Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy

Coronary Artery Disease Clinical Trial

Official title:

Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy for Patients Undergoing Cardiac Catheterization at UF Health Jacksonville

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02724319
• Other study ID #: IRB201703131
• Secondary ID: U01HG007269IRB20
• Status: Completed
• Start date: May 2016
• Est. completion date: December 31, 2021

Study information

• Verified date: May 2022
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

It is well established that clopidogrel-induced antiplatelet effects is suboptimal in many patients who are thus exposed to an increased risk of adverse cardiovascular events. Studies have shown that genotypes of the cytochrome P450 (CYP) 2C19 enzyme, which is a key determinant of clopidogrel metabolism, contribute to these findings. Prasugrel and ticagrelor are alternative agents whose effectiveness is not dependent on CYP2C19 genotype. A boxed warning on the Food and Drug Administration (FDA)-approved clopidogrel labeling warns of reduced effectiveness in patients with the LOF genotype and recommends alternative therapies in these patients. The availability of an assay recently approved by the FDA, SpartanRX, which provides results within one-hour facilitates performing genetic testing as a clinical test in real-world practice. We therefore propose to 1) examine the feasibility of implementing CYP2C19 genotyping using SpartanRX as standard of care for patients undergoing cardiac catheterization at UF Health Jacksonville providing the opportunity for clinicians to embrace genotype-guided antiplatelet therapy in those who proceed to PCI and 2) determine if CYP2C19 genotype-guided antiplatelet therapy reduces the risk for major adverse cardiovascular outcomes after PCI.

Description:

Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor represents the standard of care treatment for the prevention of major adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). Currently, 3 oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) are available for clinical use. Clopidogrel remains the most broadly used P2Y12 receptor inhibitor. However, it is well established that clopidogrel-induced antiplatelet effects is suboptimal in many patients who are thus exposed to an increased risk of adverse cardiovascular events. Studies have shown that genotypes of the cytochrome P450 (CYP) 2C19 enzyme, which is a key determinant of clopidogrel metabolism, contribute to these findings. In fact, clopidogrel is a prodrug that requires bioactivation by the CYP2C19 enzyme. Approximately 30-40% of individuals have the loss-of-function (LOF) CYP2C19 genotype and cannot sufficiently convert clopidogrel to its active form, thereby gaining little to no benefit from the drug. Prasugrel and ticagrelor are alternative agents whose effectiveness is not dependent on CYP2C19 genotype. A boxed warning on the Food and Drug Administration (FDA)-approved clopidogrel labeling warns of reduced effectiveness in patients with the LOF genotype and recommends alternative therapies in these patients. Guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) specifically recommend prasugrel or ticagrelor over clopidogrel for patients with a LOF CYP2C19 genotype who undergo PCI. In turn, these recommendations have led to the use in clinical practice of genetic testing of CYP2C19 genotypes as an aid to clinicians in determining therapeutic strategies for patients undergoing PCI. However, the uptake of genetic testing in real-world clinical practice has been limited by the availability of assays able to provide genetic results in a timely fashion. The availability of an assay recently approved by the FDA, SpartanRX, which provides results within one-hour facilitates performing genetic testing as a clinical test in real-world practice. We therefore propose to 1) examine the feasibility of implementing CYP2C19 genotyping using SpartanRX as standard of care for patients undergoing cardiac catheterization at UF Health Jacksonville providing the opportunity for clinicians to embrace genotype-guided antiplatelet therapy in those who proceed to PCI and 2) determine if CYP2C19 genotype-guided antiplatelet therapy reduces the risk for major adverse cardiovascular outcomes after PCI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: December 31, 2021
• Est. primary completion date: November 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years

• Undergoing left heart catheterization for signs and symptoms suggestive for CAD

Exclusion Criteria:

• Inability to provide written informed consent.

Related Conditions & MeSH terms

• Coronary Artery Disease

Intervention

Device:
• SpartanRX
A buccal swap genetic sample will be collected from eligible patients who provide written informed consent for CYP2C19 testing. Genotyping will be performed by the SpartanRX system as a clinical test at the UF Health Pathology Laboratory in Jacksonville.

Locations

Country	Name	City	State
United States	University of Florida	Jacksonville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients approached who consent to study participation and are genotyped successfully	Patients undergoing elective procedures will be approached for CYP2C19 genetic testing prior to undergoing left heart catheterization, while patients requiring emergent procedures will be tested prior to hospital discharge.	48 hours
Secondary	Major adverse cardiac events (MACE)	A composite rate of death, myocardial infarction, stroke, stent thrombosis, and ischemia-driven revascularization	12 months