Clinical trial NCT02724319: Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy
Official title: Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy for Patients Undergoing Cardiac Catheterization at UF Health Jacksonville
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Keywords: percutaneous coronary intervention
clopidogrel
loss-of-function allele
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Human Genome Research Institute (NHGRI)
First posted: 2016-03-31
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients presenting to the UF Health Jacksonville cardiac catheterization laboratory for left heart catheterization for suspected coronary artery disease (CAD) and intent to undergo PCI will be targeted for enrollment.

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Undergoing left heart catheterization for signs and symptoms suggestive for CAD

Exclusion Criteria:

* Inability to provide written informed consent.

Primary outcomes:
measure: Percent of patients approached who consent to study participation and are genotyped successfully
timeFrame: 48 hours
Secondary outcomes:
measure: Major adverse cardiac events (MACE)
timeFrame: 12 months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida College of Medicine-Jacksonville
name: Dominick J Angiolillo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cavallari LH, Franchi F, Rollini F, Been L, Rivas A, Agarwal M, Smith DM, Newsom K, Gong Y, Elsey AR, Starostik P, Johnson JA, Angiolillo DJ. Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention. J Transl Med. 2018 Apr 11;16(1):92. doi: 10.1186/s12967-018-1469-8.