intervention MeSH terms: Ticagrelor; Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: clopidogrel; prasugrel; ticagrelor