Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy in Symptomatic ICAD

NCT06714526 | Recruiting DMC

• 1 other identifier: 5902
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Stroke is an important cause of death, disability, and memory problems in adults. The build-up of plaque in arteries inside the brain is known as "intracranial atherosclerotic disease" or "ICAD" for short, and can reduce blood flow in the brain. Clopidogrel is a medicine used to prevent strokes because it stops blood from clotting. However, there are some people who do not get as much benefit from Clopidogrel because of differences in their genes; they have a variation in a certain gene and their body is not able to properly process Clopidogrel. Another medication called Ticagrelor can benefit people who have this genetic variation. The study investigators will randomize patients who have had a stroke due to ICAD to receive genetic testing, or standard of care. The standard-of-care group will take Clopidogrel for 90 days. The genetic testing group will complete a genetic test to see if they can properly process Clopidogrel. Depending on the results of the genetic test, patients will either take Clopidogrel or Ticagrelor for 90 days. All patients will have a brain scan at baseline and 90 days to see if they had any new strokes. Patients will also complete tests and questionnaires about function and memory at baseline and 90 days. This study will be one of the first to see if it is feasible and safe to use genetic testing to help choose medications for patients who have had a stroke. This will help the study investigators design a larger study that can test if genetic testing in stroke patients reduces future stroke risk and improves health outcomes.

Conditions

Intracranial Atherosclerosis

Outcome Measures

Primary Outcomes (6)

• Rate of recruitment

  The number of patients who provide informed consent, or are deemed ineligible after screening.

  Through study completion, an average of 90 days

• Rate of study completion

  The number of patients who complete the entire study protocol

  Through study completion, an average of 90 days

• Rate of protocol deviations

  The number of patients who encounter at least one protocol deviation during the study

  Through study completion, an average of 90 days

• Proportion of patients with Symptomatic intracerebral hemorrhage (ICH)

  New symptomatic ICH OR worsening existing ICH with a ≥33% increase in hematoma volume AND NIHSS score increase of ≥4 points AND clinical change is thought to be attributable to ICH

  Through study completion, an average of 90 days

• Proportion of patients with major extracranial bleeding

  Bleeding in a critical area or organ, including intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, intramuscular with compartment syndrome, and/or bleeding causing a drop in hemoglobulin by 20g/L or more

  Through study completion, an average of 90 days

• Proportion of patients with non-bleeding adverse events

  Non-bleeding adverse events related to the study drug including dyspnea, bradyarrhythmia, and/or chest pain

  Through study completion, an average of 90 days

Secondary Outcomes (10)

• Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound

  Day 5 ± 2

• Change in volume of ischemic strokes and white matter hyperintensities (optional)

  Day 0 + 14 and Day 90 ± 14

• Change in number of ischemic strokes and white matter hyperintensities

  Day 0 + 3 and Day 90 ± 14

• Number of patients with ischemic stroke, myocardial infarction, or death

  Day 90 ± 14

• Change in Montreal Cognitive Assessment (MoCA) score from baseline to follow-up

  Day 0 and Day 90 ± 14

Study Arms (2)

Point-of-Care CYP2C19 Testing

EXPERIMENTAL

Patients will undergo point-of-care CYP2C19 testing with the Research Use Only (RUO) Genomadix Cube to inform the choice of P2Y12 inhibitor (i.e. clopidogrel vs ticagrelor).

Genetic: Point-of-Care CYP2C19 Testing; Drug: ticagrelor + aspirin; Drug: clopidogrel + aspirin

Standard of Care

NO INTERVENTION

Patients will receive standard-of-care ASA + clopidogrel.

Interventions

Point-of-Care CYP2C19 Testing GENETIC

Genetic testing with the Genomadix cube to determine P2Y12 inhibitor

Point-of-Care CYP2C19 Testing

ticagrelor + aspirin DRUG

If patients are poor or intermediate metabolizers of clopidogrel, they will receive ticagrelor (90 mg PO BID) + aspirin (81 mg PO daily)

Point-of-Care CYP2C19 Testing

clopidogrel + aspirin DRUG

Normal, rapid, and ultra-rapid metabolizers of clopidogrel will receive 75 mg PO daily of clopidogrel and 81 mg PO daily of aspirin.

Point-of-Care CYP2C19 Testing

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 40 years old, male and female.
• TIA or ischemic stroke secondary to symptomatic atherosclerotic stenosis of 30- 99% involving the intracranial ICA or MCA or posterior circulation arteries as evidenced by CT or MR angiography.
• Index TIA or ischemic stroke event occurred within past 30 days.
• Clinical indication for DAPT for at least 3 months.

You may not qualify if:

• Any contraindication to DAPT.
• Any contraindication to use of clopidogrel (Plavix) or ticagrelor (Brilinta), such as pregnancy. A pregnancy test will be performed on all women of child-bearing age prior to enrollment in the study.
• Indication for chronic anticoagulation based on guideline recommendations or investigator's judgment (e.g., atrial fibrillation, mechanical heart valve, intracardiac clot, dilated cardiomyopathy, ejection fraction \<30%, etc.).
• Intracranial arterial occlusion (i.e. 100% stenosis) responsible for the acute brain ischemia.
• Intracranial arterial stenosis secondary to causes other than atherosclerosis.
• Extracranial carotid disease with a plan for carotid revascularization.
• Intraluminal thrombus.
• Unstable subdural hematoma within 12 months of randomization not amenable to embolization.
• Previous spontaneous hemorrhagic stroke.
• Traumatic brain hemorrhage within 1 month of randomization.
• Living in a nursing home or requiring daily nursing care or assistance with activities of daily living.
• Intracranial tumor (except meningioma) or any intracranial vascular malformation.
• Life expectancy less than 6 months.
• Enrolment in another study that would conflict with the current study.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (2)

University of Calgary

Calgary, Alberta, Canada

NOT YET RECRUITING

Dr. Mark I. Boulos - Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

MeSH Terms

Conditions

Intracranial Arteriosclerosis

Interventions

Ticagrelor; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mark I Boulos, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark I Boulos, MD

CONTACT

416-480-4473; mark.boulos@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: December 3, 2024
• Study Start: October 7, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)