Implementation of Onsite Rapid CYP2C19 Assay for Genotype Guided Dual Antiplatelet Therapy After Acute Ischemic Stroke

NCT ID: NCT06292117

Last Updated: 2024-05-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 350 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-16
• Study Completion Date: 2026-06-30

Brief Summary

The goal of this observational study is to use a genetic test to help doctors prescribe the most effective medications after a patient has a stroke. One type of stroke is caused by a blood clot in brain vessels. After a patient has this kind of stroke, they are often given a combination of two blood thinners to prevent it from happening again. One of these blood thinners, called clopidogrel, is less effective in some people due to differences in their DNA. Clopidogrel needs to be activated by a specific enzyme in the body known as CYP2C19. This enzyme does not work as well if there are variations in the section of DNA that tells the body how to make CYP2C19. It can be predicted who has less CYP2C19 enzyme activity with a genetic test. If these patients are given a different blood thinner, it can reduce their risk of another stroke compared to if they are given clopidogrel.

The main questions this study aims to answer are:

• What are the best strategies to implement this genetic test in the hospital?
• Does implementation of this genetic test change providers' decisions on which medication to prescribe after a participant has a stroke?

Participants in this study will have a genetic test done onsite looking for variations in the section of DNA that tells the body how to make CYP2C19. This genetic test will only look for 11 known variations; the genome will not be sequenced. The investigators will alert the doctor of the patient's test results so they can prescribe the appropriate blood thinner. Through this, the investigators will learn the best practices for successful implementation of this genetic test.

Detailed Description

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is the standard of care (SOC) for secondary prevention of non-cardioembolic minor acute ischemic stroke (AIS) and high-risk transient ischemic attack (TIA); however, clopidogrel has limited effectiveness in CYP2C19 loss-of-function (LOF) allele carriers. Recent studies have demonstrated the superiority of ticagrelor over clopidogrel in CYP2C19 LOF allele carriers, especially when started within 24 hours of presentation. However, despite evidence of improved efficacy and advances in rapid genotyping technology, clinical care has been slow to adopt this form of precision medicine. To address this gap, an implementation study will be conducted in adult patients with cerebrovascular disease to determine the feasibility and acceptability of rapid CYP2C19 genotyping in an acute inpatient setting and to analyze the impact of this clinical implementation on DAPT prescribing patterns. To accomplish these aims, patients undergoing evaluation for AIS/TIA in the Emergency Department will be consented for in-house rapid quantitative polymerase chain reaction (qPCR) genotyping of CYP2C19. Genotype results will be recorded in the electronic health record and active clinical decision support alerts will be built to inform prescribers of any recommended DAPT changes.

Conditions

Ischemic Stroke; CYP2C19 Polymorphism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

CYP2C19 Genotype

qPCR-based genotyping assay interrogating all Association for Molecular Pathology (AMP) recommended Tier 1 and Tier 2 single nucleotide polymorphisms (SNPs) for CYP2C19 (\*2, \*3, \*4, \*5, \*6, \*7, \*8, \*9, \*10, \*17, \*35)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Men and women at least 18 years of age
• Presenting with symptoms of acute ischemic stroke or transient ischemic attack and without contraindications to dual antiplatelet therapy at time of clinical research coordinator screening
• Presenting within 24 of symptom onset; or, within 24-96 hours of symptom onset IF planned to receive or already on dual antiplatelet therapy

Exclusion Criteria

• Receiving therapeutic anticoagulation or clear indication for initiation of anticoagulation after event (e.g., known atrial fibrillation)
• History of allogeneic bone marrow transplant
• History of liver transplant
• Subject who is unable to consent and does not have a surrogate available to consent on their behalf

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Rachael Stone

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rachael M Stone, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Andrew Weko, MPH

Role: CONTACT

crx3qp@uvahealth.org

434-297-6777

Rachael M Stone, PharmD

Role: CONTACT

zny6vz@uvahealth.org

Facility Contacts

Drew Weko, MPH

Role: primary

Other Identifiers

230247

Identifier Type: -

Identifier Source: org_study_id