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Influence of Vorapaxar on Thrombin Generation and Coagulability

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03207451
Recruitment Status : Completed
First Posted : July 2, 2017
Last Update Posted : August 22, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Inova Health Care Services

Tracking Information
First Submitted Date  ICMJE January 4, 2017
First Posted Date  ICMJE July 2, 2017
Last Update Posted Date August 22, 2018
Actual Study Start Date  ICMJE January 1, 2016
Actual Primary Completion Date July 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2017)
  • Effects of Vorapaxar on Platelet Aggregation as measured by Light Transmission Aggregometry. Final and Maximum percent of aggregation will be measured in response to ADP, Collagen, and Thrombin Receptor Activating Protein (TRAP or SFFLRN). [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on Clot Formation as measured by thrombelastography. [ Time Frame: 8 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2017)
  • Effects of Vorapaxar on Thrombin Generation as measured by Calibrated Automatic Thrombogram Assay. [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma C-reactive protein (CRP). [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma fibrinogen. [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma von Willebrand factor (vWF). [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma interleukin (IL)-6. [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma p-selectin. [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma plasminogen activator inhibitor (PAI)-1. [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on plasma matrix metalloproteinase (MMP)-9. [ Time Frame: 8 weeks ]
  • Effects of Vorapaxar on Urinary TxB2. [ Time Frame: 8 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Influence of Vorapaxar on Thrombin Generation and Coagulability
Official Title  ICMJE Not Provided
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE
  • Coronary Artery Disease
  • Peripheral Vascular Disease
  • Myocardial Infarction
Intervention  ICMJE
  • Drug: Vorapaxar
    Vorapaxar is the principle study drug and will be given to all subjects.
    Other Name: Group 1
  • Drug: Vorapaxar and Aspirin
    Subjects in groups 3 will be on Aspirin when they begin Vorapaxar therapy.
    Other Name: Group 3
  • Drug: Vorapaxar and Clopidogrel
    Subjects in groups 2 will be on Clopidogrel when they begin Vorapaxar therapy.
    Other Name: Group 2
  • Drug: Vorapaxar, Aspirin, and Clopidogrel
    Subjects in groups 4 will be on both Aspirin and Clopidogrel when they begin Vorapaxar therapy.
    Other Name: Group 4
Study Arms  ICMJE
  • Experimental: Vorapaxar
    Subjects with multiple risk factors and antiplatelet naïve to receive Vorapaxar.
    Intervention: Drug: Vorapaxar
  • Experimental: Vorapaxar and Clopidogrel
    Subjects with 600 mg Load /75mg QD Clopidogrel QD for ≥ 7 days to receive Vorapaxar
    Intervention: Drug: Vorapaxar and Clopidogrel
  • Experimental: Vorapaxar and Aspirin
    Subjects with 81mg QD Aspirin to receive Vorapaxar
    Intervention: Drug: Vorapaxar and Aspirin
  • Experimental: Vorapaxar, Aspirin, and Clopidogrel
    Subjects with 81 mg QD Aspirin+75mg QD Clopidogrel to receive Vorapaxar.
    Intervention: Drug: Vorapaxar, Aspirin, and Clopidogrel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 21, 2018)
90
Original Estimated Enrollment  ICMJE
 (submitted: June 30, 2017)
100
Actual Study Completion Date  ICMJE August 1, 2018
Actual Primary Completion Date July 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03207451
Other Study ID Numbers  ICMJE 15-2051
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Inova Health Care Services
Study Sponsor  ICMJE Inova Health Care Services
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Paul Gurbel, MD Inova Health System
PRS Account Inova Health Care Services
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP