Genetic Testing for Stroke

Overseen By Nita Limdi, PharmD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Anticoagulants

Disqualifiers: Atrial fibrillation, Valvular heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 21 days

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether genetic testing can help doctors make better medication choices for individuals who have experienced a minor stroke or a high-risk transient ischemic attack (TIA), similar to a mini-stroke. The study examines how different genetic profiles affect responses to common stroke medications, specifically guiding the use of clopidogrel or ticagrelor with aspirin. This approach is known as CYP2C19 Genotype Guided DAPT (dual antiplatelet therapy). Participants will be divided into groups based on their genetic test results to determine which medication combination works best. This trial may suit those who have recently experienced a minor stroke or a high-risk TIA and are admitted to the University of Alabama at Birmingham hospital within 66 hours of the event. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could personalize stroke treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that genetic testing for stroke is safe?

Previous studies using the CYP2C19 genotype to guide dual antiplatelet therapy (DAPT) have shown positive results. This method helps select the right medication based on genetic testing, predicting patient responses to common medications like clopidogrel and ticagrelor, which prevent blood clots.

Research indicates that this approach can reduce the risk of heart problems, such as strokes, for some individuals. Specifically, those with a "loss-of-function" genetic variation in CYP2C19 might benefit from switching to ticagrelor instead of remaining on clopidogrel. This change may lower the chance of another stroke without increasing major bleeding risks.

Safety data from these studies suggest that a genotype-guided method is generally well-tolerated. Although direct evidence of significant improvement in clinical outcomes is lacking, this approach aids in making more informed medication choices, offering promise for personalized treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a personalized approach to stroke treatment by using genetic testing. Unlike traditional treatments, such as standard dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, this trial utilizes the CYP2C19 genotype to guide medication choice between clopidogrel and ticagrelor. This is important because some people have a genetic variant that makes clopidogrel less effective. By tailoring the treatment based on genetic information, there is potential to improve outcomes for stroke patients by ensuring they receive the most effective medication for their genetic makeup.

What evidence suggests that CYP2C19 genotype guided DAPT could be effective for stroke or TIA patients?

Research has shown that using genetic testing to guide antiplatelet therapy can improve outcomes for stroke patients. In this trial, participants will undergo genetic testing to determine their CYP2C19 genotype, which affects how well the stroke medication clopidogrel works in the body. Based on the results, participants will receive either aspirin and clopidogrel or aspirin and ticagrelor. Studies have found that patients with certain genetic profiles who switched from clopidogrel to other medications, like ticagrelor, experienced better results, with a lower risk of another stroke or other heart-related issues. This suggests that customizing treatment based on genetic testing may lead to more effective stroke care. ^{1 2 3 4 5}

Who Is on the Research Team?

Ekaterina Bakradze, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for patients aged 18-89 who have had a minor ischemic stroke or high-risk TIA and are admitted to UAB hospital within 66 hours of symptoms. They must be eligible for dual antiplatelet therapy but not have atrial fibrillation, certain heart diseases, specific clotting disorders, prior anticoagulation treatment, or received mechanical thrombectomy or intravenous thrombolysis.

Inclusion Criteria

I arrived at the hospital within 66 hours since I last felt well and can take dual antiplatelet medication.

I was admitted to UAB for a minor stroke or high risk TIA.

Exclusion Criteria

Missing NIH Stroke Scale score

I have been diagnosed with a heart rhythm problem, heart valve disease, or had a stroke due to blood clot issues or significant artery narrowing.

I have undergone a procedure to remove a blood clot.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genetic Testing and Randomization

Participants undergo buccal swab for CYP2C19 genetic testing to determine potential medication response and are randomized to treatment groups

6 hours

1 visit (in-person)

Treatment

Participants receive aspirin and either clopidogrel or ticagrelor based on genetic testing results for 21 days

21 days

Follow-up

Participants are monitored for recurrent stroke, TIA, major bleeding, and functional recovery using the Modified Rankin Scale

90 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CYP2C19 Genotype Guided DAPT

Trial Overview The study tests if genetic testing (CYP2C19) can help doctors decide on the best medication during hospital stays for stroke or TIA patients. It aims to see if this personalized approach using dual antiplatelet therapy is feasible and effective in improving outcomes.

How Is the Trial Designed?

Group I: loss-of-function CYP2C19 allele Active Control 1 Intervention

Participants undergo buccal swab for genetic testing to determine potential medication response to standard of care (SOC) medications. Upon result, participants are randomized (1:1) to aspirin and clopidogrel vs aspirin and ticagrelor (all SOC for this stroke population). Doses are aspirin either 81mg or loading dose 325mg, clopidogrel either 75mg or loading dose 300mg, ticagrelor either 90mg or loading dose 180mg. Loading doses are given once for aspirin, clopidogrel or ticagrelor; aspirin 81mg is taken once a day for the duration of the study; clopidogrel 75mg is once a day for 21 days only, ticagrelor 90mg is twice daily for 21 days. Participants will only receive loading dose of aspirin if not already taken at home. CYP2C19 results only affect decision regarding clopidogrel and ticagrelor but not aspirin. Aspirin is not affected by CYP2C19 mutation and will be given immediately without waiting for CYP2C19 results.

Group II: CYP2C19 strata-normal Active Control 1 Intervention

Participants undergo buccal swab for genetic testing to determine potential medication response to standard of care (SOC) medications. Upon result, participants are randomized (1:1) to aspirin and clopidogrel vs aspirin and ticagrelor (all SOC for this stroke population). Doses are aspirin either 81mg or loading dose 325mg, clopidogrel either 75mg or loading dose 300mg, ticagrelor either 90mg or loading dose 180mg. Loading doses are given once for aspirin, clopidogrel or ticagrelor; aspirin 81mg is taken once a day for the duration of the study; clopidogrel 75mg is once a day for 21 days only, ticagrelor 90mg is twice daily for 21 days. Participants will only receive loading dose of aspirin if not already taken at home. CYP2C19 results only affect decision regarding clopidogrel and ticagrelor but not aspirin. Aspirin is not affected by CYP2C19 mutation and will be given immediately without waiting for CYP2C19 results.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7419635/

Clinical Utility of CYP2C19 Genotype-Guided Antiplatelet ... Accumulating data demonstrate that CYP2C19 genotype is associated with outcomes in clopidogrel-treated patients following stroke and neurointerventional ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.121.024159

CYP2C19 Genotype‐Guided Antiplatelet Therapy After ... Real‐world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those ...

3. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.70131

CYP2C19 Genotype‐Guided Antiplatelet Therapy and Clinical ... There is no direct evidence that using a CYP2C19 genotype-guided antiplatelet therapy approach improves clinical outcomes in the setting of neurointerventional ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06665919

NCT06665919 | The Study of CYP2C19 Genotype-Guided ... The study aimed to learn the comparative benefits of CYP2C19 genotype-guided versus conventional clopidogrel treatment selection applied in real clinical ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586825007180

Dual antiplatelet therapy guided by CYP2C19 ... The primary efficacy endpoint remained 90-day ischemic stroke; the primary safety endpoint was moderate-to-severe bleeding within 90 days. Results. Of 1,270 ...