Vorapaxar on Thrombin Generation and Coagulability
Condition: Coronary Artery Disease; Peripheral Vascular Disease; Myocardial Infarction
MeSH terms: Coronary Artery Disease; Myocardial Infarction; Vascular Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Infarction
Intervention: Vorapaxar; Vorapaxar and Aspirin; Vorapaxar and Clopidogrel; Vorapaxar, Aspirin, and Clopidogrel
Intervention description: Vorapaxar is the principle study drug and will be given to all subjects.; Subjects in groups 3 will be on Aspirin when they begin Vorapaxar therapy.; Subjects in groups 2 will be on Clopidogrel when they begin Vorapaxar therapy.; Subjects in groups 4 will be on both Aspirin and Clopidogrel when they begin Vorapaxar therapy.
Intervention MeSH terms: Aspirin; Clopidogrel; Vorapaxar
Phase: Phase 4
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Anti-Platelet Therapy

Summary:

      This investigation will be conducted in patients 18-75 years of age with multiple coronary
      artery disease risk factors (antiplatelet naïve patients) and patients with prior MI or PVD
      on antiplatelet therapy. Pharmacodynamics will be assessed at multiple time points to assess
      onset-, maintenance-, and offset-effect of vorapaxar on thrombin generation, platelet
      reactivity, and plasma/platelet endothelial and inflammatory biomarkers. Safety assessment
      will be assessed throughout the study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject may be of either sex and of any race, and must be between 18 and 75 years of
             age.

          2. Subject must have multiple risk factors of developing atherosclerosis, or evidence of
             a history of atherosclerosis involving the coronary or peripheral vascular systems as
             follows:

               1. Subject must present with multiple risk factors for CAD or PAD, such as high
                  blood pressure, high cholesterol, diabetes, obesity, current smokers, or

               2. CAD as indicated by a history of presumed spontaneous MI (hospitalized with final
                  diagnosis of MI, excluding periprocedural or definite secondary MI [e.g., due to
                  profound anemia or hypertensive emergency, troponin increase in sepsis]) at least
                  1 month prior to enrollment, or

               3. PAD as indicated by a history of intermittent claudication and

             i. a resting ankle/brachial index (ABI) of <0.85, or ii. significant peripheral artery
             stenosis (>50%) documented by angiography or non-invasive testing by duplex
             ultrasound, or iii. previous limb or foot amputation for arterial vascular disease
             (excludes trauma), or iv. previous aorto-femoral bypass surgery, limb bypass surgery
             or percutaneous transluminal angioplasty of the iliac or infrainguinal arteries, or v.
             subjects with asymptomatic carotid artery disease ii. amputation, peripheral bypass,
             or peripheral angioplasty of the extremities secondary to ischemia

          3. Subject must be willing and able to give appropriate, informed consent.

          4. Women of childbearing potential must have a negative pregnancy test prior to
             enrollment and immediately before drug administration and agree to use at least two
             methods of medically approved barrier contraception, or a hormonal contraceptive to
             prevent pregnancy throughout the study.A woman of child-bearing potential who is
             currently sexually active must agree to use a medically accepted method of
             contraception prior to screening, while receiving protocol-specified medication, and
             for 2 months after stopping the medication.

          5. The subject is able to read and give written informed consent and has signed and dated
             an informed consent document and authorization permitting release of personal health
             information approved by the Investigator's Institutional Review Board (IRB).

        Exclusion Criteria:

          1. Clinically unstable at the time of enrollment.

          2. Any planned coronary revascularization or peripheral intervention.

          3. Concurrent or anticipated treatment with warfarin (or derivatives, e.g.,
             phenprocoumon), oral factor Xa inhibitor, or oral direct thrombin inhibitor after
             enrollment.

          4. Concurrent or anticipated treatment with a potent inducer (e.g., rifampin) or potent
             inhibitor (eg, ketoconazole, erythromycin) of CYP3A4 isoenzymes (but see note in text
             for exceptions). Make list of CYP3A4 inhibitors and inducers (appendix)

          5. History of a bleeding, or evidence of active abnormal bleeding.

          6. History at any time of intracranial hemorrhage, intracranial or spinal cord surgery,
             or a central nervous system tumor or aneurysm.

          7. Documented sustained severe hypertension (systolic blood pressure >200 mmHg or
             diastolic blood pressure >110 mmHg) at enrollment or within the previous 10 days.

          8. Severe valvular heart disease, as defined by the American College of Cardiology
             /American Heart Association.

          9. History within 30 days before enrollment ofof major invasive surgeries (other than
             mentioned above), is anticipating one during the course of their study participation,
             or is planning to have one within 1 month post dosing with the study drug.

         10. History within 30 days before enrollment or of TIA and ischemic (presumed thrombotic)
             stroke/CVA.

         11. Known platelet count <100,000/mm3 within 30 days before enrollment.

         12. Known active hepatobiliary disease, or known unexplained persistent increase in serum
             alanine aminotransferase (ALT) or aspartate aminotransferase (AST) activity to two
             times or more the upper limit of the reference range (upper limit of "normal"
             [2xULN]).

         13. Any serious illness or any condition that the investigator feels would (a) pose a
             significant hazard to the subject if investigational therapy were initiated, or (b)
             would limit the prognosis of the subject, regardless of investigational therapy.

         14. Any serious medical comorbidity (e.g., active malignancy) such that the subject's life
             expectancy is <24 months.

         15. Current participation in any other study of investigational therapy, or participation
             in such a study within the last 30 days.

         16. Known hypersensitivity to any component of the current investigational product.

         17. Subject is a woman who is breast-feeding, pregnant, or who intends to become pregnant.

         18. Subject is part of the staff personnel directly involved with this study, or is a
             family member of the investigational staff.

         19. Known current substance abuse at the time of enrollment.