Vorapaxar as an Add-On Antiplatelet Therapy in Patients With and Without Diabetes Mellitus

• Status: Completed
• Trial end date: 2019-02-14
• Target enrollment: 0
• Participant gender: All

Summary

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor, more frequently clopidogrel, represents the standard of care for the long-term secondary prevention of atherothrombotic events in patients with myocardial infarction (MI) or peripheral arterial disease (PAD). However, rates of ischemic recurrences remain high. Vorapaxar is a protease-activated receptor (PAR)-1 inhibitor, which exerts potent inhibition of thrombin-mediated platelet aggregation. Patients with diabetes mellitus (DM) are known to be at increased risk of recurrent atherothrombotic events, which translates into worse outcomes, despite the use of standard of care therapy. This is in part due to the hyperreactive platelet phenotype, which characterizes DM patients, and to inadequate response to oral antiplatelet agents, including clopidogrel. Therefore, vorapaxar is an attractive treatment option for DM patients with a prior MI. The pharmacodynamic (PD) effects of vorapaxar in DM patients and how these may differentiate from non-DM patients has not been explored. Further, the role of vorapaxar as part of a dual antithrombotic treatment regimen combined with clopidogrel (and stopping aspirin) represents another important area of clinical interest. The proposed prospective, parallel-design study conducted in patients post-MI or with PAD with and without DM will aim the assess the pharmacodynamic effects of vorapaxar in addition to standard DAPT with aspirin and clopidogrel as well as in combination with clopidogrel only following aspirin withdrawal.

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

Details

• Lead Sponsor: University of Florida
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Aspirin; Clopidogrel; Ticlopidine; Vorapaxar

Criteria

Inclusion criteria:

1. Patients with a prior MI between 2 weeks and 24 months or with PAD.

2. On DAPT with low-dose aspirin (81mg od) and clopidogrel (75mg od) as per standard-of-care for at least 14 days.

3. Age ≥ 18 years old.

Exclusion criteria:

1. History of acute coronary syndrome in the previous 2 weeks.

2. History of stroke, transient ischemic attack, or intracranial hemorrhage.

3. Active pathological bleeding, history of bleeding events or increased risk of bleeding.

4. Known severe hepatic impairment.

5. Use of strong cytochrome P450 3A4 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).

6. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban).

7. On treatment with any antiplatelet agent other than aspirin and clopidogrel in the past 14 days.

8. Creatinine clearance <30 mL/minute.

9. Platelet count <80x106/mL

10. Hemoglobin <10g/dL

11. Hemodynamic instability

12. Pregnant females