A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:

NCT02065479 | Completed Phase 4 Results DMC

• 2 other identifiers: UFJ 2014-12IRB201702750
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Numerous studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel treated patients and that individuals with reduced response have an increased risk of recurrent ischemic events. There are multiple factors contributing to clopidogrel response variability, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme. In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its active metabolite. Thus, patients carrying LOF alleles have lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition, which translates into an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI). Prasugrel and ticagrelor are novel generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms. However, to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF carriers. The aim of the present study is to compare the PD effects of prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid identification of CYP2C19 genetic status.

Conditions

Coronary Artery Disease

Keywords

Coronary Artery Disease; Percutaneous Coronary Intervention; Genetic Polymorphism; Pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity

  The primary endpoint is P2Y12 reaction unit (PRU) measured by the Verify Now P2Y12 assay 24hours/hospital discharge post randomization to prasugrel vs ticagrelor. PRU is is an arbitrary unit of measure to assess ADP-induced platelet aggregation.

  24 hours post loading dose

Study Arms (2)

Ticagrelor

ACTIVE COMPARATOR

The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.

Drug: Prasugrel

Prasugrel

EXPERIMENTAL

The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.

Drug: Ticagrelor

Interventions

Prasugrel DRUG

Comparison of platelet reactivity between prasugrel and ticagrelor

Also known as: Effient

Ticagrelor

Ticagrelor DRUG

Comparison of platelet reactivity between prasugrel and ticagrelor

Also known as: Brilinta

Prasugrel

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled for left heart catheterization and undergoing PCI
• Age 18-75 years
• On aspirin (81mg) or aspirin (81mg) and clopidogrel (75mg/day)
• Presence of at least one 2C19 LOF allele

You may not qualify if:

• Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel
• Age \>75 years
• Weight \<60kg
• Considered at high risk for bleeding
• History of ischemic or hemorrhagic stroke or transient ischemic attack
• Known severe hepatic dysfunction
• On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran, apixaban, rivaroxaban)
• Use of glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)
• Blood dyscrasia or bleeding diathesis
• Platelet count \<80x106/mL
• Hemoglobin \<10 g/dL.
• Active bleeding or hemodynamic instability
• 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): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• Franchi F, Rollini F, Rivas J, Rivas A, Agarwal M, Briceno M, Wali M, Nawaz A, Silva G, Shaikh Z, Maailiki N, Been L, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-Function Genotypes: Results of a Randomized Pharmacodynamic Study in a Feasibility Investigation of Rapid Genetic Testing. JACC Basic Transl Sci. 2020 Mar 25;5(5):419-428. doi: 10.1016/j.jacbts.2020.02.009. eCollection 2020 May.

  PMID: 32478205 DERIVED

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: Dr. Dominick Angiolillo
• Organization: University of Florida

dominic.angiolillo@jax.ufl.edu

904-244-3378

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida

  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: February 12, 2014
• First Posted: February 19, 2014
• Study Start: March 1, 2014
• Primary Completion: April 22, 2019
• Study Completion: April 22, 2019
• Last Updated: September 16, 2020
• Results First Posted: August 20, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)