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NCT Number: NCT06714526

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

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.

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Key information

Conditions

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

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Calgary, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Point-of-Care CYP2C19 Testing

Genetic

Genetic testing with the Genomadix cube to determine P2Y12 inhibitor

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)

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.

Primary outcomes

  1. Rate of recruitment

    Time frame: Through study completion, an average of 90 days

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

  2. Rate of study completion

    Time frame: Through study completion, an average of 90 days

    The number of patients who complete the entire study protocol

  3. Rate of protocol deviations

    Time frame: Through study completion, an average of 90 days

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

  4. Proportion of patients with Symptomatic intracerebral hemorrhage (ICH)

    Time frame: Through study completion, an average of 90 days

    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

  5. Proportion of patients with major extracranial bleeding

    Time frame: Through study completion, an average of 90 days

    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

  6. Proportion of patients with non-bleeding adverse events

    Time frame: Through study completion, an average of 90 days

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

Secondary outcomes

  1. Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound

    Time frame: Day 5 ± 2

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

    Time frame: Day 0 + 14 and Day 90 ± 14

  3. Change in number of ischemic strokes and white matter hyperintensities

    Time frame: Day 0 + 3 and Day 90 ± 14

  4. Number of patients with ischemic stroke, myocardial infarction, or death

    Time frame: Day 90 ± 14

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

    Time frame: Day 0 and Day 90 ± 14

    To MoCA is a validated cognitive screening tool. Possible scores range from 0 (worst score) to 31 (best score). Change = Follow-up - baseline.

  6. Change in NIH Stroke Scale (NIHSS) score from baseline to follow-up

    Time frame: Day 0 and Day 90 ± 14

    This scale is a 15 item tool used to quantify stroke severity. Scores range from 0 (no stroke) to 42 (most severe stroke). Change = Follow-up - baseline.

  7. Change or shift in modified Rankin Scale (mRS) score from baseline to follow-up

    Time frame: Day 0 and Day 90 ± 14

    The MRS is a single item rating of stroke outcomes. Scores range from 0 (no symptoms) to 6 (death). Change = Follow-up - baseline.

  8. Self-reported Quality of Life as assessed by the EQ-5D-5L

    Time frame: Day 90 ± 14

    The EQ-5D-5L questionnaire has 5 dimensions: Mobility, Self-Care, Usual Activity, Pain/Discomfort, Anxiety/Depression, with each dimension rated on a level from 1-5 where higher scores indicate more severe problems.

  9. Self-reported Dementia Screening assessed by the AD8 Dementia Screening Interview

    Time frame: Day 90 ± 14

    The AD8 Dementia Screening Interview has 8 questions that ask if there has been a change in the last several years caused by cognitive (thinking and memory) problems. The score is the sum of all items marked "Yes, A change".

  10. Self-reported functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living Scale

    Time frame: Day 90 ± 14

    The Lawton-Brody Instrumental Activities of Daily Living Scale has 8 categories where participants can rate their functional level. Scores range from 0 (low function, dependent) to 8 (high function, independent).

Study contacts

Contact information is provided by the study sponsor or research team.

Mark I Boulos, MD

CONTACT

[email protected]

416-480-4473

Sponsors and collaborators

Lead sponsor

Sunnybrook Health Sciences Centre

Other

Registry information

Official study title

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

Acronym: NUANCE-ICAD

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Dec 3, 2024
Registry last updated
Nov 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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