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

NCT02548650 | Completed Phase 4 Results FDA Drug

• 1 other identifier: IIS 53377
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myocardial Infarction; Diabetes Mellitus; Peripheral Arterial Disease

Keywords

myocardial infarction; diabetes mellitus; vorapaxar; peripheral arterial disease

Outcome Measures

Primary Outcomes (1)

• Maximal Platelet Aggregation in DM

  Comparison of maximal platelet aggregation (%) measured by light transmittance aggregometry between between triple (vorapaxar plus DAPT) and dual (vorapaxar plus clopidogrel) therapy in diabetic patients

  30 days

Secondary Outcomes (1)

• Maximal Platelet Aggregation in Non-DM

  30 days

Study Arms (2)

Patients with diabetes

EXPERIMENTAL

Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.

Drug: Vorapaxar; Drug: Clopidogrel; Drug: Aspirin

Patients without diabetes

ACTIVE COMPARATOR

Triple therapy (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days.

Drug: Vorapaxar; Drug: Clopidogrel; Drug: Aspirin

Interventions

Vorapaxar DRUG

Triple therapy with DAPT plus vorapaxar (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days

Also known as: Zontivity

Patients with diabetes; Patients without diabetes

Clopidogrel DRUG

Triple therapy with DAPT plus vorapaxar (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days

Also known as: Plavix

Patients with diabetes; Patients without diabetes

Aspirin DRUG

Triple therapy with DAPT plus vorapaxar(vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days

Also known as: ASA

Patients with diabetes; Patients without diabetes

Eligibility Criteria

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

You may qualify if:

• Patients with a prior MI between 2 weeks and 24 months or with PAD.
• On DAPT with low-dose aspirin (81mg od) and clopidogrel (75mg od) as per standard-of-care for at least 14 days.
• Age ≥ 18 years old.

You may not qualify if:

• History of acute coronary syndrome in the previous 2 weeks.
• 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.
• 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).
• On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban).
• On treatment with any antiplatelet agent other than aspirin and clopidogrel 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, Kairouz V, Rivas Rios J, Rivas A, Agarwal M, Briceno M, Wali M, Nawaz A, Silva G, Shaikh Z, Maaliki N, Been L, Piraino J, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Jennings LK, Bass TA, Angiolillo DJ. Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study. JACC Basic Transl Sci. 2019 Sep 1;4(7):763-775. doi: 10.1016/j.jacbts.2019.07.011. eCollection 2019 Nov.

  PMID: 31998847 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Diabetes Mellitus; Peripheral Arterial Disease

Interventions

vorapaxar; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dominick J Angiolillo
• Organization: University of Florida College of Medicine - Jacksonville

dominick.angiolillo@jax.ufl.edu

9042443933

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida College of Medicine-Jacksonville

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON 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 14, 2015
• Study Start: March 25, 2016
• Primary Completion: December 1, 2018
• Study Completion: February 14, 2019
• Last Updated: February 12, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)