Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor

• Status: Completed
• Trial end date: 2020-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Florida
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Aspirin; Prasugrel Hydrochloride; Ticagrelor; Vorapaxar

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 Cytochrome P450 3A 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