Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-function: a Validation Study

NCT03489863 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB201703338 -A
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Polymorphisms of the cytochrome P450 (CYP) 2C19 enzyme has been consistently shown to modulate clopidogrel response. Accordingly, the Food and Drug Administration (FDA) has issued a warning on the potential for reduced efficacy of clopidogrel among carriers of loss-of-function alleles (LOF) for CYP2C19 and suggest considering alternative antiplatelet therapies for these individuals. The pharmacodynamic (PD) effects of prasugrel and ticagrelor are not affected by CYP2C19 genetic polymorphisms. However, to date there are no head-to-head PD comparisons between these agents among patients with different CYP2C19 genetic polymorphisms, which is currently under investigation in CAD patients undergoing PCI at UF Health-Jacksonville (UFJ 2014-12, NCT 02065479). In order to rule out play of chance findings, pharmacogenetic investigations require external validation cohorts to support the study findings. Therefore, the present randomized study is designed to serve as an external validation cohort conducted in patients with established CAD not undergoing PCI testing the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 LOF allele carriers.

Conditions

Coronary Artery Disease

Keywords

clopidogrel; prasugrel; ticagrelor

Outcome Measures

Primary Outcomes (1)

• P2Y12 Reaction Unit (PRU)

  Platelet reactivity measured by VerifyNow and reported as PRU

  at 24 hours post loading dose

Study Arms (2)

Prasugrel

ACTIVE COMPARATOR

Patients will be randomly (1:1) assigned to receive FDA approved doses of either prasugrel (60 mg loading dose - 10 mg/day maintenance dose) or ticagrelor (180 mg loading dose - 90 mg b.i.d maintenance dose).

Drug: Prasugrel

Ticagrelor

ACTIVE COMPARATOR

Patients will be randomly (1:1) assigned to receive FDA approved doses of either prasugrel (60 mg loading dose - 10 mg/day maintenance dose) or ticagrelor (180 mg loading dose - 90 mg b.i.d maintenance dose).

Drug: Ticagrelor

Interventions

Prasugrel DRUG

Maintenance dose will be maintained for 10±3 days.

Also known as: Effient

Prasugrel

Ticagrelor DRUG

Maintenance dose will be maintained for 10±3 days.

Also known as: Brilinta

Ticagrelor

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 CAD \[defined as the presence of at least a 50% stenosis in a major epicardial vessel or major branch, or any prior coronary revascularization (PCI or coronary bypass graft surgery)\] on treatment with either aspirin (81mg/day) or aspirin and clopidogrel (75m/day) for at least 30 days as per standard of care
• Participated in UFJ 2016-14 study with genetic buccal swab test and have at least one CYP 2C19 LOF allele (CYP2C19\*2 and CYP2C19\*3)
• Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

You may not qualify if:

• Known allergies to prasugrel or ticagrelor
• Weight \<60kg
• Considered at high risk for bleeding
• Currently active bleeding
• History of ischemic or hemorrhagic stroke or transient ischemic attack, or intracranial hemorrhage
• Known severe hepatic dysfunction
• On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran, apixaban, rivaroxaban)
• Platelet count \<80x106/mL
• Hemoglobin \<10 g/dL.
• Creatinine Clearance \<30 mL/minute
• Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
• Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with ticagrelor): CYP3A Inhibitors (ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin ) and CYP3A Inducers (rifampin, phenytoin, carbamazepine, and phenobarbital)
• Pregnant or breastfeeding females

Sponsors & Collaborators

• University of Florida: lead
• Scott R. MacKenzie Foundation: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

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

dominick.angiolillo@jax.ufl.edu

9042443378

Study Officials

• Dominick J Angiolillo, MD,PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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

Model Details: Prospective randomized

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: April 6, 2018
• Study Start: May 30, 2018
• Primary Completion: March 20, 2019
• Study Completion: March 20, 2019
• Last Updated: September 16, 2020
• Results First Posted: August 24, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)