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

NCT02545933 | Completed Phase 4 Results FDA Drug

• 1 other identifier: IIS 53376
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Infarction

Keywords

prasugrel; ticagrelor; vorapaxar

Outcome Measures

Primary Outcomes (1)

• Maximal Platelet Aggregation

  The primary end point of our study is the comparison of maximal platelet aggregation measured by light transmittance aggregometry using CAT (collagen-ADP-TRAP) between DAPT and DAPT plus vorapaxar after 30 days of treatment.

  30 days

Study Arms (3)

DAPT plus vorapaxar

EXPERIMENTAL

Aspirin plus prasugrel or ticagrelor plus vorapaxar 2.5mg od

Drug: Prasugrel; Drug: Vorapaxar; Drug: Aspirin; Drug: Ticagrelor

Prasugrel/ticagrelor plus vorapaxar

EXPERIMENTAL

Prasugrel or ticagrelor plus vorapaxar 2.5mg od

Drug: Prasugrel; Drug: Vorapaxar; Drug: Ticagrelor

DAPT

ACTIVE COMPARATOR

Aspirin in addition to prasugrel or ticagrelor

Drug: Prasugrel; Drug: Aspirin; Drug: Ticagrelor

Interventions

Prasugrel DRUG

Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)

Also known as: Effient

DAPT; DAPT plus vorapaxar; Prasugrel/ticagrelor plus vorapaxar

Vorapaxar DRUG

Vorapaxar will be administered at the dose of 2.5mg once daily

Also known as: Zontivity

DAPT plus vorapaxar; Prasugrel/ticagrelor plus vorapaxar

Aspirin DRUG

Aspirin will be administered at the dose of 81mg once daily

Also known as: ASA (acetylsalicylic acid)

DAPT; DAPT plus vorapaxar

Ticagrelor DRUG

Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)

Also known as: Brilinta

DAPT; DAPT plus vorapaxar; Prasugrel/ticagrelor plus vorapaxar

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a prior MI within the previous 2 weeks to 12 months.
• 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.
• Free from bleeding and ischemic events after the index MI event.
• Age between 18 and 75 years old.

You may not qualify if:

• History of stroke, transient ischemic attack, or intracranial hemorrhage.
• Active pathological bleeding, history of bleeding events or increased risk of bleeding.
• Known severe hepatic impairment.
• Age \>75 years.
• Body weight \<60 Kg.
• 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).
• On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban).
• On treatment with any antiplatelet agent other than aspirin, prasugrel and ticagrelor in the past 14 days.
• Creatinine clearance \<30 mL/minute.
• Platelet count \<80x106/mL
• Hemoglobin \<10g/dL
• Hemodynamic instability
• Pregnant females

Sponsors & Collaborators

• University of Florida: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• Franchi F, Rollini F, Faz G, Rivas JR, Rivas A, Agarwal M, Briceno M, Wali M, Nawaz A, Silva G, Shaikh Z, Maaliki N, Fahmi K, Been L, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Baber U, Mehran R, Jennings LK, Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Vorapaxar in Prior Myocardial Infarction Patients Treated With Potent Oral P2Y12 Receptor Inhibitors With and Without Aspirin: Results of the VORA-PRATIC Study. J Am Heart Assoc. 2020 Apr 21;9(8):e015865. doi: 10.1161/JAHA.120.015865. Epub 2020 Apr 20.

  PMID: 32306797 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Prasugrel Hydrochloride; vorapaxar; Aspirin; Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Dominick Angiolillo
• Organization: University of Florida

dominick.angiolillo@jax.ufl.edu

9042443378

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida College of Medicine-Jacksonville

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 10, 2015
• Study Start: February 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: January 1, 2020
• Last Updated: September 16, 2020
• Results First Posted: August 25, 2020

Record last verified: 2020-09

Locations

US (1)