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

NCT06292117 | Recruiting

• 1 other identifier: 230247
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke; CYP2C19 Polymorphism

Keywords

pharmacogenomics; pharmacogenetics; dual antiplatelet therapy; secondary prevention of ischemic stroke

Outcome Measures

Primary Outcomes (2)

• Percentage of patients discharged from University of Virginia (UVA) Health on dual antiplatelet therapy with a diagnosis of AIS/TIA meeting eligibility criteria upon presentation that are successfully genotyped

  At time of participant discharge from hospital; approximately 1-5 days

• Average turnaround time of genotype result from time of collection of blood sample to time result is entered into the electronic health record

  From time of participant blood draw up to 21 days after

Secondary Outcomes (5)

• Number of CYP2C19 LOF carriers for whom a genotype-guided modification to DAPT is made

  Within 30 days of participant index event

• Number needed to genotype (NNG): number of patients who would need to undergo genotyping to have a recommended change in DAPT based on genotype

  Within 30 days of participant index event

• Stroke-free status via the Questionnaire to Verify Stroke-Free Status (QVSFS) of participants at 90 days in participants who received DAPT

  90 days after participant index event

• Major adverse cardiovascular events at 90 days in participants who received DAPT

  90 days after participant index event

• Correlation between P2Y12 reaction units (PRUs) measured via P2Y12 assay and CYP2C19 genotype in patients who received DAPT

  During participant admission, approximately 1-3 days

Other Outcomes (2)

• Acceptability of deferred consent process in participants approached for full informed consent

  At time of 90-day follow-up

• Cost-effectiveness of CYP2C19-guided dual antiplatelet therapy after acute ischemic stroke

  From time of participant blood draw up to 90 days after

Interventions

CYP2C19 Genotype OTHER

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals evaluated in the Emergency Department or admitted inpatient at an academic medical center

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead
• American Heart Association: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples and extracted DNA from each participant who consents to specimen banking will be retained.

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Rachael M Stone, PharmD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Weko, MPH

CONTACT

434-297-6777; crx3qp@uvahealth.org

Rachael M Stone, PharmD

CONTACT

zny6vz@uvahealth.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 25, 2024
• First Posted: March 4, 2024
• Study Start: April 16, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

US (1)