Primary Investigator: Kul Aggarwal, MD
Study Coordinator: Alisa Lau-Sieckman, RN
Status: Closed to enrollment; follow-up continues
Study Title: A multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of SCH530348 in addition to standard of care in subjects with a history of atherosclerotic disease: Thrombin receptor antagonist for secondary prevention of atherothrombotic ischemic events
Purpose: The primary objective is to evaluate the hypothesis that SCH530348 added to standard of care alone, as measured by the composite of cardiovascular death, myocardial infarction (MI), stroke and urgent coronary revascularization.
1. Subject may be of either sex and any race, and must be at least 18 years old.
2. Subject must have evidence or a history of atherosclerosis involving the coronary, cerebral, or peripheral vascular systems as follows:
a. Coronary artery disease (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]) ≥2 weeks but ≤12 months prior.
b. Ischemic (presumed thrombotic) cardiovascular disease (CVD) as indicated by a history of ischemic stroke (hospitalized with final diagnosis of nonhemorrhagic stroke) ≥2 weeks but ≤12 months prior.
c. PAD as indicated by a history of intermittent claudication and
i. an ankle/brachial index (ABI) of <0.85,
ii. amputation, peripheral bypass, or peripheral angioplasty of the extremities secondary to ischemia.
3. 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 two months after stopping the medication.
4. A woman of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study.
The subject will be excluded from entry if ANY of the criteria listed below are met:
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.
(NOTE: A subject who was not using warfarin/derivatives and for whom use was not anticipated, but who subsequently requires warfarin/derivatives after randomized assignment of study drug may continue treatment with warfarin/derivatives and randomized study drug)
4. Concurrent or anticipated treatment with a potent inducer (e.g., rifampin) or potent inhibitor (e.g., ketoconazole, erythromycin) of CYP3A4 isoenzymes (a more detailed list will be supplied in separate instructions to the investigator).
(NOTE: A subject who was not using a potent CYP3A4 inducer or potent inhibitor and/or for whom such therapy was not anticipated, but who subsequently requires such therapy after randomized assignment of study drug may receive such therapy.
5. History of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before enrollment.
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.
9. History within two weeks prior to enrollment of major surgery other than mentioned above or of ischemic (presumed thrombotic) stroke.
10. Known platelet count <100,000/mm3 within 30 days before enrollment.
11. Active hepatobiliary disease, or 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]).
12. Any serious illness or any condition that the investigator feels would:
(a) pose a significant hazard to the subject if investigational therapy were initiated,
(b) would limit the prognosis of the subject, regardless of investigational therapy.
13. Any serious medical comorbidity (e.g., active malignancy) such that the subject's life expectancy is <24 months.
14. Known hypersensitivity to any component of the current investigational product.
15. Subject is a woman who is breast-feeding, pregnant, or who intends to become pregnant (affirm that a female subject of child-bearing potential is not pregnant before enrollment [method of affirmation left to the discretion of the investigator]).
16. Subject is part of the staff personnel directly involved with this study, or is a family member of the investigational staff.
17. Known current substance abuse at the time of enrollment.
1. Call Alisa Lau-Sieckman (beeper: 573-443-9259) and/or on-call research nurse (on-call beeper 573-499-8084) or Dr. Aggarwal if subject is admitted to the hospital or for any questions regarding study medication.