Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy

NCT02724319 | Completed

• 2 other identifiers: IRB201703131U01HG007269
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

percutaneous coronary intervention; clopidogrel; loss-of-function allele

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Major adverse cardiac events (MACE)

  12 months

Study Arms (1)

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

Interventions

SpartanRX DEVICE

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.

Left heart catheterization patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Inability to provide written informed consent.

Sponsors & Collaborators

• University of Florida: lead
• National Institutes of Health (NIH): collaborator
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• 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.

  PMID: 29642909 DERIVED

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) .

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida College of Medicine-Jacksonville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 31, 2016
• Study Start: May 1, 2016
• Primary Completion: November 20, 2020
• Study Completion: December 31, 2021
• Last Updated: June 2, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)