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Trial record 40 of 1255 for:    ASPIRIN AND Platelet Aggregation

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 : June 6, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Florida

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.

Condition or disease Intervention/treatment Phase
Myocardial Infarction Drug: Prasugrel Drug: Vorapaxar Drug: Aspirin Drug: Ticagrelor Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 2016
Actual Primary Completion Date : May 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: DAPT plus vorapaxar
Aspirin plus prasugrel or ticagrelor plus vorapaxar 2.5mg od
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

Experimental: Prasugrel/ticagrelor plus vorapaxar
Prasugrel or ticagrelor plus vorapaxar 2.5mg od
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: Ticagrelor
Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)
Other Name: Brilinta

Active Comparator: DAPT
Aspirin in addition to prasugrel or ticagrelor
Drug: Prasugrel
Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)
Other Name: Effient

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02545933


Locations
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United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida College of Medicine-Jacksonville

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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02545933     History of Changes
Other Study ID Numbers: IIS 53376
First Posted: September 10, 2015    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:
prasugrel
ticagrelor
vorapaxar

Additional relevant MeSH terms:
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Aspirin
Platelet Aggregation Inhibitors
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Ticagrelor
Prasugrel Hydrochloride
Vorapaxar
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists