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
Intervention: Prasugrel; Ticagrelor
Intervention description: Maintenance dose will be maintained for 10±3 days.; Maintenance dose will be maintained for 10±3 days.
Intervention MeSH terms: Ticagrelor; Prasugrel Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective randomized
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: clopidogrel; prasugrel; ticagrelor

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.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients with CAD [defined as the presence of at least a 50% stenosis in a major
             epicardial vessel or major branch, or any prior coronary revascularization (PCI or
             coronary bypass graft surgery)] on treatment with either aspirin (81mg/day) or aspirin
             and clopidogrel (75m/day) for at least 30 days as per standard of care

          -  Participated in UFJ 2016-14 study with genetic buccal swab test and have at least one
             CYP 2C19 LOF allele (CYP2C19*2 and CYP2C19*3)

          -  Women of childbearing age must use reliable birth control (i.e. oral contraceptives)
             while participating in the study.

        Exclusion criteria:

          -  Known allergies to prasugrel or ticagrelor

          -  Weight <60kg

          -  Considered at high risk for bleeding

          -  Currently active bleeding

          -  History of ischemic or hemorrhagic stroke or transient ischemic attack, or
             intracranial hemorrhage

          -  Known severe hepatic dysfunction

          -  On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran,
             apixaban, rivaroxaban)

          -  Platelet count <80x106/mL

          -  Hemoglobin <10 g/dL.

          -  Creatinine Clearance <30 mL/minute

          -  Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker
             protection.

          -  Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction
             with ticagrelor): CYP3A Inhibitors (ketoconazole, itraconazole, voriconazole,
             clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir,
             and telithromycin ) and CYP3A Inducers (rifampin, phenytoin, carbamazepine, and
             phenobarbital)

          -  Pregnant or breastfeeding females