Pharmacogenomics in Stroke: Feasibility of CYP2C19 Testing

NCT06943586 | Recruiting

• 2 other identifiers: IRB-300013920MULTIPI8165
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke; Transient Ischemic Attack (TIA)

Keywords

Personalized medicine; CYP2C19; minor stroke; Transient Ischemic Attack; TIA

Outcome Measures

Primary Outcomes (1)

• Stroke participant feasibility of return of CYP2C19 genetic testing results

  This outcome is to determine the feasibility of receiving CYP2C19 genetic testing results (strata-normal vs. loss-of-function allele) on minor ischemic stroke and high risk TIA inpatients within a 6-hour window to determine drug metabolization for antiplatelet effect to guide standard of care treatment. Inpatients that have been admitted to the hospital, within 66 hours of last known well time, will have buccal swabs collected during hospitalization for the CYP2C19 genetic testing. Results must be received within 6 hours to effectively randomize subjects.

  6 hours from buccal swab collection

Secondary Outcomes (1)

• Recurrent stroke, TIA, major bleeding and Modified Rankin Scale at ~90days

  90 days following stroke

Study Arms (2)

CYP2C19 strata-normal

ACTIVE COMPARATOR

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.

Genetic: CYP2C19 Genotype Guided DAPT (dual antiplatelet therapy)

loss-of-function CYP2C19 allele

ACTIVE COMPARATOR

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.

Genetic: CYP2C19 Genotype Guided DAPT (dual antiplatelet therapy)

Interventions

CYP2C19 Genotype Guided DAPT (dual antiplatelet therapy) GENETIC

CYP2C19 is a gene that encodes an enzyme responsible for metabolizing several medications, including the antiplatelet drugs.

Also known as: genotype guided antiplatelet treatment

CYP2C19 strata-normal; loss-of-function CYP2C19 allele

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18-89 years of age
• admitted to University of Alabama at Birmingham (UAB) main hospital with symptoms or signs of minor ischemic stroke, or high risk TIA
• eligible to receive dual antiplatelet load (presented to the hospital within 66 hours of last known well)

You may not qualify if:

• diagnosis of atrial fibrillation, valvular heart disease, index stroke due to known hypercoagulability (subset of other determined etiology) or large vessel disease (culprit vessel stenosis of ≥50%)
• prescribed anticoagulation prior to stroke
• treated with intravenous thrombolysis
• treated with mechanical thrombectomy
• missing NIH Stroke Scale score

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Related Publications (5)

• Nordeen JD, Patel AV, Darracott RM, Johns GS, Taussky P, Tawk RG, Miller DA, Freeman WD, Hanel RA. Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications. J Vasc Interv Neurol. 2013 Jun;6(1):26-34.

  PMID: 23826440 BACKGROUND

• Meschia JF, Walton RL, Farrugia LP, Ross OA, Elm JJ, Farrant M, Meurer WJ, Lindblad AS, Barsan W, Ching M, Gentile N, Ross M, Nahab F, Easton JD, Kim AS, Zurita KG, Cucchiara B, Johnston SC. Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial. Stroke. 2020 Jul;51(7):2058-2065. doi: 10.1161/STROKEAHA.119.028713. Epub 2020 Jun 17.

  PMID: 32568642 BACKGROUND

• Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC, Li H, Bath PM, Dong Q, Xu A, Jing J, Lin J, Niu S, Wang Y, Zhao X, Li Z, Jiang Y, Li W, Liu L, Xu J, Chang L, Wang L, Zhuang X, Zhao J, Feng Y, Man H, Li G, Wang B; CHANCE-2 Investigators. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. N Engl J Med. 2021 Dec 30;385(27):2520-2530. doi: 10.1056/NEJMoa2111749. Epub 2021 Oct 28.

  PMID: 34708996 BACKGROUND

• Pereira NL, Cresci S, Angiolillo DJ, Batchelor W, Capers Q 4th, Cavallari LH, Leifer D, Luzum JA, Roden DM, Stellos K, Turrise SL, Tuteja S; American Heart Association Professional/Public Education and Publications Committee of the Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Peripheral Vascular Disease; and Stroke Council. CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association. Circulation. 2024 Aug 6;150(6):e129-e150. doi: 10.1161/CIR.0000000000001257. Epub 2024 Jun 20.

  PMID: 38899464 BACKGROUND

• Prevention: Cfdca. Centers for disease control and prevention: Stroke. Accessed May 18, 2023

  BACKGROUND

MeSH Terms

Conditions

Stroke; Ischemic Attack, Transient

Condition Hierarchy (Ancestors)

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

Study Officials

• Ekaterina Bakradze, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ekaterina Bakradze, MD

CONTACT

205-975-8569; ebakradze@uabmc.edu

Nita Limdi, PharmD, PhD

CONTACT

205-934-4385; nlimdi@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants will undergo collection of buccal swabs for CYP2C19 testing and be randomized (depending on CYP2C19 strata- normal vs. loss-of-function (LOF)\* CYP2C19 allele) to their assigned study medications (aspirin and clopidogrel vs aspirin and ticagrelor).

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 24, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)