Influence of Vorapaxar on Thrombin Generation and Coagulability

• Status: Completed
• Trial end date: 2018-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Inova Health Care Services
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Aspirin; Clopidogrel; Vorapaxar

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.