Implementation of Onsite Rapid CYP2C19 Assay for Genotype Guided Dual Antiplatelet Therapy After Acute Ischemic Stroke (ORCA-AIS)

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; CYP2C19 Polymorphism
• Intervention / Treatment: Other: CYP2C19 Genotype

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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Andrew Weko, MPH; Phone Number: 434-297-6777; Email: crx3qp@uvahealth.org
• Study Contact Backup: Name: Rachael M Stone, PharmD; Email: zny6vz@uvahealth.org

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Drew Weko, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	P2Y12 assay collected at least 12 hours after loading dose of P2Y12 inhibitor OR after three doses of maintenance dose if did not receive loading dose	During participant admission, approximately 1-3 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability of deferred consent process in participants approached for full informed consent	Structured interview and/or written survey with pre-specified questions	At time of 90-day follow-up
Cost-effectiveness of CYP2C19-guided dual antiplatelet therapy after acute ischemic stroke	Cost-effectiveness analysis reporting incremental cost-effectiveness ratios (ICER)	From time of participant blood draw up to 90 days after

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Rachael M Stone, PharmD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: February 25, 2024
• First Submitted That Met QC Criteria: March 2, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pharmacogenetics; pharmacogenomics; dual antiplatelet therapy; secondary prevention of ischemic stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: 230247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Deidentified data may be made available after reasonable request to the PI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No