Genotype-guided P2Y12 inhibitor selection versus standard clopidogrel for symptomatic intracranial atherosclerosis

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy in Symptomatic Intracranial Atherosclerotic Disease: A Pilot Prospective, Randomized, Open-label, Blinded-endpoint (PROBE) Multi- Centre Study

This test will see if using a point-of-care CYP2C19 genetic test to guide whether people who recently had a TIA or ischemic stroke from intracranial atherosclerosis should take ticagrelor plus aspirin instead of standard clopidogrel plus aspirin to lower the chance of another stroke.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (other)
• Locations: 2 sites (Calgary, Alberta and 1 other locations)
• Trial ID: NCT06714526 on ClinicalTrials.gov

What this trial studies

Adults with a recent TIA or ischemic stroke caused by 30–99% intracranial atherosclerotic stenosis are randomized to either genotype-guided antiplatelet selection or conventional clopidogrel therapy. The genotype arm undergoes point-of-care CYP2C19 testing and patients with loss-of-function alleles are given ticagrelor plus aspirin while others receive clopidogrel plus aspirin; the standard arm receives clopidogrel plus aspirin for 90 days. The trial targets enrollment within 30 days of the index event and requires clinical indication for at least three months of dual antiplatelet therapy. The primary aim is to see if genotype-guided selection reduces recurrent ischemic events compared with routine clopidogrel-based therapy.

Who should consider this trial

Good fit: Adults aged 40 or older who had a TIA or ischemic stroke within the past 30 days caused by 30–99% intracranial atherosclerotic stenosis and who can receive dual antiplatelet therapy are ideal candidates.

Not a fit: People with contraindications to dual antiplatelet therapy, those requiring chronic anticoagulation, pregnant women, or those with complete (100%) intracranial occlusion are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, genotype-guided selection could reduce recurrent strokes by identifying patients who will not benefit from clopidogrel and who should receive ticagrelor instead.

How similar studies have performed: Genotype-guided antiplatelet selection has shown benefit in some coronary artery disease studies, but stroke-specific and intracranial atherosclerosis data are limited.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Calgary, Alberta and 1 other locations

• University of Calgary — Calgary, Alberta, Canada (NOT_YET_RECRUITING)
• Dr. Mark I. Boulos - Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Mark I Boulos, MD — Sunnybrook Health Sciences Centre
• Study coordinator: Mark I Boulos, MD

Conditions: Intracranial Atherosclerosis