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Trial record 3 of 17 for:    cardiac catheterization | Recruiting, Not yet recruiting, Available Studies | NIH, U.S. Fed

Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy

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ClinicalTrials.gov Identifier: NCT02724319
Recruitment Status : Recruiting
First Posted : March 31, 2016
Last Update Posted : April 6, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Human Genome Research Institute (NHGRI)
Information provided by (Responsible Party):
University of Florida

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.

Condition or disease Intervention/treatment
Coronary Artery Disease Device: SpartanRX

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.

Study Type : Observational
Estimated Enrollment : 2500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy for Patients Undergoing Cardiac Catheterization at UF Health Jacksonville
Study Start Date : May 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Group/Cohort Intervention/treatment
Left heart catheterization patients
Patients presenting to the UF Health Jacksonville cardiac catheterization laboratory for left heart catheterization for suspected coronary artery disease and intent to undergo percutaneous coronary intervention will be targeted for enrollment and will be genotyped by SpartanRX
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.




Primary Outcome Measures :
  1. Percent of patients approached who consent to study participation and are genotyped successfully [ Time Frame: 48 hours ]
    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.


Secondary Outcome Measures :
  1. Major adverse cardiac events (MACE) [ Time Frame: 12 months ]
    A composite rate of death, myocardial infarction, stroke, stent thrombosis, and ischemia-driven revascularization


Biospecimen Retention:   Samples With DNA
As part of the study, patients will also be asked to provide consent for the collection and storage of a blood sample to be deidentified and stored in the UF College of Pharmacy Center for Pharmacogenomics Bank (IRB 201500133) for future research to examine additional genetic determinants of effectiveness of antiplatelet therapy as well as asked to consent to the sharing of their de-identified research data through database of Genotypes and Phenotypes (dbGaP) .


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02724319


Contacts
Contact: Dominick J Angiolillo, MD, PhD +1-904-244-3378 dominick.angiolillo@jax.ufl.edu
Contact: Donna Evans, MS +1-904-244-5617 donna.evans@jax.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Jacksonville, Florida, United States, 32209
Contact: Dominick J Angiolillo, MD, PhD       dominick.angiolillo@jax.ufl.edu   
Principal Investigator: Dominick J Angiolillo, MD, PhD         
Sponsors and Collaborators
University of Florida
National Institutes of Health (NIH)
National Human Genome Research Institute (NHGRI)
Investigators
Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida College of Medicine-Jacksonville

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02724319     History of Changes
Other Study ID Numbers: UFJ 2016-14-N
U01HG007269 ( U.S. NIH Grant/Contract )
IRB201703131 ( Other Identifier: Univeristy of Florida )
First Posted: March 31, 2016    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patients will be asked to also have a single blood sample collected which will be stored for future research, and the option to share data to the public NIH database of Genotypes and Phenotypes (dbGaP). dbGaP was developed to archive and distribute the data and results from studies that have investigated the interaction of genotype and phenotype in Humans.

Keywords provided by University of Florida:
percutaneous coronary intervention
clopidogrel
loss-of-function allele

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases