Influence of Vorapaxar on Thrombin Generation and Coagulability

Coronary Artery Disease Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02629367
• Other study ID #: INOVA-D1
• Status: Not yet recruiting
• Phase: Phase 4
• First received: December 10, 2015
• Last updated: December 11, 2015
• Start date: January 2016
• Est. completion date: March 2017

Study information

• Verified date: December 2015
• Source: Inova Health Care Services
• Contact: Kevin Bliden, MS, MBA
• Phone: 7037767702
• Email: Kevin.Bliden[@]inova.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Currently, there are no data available regarding the effect of vorapaxar on clot generation kinetics or TIP-FCS when added to standard of care antiplatelet regimens. Potential reduction of TIP-FCS and clot generation kinetics by vorapaxar may assist in our understanding of the mechanism of action and in personalizing therapy in high risk patients to effectively reduce recurrent thrombotic event occurrences. The objective of this study is to determine onset-, maintenance-, and offset-effect of vorapaxar on platelet-fibrin clot generation kinetics by thrombelastography (R, TIP-FCS, TG) and thrombin generation kinetics (Lag time, peak thrombin production, time to peak thrombin generation, and endogenous thrombin potential) in antiplatelet naïve patients and patients on mono and dual antiplatelet therapy. This is a phase IV, prospective cohort (4 groups), non-randomized, open label, pharmacodynamics, and safety investigation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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:

• Subject must present with multiple risk factors for CAD or PAD, such as high blood pressure, high cholesterol, diabetes, obesity, current smokers, or

• 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

• PAD as indicated by a history of intermittent claudication and

• a resting ankle/brachial index (ABI) of <0.85, or

• significant peripheral artery stenosis (>50%) documented by angiography or non-invasive testing by duplex ultrasound, or

• previous limb or foot amputation for arterial vascular disease (excludes trauma), or

• previous aorto-femoral bypass surgery, limb bypass surgery or percutaneous transluminal angioplasty of the iliac or infrainguinal arteries.

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, and for 2 months after stopping the medication.

5. The subject is able to read and give written informed consent

6. 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 (see Appendix) (but see note in text for exceptions).

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 of 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 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. Positive illicit drug screen

16. Current participation in any other study of investigational therapy, or participation in such a study within the last 30 days.

17. Known hypersensitivity to any component of the current investigational product.

18. Subject is a woman who is breast-feeding, pregnant, or who intends to become pregnant.

19. Subject is part of the staff personnel directly involved with this study, or is a family member of the investigational staff.

20. Known current substance abuse at the time of enrollment.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Vorapaxar

• Asprin

• Clopidogrel

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Inova Health Care Services

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet-fibrin clot generation kinetics		1 year	No
Primary	Thrombin generation kinetics		1 year	No
Primary	Measure of plasma biomarkers associated with haemostasis and inflammation		1 year	Yes