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

November 17, 2025 updated by: Sunnybrook Health Sciences Centre

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N3M5
        • Recruiting
        • Dr. Mark I. Boulos - Sunnybrook Health Sciences Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Point-of-Care CYP2C19 Testing
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
Genetic testing with the Genomadix cube to determine P2Y12 inhibitor
Drug: ticagrelor + aspirin
If patients are poor or intermediate metabolizers of clopidogrel, they will receive ticagrelor (90 mg PO BID) + aspirin (81 mg PO daily)
Drug: clopidogrel + aspirin
Normal, rapid, and ultra-rapid metabolizers of clopidogrel will receive 75 mg PO daily of clopidogrel and 81 mg PO daily of aspirin.
No Intervention: Standard of Care
Patients will receive standard-of-care ASA + clopidogrel.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Through study completion, an average of 90 days
Rate of study completion
Time Frame: Through study completion, an average of 90 days
The number of patients who complete the entire study protocol
Through study completion, an average of 90 days
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
Through study completion, an average of 90 days
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
Through study completion, an average of 90 days
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
Through study completion, an average of 90 days
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
Through study completion, an average of 90 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound
Time Frame: Day 5 ± 2
Day 5 ± 2
Change in number of ischemic strokes and white matter hyperintensities
Time Frame: Day 0 + 3 and Day 90 ± 14
Day 0 + 3 and Day 90 ± 14
Number of patients with ischemic stroke, myocardial infarction, or death
Time Frame: Day 90 ± 14
Day 90 ± 14
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.
Day 0 and Day 90 ± 14
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.
Day 0 and Day 90 ± 14
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.
Day 0 and Day 90 ± 14
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.
Day 90 ± 14
Change in volume of ischemic strokes and white matter hyperintensities (optional)
Time Frame: Day 0 + 14 and Day 90 ± 14
Day 0 + 14 and Day 90 ± 14
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".
Day 90 ± 14
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).
Day 90 ± 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sunnybrook Health Sciences Centre

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mark I Boulos, MD, Sunnybrook Health Sciences Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 7, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 25, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 28, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 3, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5902

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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