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Trial record 21 of 512 for:    ASPIRIN AND P2

Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor (VORA-PRATIC)

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: NCT02545933
Recruitment Status : Active, not recruiting
First Posted : September 10, 2015
Last Update Posted : December 11, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE September 8, 2015
First Posted Date  ICMJE September 10, 2015
Last Update Posted Date December 11, 2019
Actual Study Start Date  ICMJE February 2016
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2015)
Maximal platelet aggregation [ Time Frame: 30 days ]
The primary end point of our study is the comparison of maximal platelet aggregation measured by light transmittance aggregometry between DAPT and DAPT plus vorapaxar after 30 treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2015)
Comparison of maximal Platelet aggregation measured by light transmittance aggregometry [ Time Frame: 30 days ]
The secondary end point of our study is the comparison of maximal platelet aggregation measured by light transmittance aggregometry between vorapaxar in addition to prasugrel or ticagrelor and vorapaxar in addition to standard DAPT
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 Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor
Official Title  ICMJE Adjunctive Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With New Generation P2Y12 Receptor Inhibitors Prasugrel and Ticagrelor (VORA-PRATIC): A Prospective, Randomized, Pharmacodynamic Study
Brief Summary Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the standard of care for the long-term secondary prevention of atherothrombotic events in patients with myocardial infarction (MI). However, rates of ischemic recurrences remain high, which may be in part due to the fact that other platelet signaling pathways, such as thrombin-induced platelet aggregation, continue to be activated. Vorapaxar is a protease-activated receptor (PAR)-1 inhibitor, which exerts potent inhibition of thrombin-mediated platelet aggregation. It is approved for clinical use by the Food and Drug Administration for the reduction of thrombotic cardiovascular events in patients with a history of MI or with peripheral arterial disease. However, to date clinical trial experience with vorapaxar has been almost exclusively with the P2Y12 receptor inhibitor clopidogrel and the effects of vorapaxar in combination with antiplatelet therapy including prasugrel or ticagrelor, is largely unexplored. Further, the role of vorapaxar as part of a dual antithrombotic treatment regimen, in addition to a novel P2Y12 receptor inhibitor, with withdrawal of aspirin, represents another important area of clinical interest as it has the potential to maximize ischemic protection while reducing the risk of bleeding. The proposed prospective, randomized, parallel-design, open label, study conducted in a real world clinical setting of post-MI patients will aim to assess the pharmacodynamic effects of vorapaxar in addition to antiplatelet therapy with a novel P2Y12 receptor inhibitor (prasugrel or ticagrelor) with and without aspirin.
Detailed Description Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the standard of care for the long-term secondary prevention of atherothrombotic events in patients with myocardial infarction (MI). The novel P2Y12 receptor inhibitors prasugrel and ticagrelor are characterized by more prompt, potent, and predictable antiplatelet effects compared with clopidogrel and are associated with a greater reduction of ischemic events in acute coronary syndrome patients. However, rates of ischemic recurrences remain high, which may be in part due to the fact that other platelet signaling pathways, such as thrombin-induced platelet aggregation, continue to be activated. Vorapaxar is a novel, orally active, competitive and slowly reversible protease-activated receptor (PAR)-1 inhibitor, which exerts potent inhibition of thrombin-mediated platelet aggregation. It is approved for clinical use by the Food and Drug Administration for the reduction of thrombotic cardiovascular events in patients with a history of MI or with peripheral arterial disease. A large-scale clinical trial showed that the use of vorapaxar (2.5 mg once/daily) in addition to standard antiplatelet therapy (including aspirin and a P2Y12 receptor inhibitor) was effective in the secondary prevention of recurrent thrombotic events in patients with previous atherothrombosis, in particular in patients with prior MI, at the expense of an increase in major bleeding. However, to date clinical trial experience with vorapaxar has been almost exclusively with the P2Y12 receptor inhibitor clopidogrel and the effects of vorapaxar in combination with state-of-the-art antiplatelet therapy in the post-MI setting, including prasugrel or ticagrelor, is largely unexplored. This may indeed represent a limitation for the uptake of vorapaxar in modern day clinical practice where these agents are being more broadly utilized. Further, the role of vorapaxar as part of a dual antithrombotic treatment regimen, in addition to a novel P2Y12 receptor inhibitor, with withdrawal of aspirin, represents another important area of clinical interest as it has the potential to maximize ischemic protection while reducing the risk of bleeding. The proposed prospective, randomized, parallel-design, open label, study conducted in a real world clinical setting of post-MI patients will aim to assess the pharmacodynamic effects of vorapaxar in addition to antiplatelet therapy with a novel P2Y12 receptor inhibitor (prasugrel or ticagrelor) with and without aspirin. Pharmacodynamic assessments will be performed at multiple time points and with different assays exploring multiple pathways of platelet aggregation. Exploratory assessments on the safety of such approach will also be evaluated.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myocardial Infarction
Intervention  ICMJE
  • Drug: Prasugrel
    Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)
    Other Name: Effient
  • Drug: Vorapaxar
    Vorapaxar will be administered at the dose of 2.5mg once daily
    Other Name: Zontivity
  • Drug: Aspirin
    Aspirin will be administered at the dose of 81mg once daily
    Other Name: ASA
  • Drug: Ticagrelor
    Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)
    Other Name: Brilinta
Study Arms  ICMJE
  • Experimental: DAPT plus vorapaxar
    Aspirin plus prasugrel or ticagrelor plus vorapaxar 2.5mg od
    Interventions:
    • Drug: Prasugrel
    • Drug: Vorapaxar
    • Drug: Aspirin
    • Drug: Ticagrelor
  • Experimental: Prasugrel/ticagrelor plus vorapaxar
    Prasugrel or ticagrelor plus vorapaxar 2.5mg od
    Interventions:
    • Drug: Prasugrel
    • Drug: Vorapaxar
    • Drug: Ticagrelor
  • Active Comparator: DAPT
    Aspirin in addition to prasugrel or ticagrelor
    Interventions:
    • Drug: Prasugrel
    • Drug: Aspirin
    • Drug: Ticagrelor
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 9, 2015)
126
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Patients with a prior MI within the previous 2 weeks to 12 months.
  2. On DAPT with low-dose aspirin (81mg od) and either prasugrel (10mg od) or ticagrelor (90mg bid) as per standard-of-care for at least 2 weeks.
  3. Free from bleeding and ischemic events after the index MI event.
  4. Age between 18 and 75 years old.

Exclusion criteria:

  1. History of stroke, transient ischemic attack, or intracranial hemorrhage.
  2. Active pathological bleeding, history of bleeding events or increased risk of bleeding.
  3. Known severe hepatic impairment.
  4. Age >75 years.
  5. Body weight <60 Kg.
  6. Use of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) or inducers (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin).
  7. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban).
  8. On treatment with any antiplatelet agent other than aspirin, prasugrel and ticagrelor in the past 14 days.
  9. Creatinine clearance <30 mL/minute.
  10. Platelet count <80x106/mL
  11. Hemoglobin <10g/dL
  12. Hemodynamic instability
  13. Pregnant females
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 NCT02545933
Other Study ID Numbers  ICMJE IIS 53376
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida College of Medicine-Jacksonville
PRS Account University of Florida
Verification Date December 2019

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