Clinical trial NCT06292117: Implementation of Onsite Rapid CYP2C19 Assay for Genotype Guided Dual Antiplatelet Therapy After Acute Ischemic Stroke
Official title: Implementation of Onsite Rapid CYP2C19 Assay for Genotype Guided Dual Antiplatelet Therapy After Acute Ischemic Stroke
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
CYP2C19 Polymorphism
Keywords: pharmacogenomics
pharmacogenetics
dual antiplatelet therapy
secondary prevention of ischemic stroke
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2024-03-04
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals evaluated in the Emergency Department or admitted inpatient at an academic medical center

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.

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

Primary outcomes:
measure: 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
timeFrame: At time of participant discharge from hospital; approximately 1-5 days
measure: Average turnaround time of genotype result from time of collection of blood sample to time result is entered into the electronic health record
timeFrame: From time of participant blood draw up to 21 days after
Secondary outcomes:
measure: Number of CYP2C19 LOF carriers for whom a genotype-guided modification to DAPT is made
timeFrame: Within 30 days of participant index event
measure: Number needed to genotype (NNG): number of patients who would need to undergo genotyping to have a recommended change in DAPT based on genotype
timeFrame: Within 30 days of participant index event
measure: Stroke-free status via the Questionnaire to Verify Stroke-Free Status (QVSFS) of participants at 90 days in participants who received DAPT
timeFrame: 90 days after participant index event
measure: Major adverse cardiovascular events at 90 days in participants who received DAPT
timeFrame: 90 days after participant index event
measure: Correlation between P2Y12 reaction units (PRUs) measured via P2Y12 assay and CYP2C19 genotype in patients who received DAPT
timeFrame: During participant admission, approximately 1-3 days
Other outcomes:
measure: Acceptability of deferred consent process in participants approached for full informed consent
timeFrame: At time of 90-day follow-up
measure: Cost-effectiveness of CYP2C19-guided dual antiplatelet therapy after acute ischemic stroke
timeFrame: From time of participant blood draw up to 90 days after
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Rachael M Stone, PharmD
role: PRINCIPAL_INVESTIGATOR
References: