A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:
Primary Purpose
Coronary Artery Disease
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Prasugrel
Ticagrelor
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Artery Disease focused on measuring Coronary Artery Disease, Percutaneous Coronary Intervention, Genetic Polymorphism, Pharmacodynamic
Eligibility Criteria
Inclusion criteria:
- 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
Exclusion criteria:
- 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.
- Pregnant females* *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
Sites / Locations
- University of Florida
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Ticagrelor
Prasugrel
Arm Description
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02065479
First Posted
February 12, 2014
Last Updated
August 27, 2020
Sponsor
University of Florida
1. Study Identification
Unique Protocol Identification Number
NCT02065479
Brief Title
A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
April 22, 2019 (Actual)
Study Completion Date
April 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
Coronary Artery Disease, Percutaneous Coronary Intervention, Genetic Polymorphism, Pharmacodynamic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ticagrelor
Arm Type
Active Comparator
Arm Description
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
Arm Title
Prasugrel
Arm Type
Experimental
Arm Description
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
Intervention Type
Drug
Intervention Name(s)
Prasugrel
Other Intervention Name(s)
Effient
Intervention Description
Comparison of platelet reactivity between prasugrel and ticagrelor
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Other Intervention Name(s)
Brilinta
Intervention Description
Comparison of platelet reactivity between prasugrel and ticagrelor
Primary Outcome Measure Information:
Title
Platelet Reactivity
Description
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.
Time Frame
24 hours post loading dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
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
Exclusion criteria:
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.
Pregnant females* *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominick J Angiolillo, MD, PhD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32478205
Citation
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.
Results Reference
derived
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