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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Florida
Sponsor:
Information provided by (Responsible Party):
Dominick Angiolillo, University of Florida
ClinicalTrials.gov Identifier:
NCT02065479
First received: February 12, 2014
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Drug: Prasugrel
Drug: Ticagrelor
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients With Coronary Artery Disease Undergoing PCI With CYP2C19 Loss-of-function Genotypes: A Feasibility Study With Point-of-care Pharmacodynamic and Genetic Testing

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Platelet reactivity [ Time Frame: 18-24 hours post PCI ] [ Designated as safety issue: No ]
    The primary endpoint is a Platelet reactivity unity (PRU) measured by the Verify Now P2Y12 assay 24hours/hospital discharge post randomization to prasugrel vs ticagrelor


Secondary Outcome Measures:
  • Platelet reactivity [ Time Frame: 30 minutes, 2 hours, 1-4 weeks after PCI ] [ Designated as safety issue: No ]
    Platelet reactivity at various other time points measured using the Verify Now P2Y12 assay.


Estimated Enrollment: 50
Study Start Date: March 2014
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
Drug: Prasugrel
Comparison of platelet reactivity between prasugrel and ticagrelor
Other Name: Effient
Experimental: Prasugrel
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
Drug: Ticagrelor
Comparison of platelet reactivity between prasugrel and ticagrelor
Other Name: Brilinta

Detailed Description:

Clopidogrel is the most broadly utilized platelet P2Y12 receptor inhibitor. However, 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. Among these, genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key contributor to clopidogrel metabolism, have been involved. 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). Because of these findings, drug regulating authorities have provided a boxed warning on the product label of clopidogrel on the potential for reduced efficacy of clopidogrel among CYP2C19 LOF carriers and suggested considering alternative antiplatelet therapies for these individuals. 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. Tailoring antiplatelet therapy according to results of genetic testing has been limited in real world clinical practice because of not having readily accessible results of individual's genetic makeup. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion criteria:

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

    1. Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel
    2. Age >75 years
    3. Weight <60kg
    4. Considered at high risk for bleeding
    5. History of ischemic or hemorrhagic stroke or transient ischemic attack
    6. Known severe hepatic dysfunction
    7. On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran, apixaban, rivaroxaban)
    8. Use of glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)
    9. Blood dyscrasia or bleeding diathesis
    10. Platelet count <80x106/mL
    11. Hemoglobin <10 g/dL.
    12. Active bleeding or hemodynamic instability
    13. Creatinine Clearance <30 mL/minute
    14. Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
    15. 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.
    16. Pregnant females* *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02065479

Contacts
Contact: Dominick J Angiolillo, MD, PhD 904-244-3378 dominick.angiolillo@jax.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Jacksonville, Florida, United States, 32209
Contact: Dominick Angiolillo       dominick.angiolillo@jax.ufl.edu   
Principal Investigator: Dominick J Angiolillo, MD, PhD         
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida
  More Information

No publications provided

Responsible Party: Dominick Angiolillo, Director, Cardiovascular Research, University of Florida
ClinicalTrials.gov Identifier: NCT02065479     History of Changes
Other Study ID Numbers: UFJ 2014-12
Study First Received: February 12, 2014
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Coronary Artery Disease
Percutaneous Coronary Intervention
Genetic Polymorphism
Pharmacodynamic

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Prasugrel
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014