Vorapaxar on Thrombin Generation and Coagulability

NCT03207451 | Completed Phase 4 Results

• 1 other identifier: 15-2051
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Coronary Artery Disease; Peripheral Vascular Disease; Myocardial Infarction

Keywords

Anti-Platelet Therapy

Outcome Measures

Primary Outcomes (2)

• Effects of Vorapaxar on 15 μmol/L SFLLRN (PAR-1 Activating Peptide) Induced Platelet Aggregation

  15 μmol/L SFLLRN (PAR-1 activating peptide) induced maximum platelet aggregation at 30 days after treatment with Vorapaxar

  30 days after treatment with Vorapaxar

• Effects of Vorapaxar on Thrombin Induced Platelet-fibrin Clot Strength (TIP-FCS)

  Thrombin induced platelet-fibrin clot strength (TIP-FCS) at 30 days after treatment with Vorapaxar as measured by thromboelastography.

  30 days after treatment with Vorapaxar

Secondary Outcomes (1)

• Effects of Vorapaxar on Von Willebrand Factor (vWF).

  30 Days after treatment with Vorapaxar

Study Arms (4)

Vorapaxar

EXPERIMENTAL

Subjects with multiple risk factors and antiplatelet naïve to receive Vorapaxar.

Drug: Vorapaxar

Vorapaxar and Clopidogrel

EXPERIMENTAL

Subjects with 600 mg Load /75mg QD Clopidogrel QD for ≥ 7 days to receive Vorapaxar

Drug: Vorapaxar and Clopidogrel

Vorapaxar and Aspirin

EXPERIMENTAL

Subjects with 81mg QD Aspirin to receive Vorapaxar

Drug: Vorapaxar and Aspirin

Vorapaxar, Aspirin, and Clopidogrel

EXPERIMENTAL

Subjects with 81 mg QD Aspirin+75mg QD Clopidogrel to receive Vorapaxar.

Drug: Vorapaxar, Aspirin, and Clopidogrel

Interventions

Vorapaxar DRUG

Vorapaxar is the principle study drug and will be given to all subjects.

Also known as: Group 1

Vorapaxar

Vorapaxar and Aspirin DRUG

Subjects in groups 3 will be on Aspirin when they begin Vorapaxar therapy.

Also known as: Group 3

Vorapaxar and Aspirin

Vorapaxar and Clopidogrel DRUG

Subjects in groups 2 will be on Clopidogrel when they begin Vorapaxar therapy.

Also known as: Group 2

Vorapaxar and Clopidogrel

Vorapaxar, Aspirin, and Clopidogrel DRUG

Subjects in groups 4 will be on both Aspirin and Clopidogrel when they begin Vorapaxar therapy.

Also known as: Group 4

Vorapaxar, Aspirin, and Clopidogrel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject may be of either sex and of any race, and must be between 18 and 75 years of age.
• 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
• 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
• Subject must be willing and able to give appropriate, informed consent.
• 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.
• 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).

You may not qualify if:

• Clinically unstable at the time of enrollment.
• Any planned coronary revascularization or peripheral intervention.
• Concurrent or anticipated treatment with warfarin (or derivatives, e.g., phenprocoumon), oral factor Xa inhibitor, or oral direct thrombin inhibitor after enrollment.
• 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)
• History of a bleeding, or evidence of active abnormal bleeding.
• History at any time of intracranial hemorrhage, intracranial or spinal cord surgery, or a central nervous system tumor or aneurysm.
• Documented sustained severe hypertension (systolic blood pressure \>200 mmHg or diastolic blood pressure \>110 mmHg) at enrollment or within the previous 10 days.
• Severe valvular heart disease, as defined by the American College of Cardiology /American Heart Association.
• 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.
• History within 30 days before enrollment or of TIA and ischemic (presumed thrombotic) stroke/CVA.
• Known platelet count \<100,000/mm3 within 30 days before enrollment.
• 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" \[2xULN\]).
• 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.
• Any serious medical comorbidity (e.g., active malignancy) such that the subject's life expectancy is \<24 months.
• Current participation in any other study of investigational therapy, or participation in such a study within the last 30 days.

Sponsors & Collaborators

• Inova Health Care Services: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Inova Fairfax Hospital

Falls Church, Virginia, 22207, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Peripheral Vascular Diseases; Myocardial Infarction

Interventions

vorapaxar; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Inova Health System

kevin.bliden@inova.org

443-244-1497

Study Officials

• Paul Gurbel, MD

  Inova Health Care Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: July 2, 2017
• Study Start: January 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 18, 2022
• Results First Posted: August 18, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)