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

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to explore whether genetic testing can offer a personalized and timely approach to assist physicians in making more informed medication decisions for stroke or high-risk transient ischemic attack (TIA) patients during their hospital stay.

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 data supports the effectiveness of the treatment CYP2C19 Genotype Guided DAPT for stroke?

Research suggests that understanding a person's CYP2C19 genetic makeup can help tailor antiplatelet therapy, which may improve outcomes for stroke patients. This approach has been shown to be useful in personalizing treatment to prevent further strokes. ^{1 2 3 4 5}

Is CYP2C19 genotype-guided therapy safe for humans?

Research on CYP2C19 genotype-guided therapy, particularly with clopidogrel-based antiplatelet treatment, suggests that genetic factors can influence drug response and safety. However, the safety data is limited and varies among different populations, indicating a need for more studies to fully understand the safety profile. ^{1 2 5 6 7}

How does the CYP2C19 Genotype Guided DAPT treatment for stroke differ from other treatments?

This treatment is unique because it uses genetic testing to guide the choice of antiplatelet drugs, which can help prevent strokes by considering individual genetic differences that affect drug metabolism. This personalized approach aims to improve treatment effectiveness and reduce the risk of adverse effects compared to standard treatments that do not consider genetic factors. ^{1 2 4 5 8}

Research Team

Ekaterina Bakradze, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

The secondary prevention of stroke according to cytochrome P450 2C19 genotype in patients with acute large-artery atherosclerosis stroke. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Does CYP2C19 polymorphisms affect neurological deterioration in stroke/TIA patients?: A systematic review and meta-analysis of prospective cohort studies. [2023]

4. China pubmed.ncbi.nlm.nih.gov

[Correlation between CYP2C19 Gene Polymorphism and Elderly Cerebral Infarction]. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of a rapid point-of-care and two laboratory-based CYP2C19*2 genotyping assays for personalisation of antiplatelet therapy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Genetic signatures in the treatment of stroke. [2019]

8. China pubmed.ncbi.nlm.nih.gov

[Analysis of the association of CYP450 gene polymorphisms with ischemic stroke]. [2023]