Genetic Testing for Stroke Treatment

(NUANCE-ICAD Trial)

Recruiting at 1 trial location

Overseen By Mark I Boulos, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: DAPT

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Atrial fibrillation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 180

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether genetic testing can guide stroke treatment for better results. It focuses on individuals who have experienced a stroke due to plaque build-up in brain arteries, known as intracranial atherosclerotic disease. Participants will either receive the usual care with the drug Clopidogrel or undergo genetic testing to determine whether they should take Clopidogrel or an alternative, Ticagrelor. Those who have had a stroke or mini-stroke in the last 30 days due to brain artery narrowing might be suitable candidates. The trial aims to determine if genetic testing can reduce future stroke risks and improve health outcomes. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could personalize stroke treatment and enhance patient outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have any contraindications (reasons not to use) to the study medications, Clopidogrel or Ticagrelor, and you cannot be on chronic anticoagulation therapy.

What prior data suggests that genetic testing for stroke treatment is safe?

Research has shown that both Clopidogrel and Ticagrelor, the drugs under study, have been safely used in stroke patients. Clopidogrel, often taken with aspirin to prevent strokes, has proven effective, though it can slightly increase the risk of bleeding. Studies indicate that this combination can lower the chance of another stroke, especially soon after a mild one.

Ticagrelor reduces the risk of stroke in individuals who have experienced a minor stroke or a temporary blockage in blood flow to the brain. Some studies found that Ticagrelor lowers the risk of stroke or death compared to other treatments, but it may also carry a higher risk of bleeding.

Both medications are generally well-tolerated, but their effects can vary based on genetic factors. This study investigates whether genetic testing can help select the more effective medication for each person, aiming to improve outcomes by tailoring treatment to individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores using point-of-care genetic testing to tailor stroke treatment. Unlike the standard approach, which typically involves a fixed regimen of aspirin and clopidogrel, this method uses the Genomadix Cube to determine a patient's CYP2C19 gene status. This personalized approach helps decide whether clopidogrel or ticagrelor is more effective for the individual, potentially enhancing treatment success and reducing complications. By focusing on genetic differences, this trial aims to optimize stroke care and improve outcomes.

What evidence suggests that genetic testing could be effective for stroke treatment?

Research has shown that taking Clopidogrel with aspirin can reduce the risk of another stroke in people who have experienced a mild stroke or a temporary blockage of blood flow to the brain. Studies indicate that this combination is more effective than aspirin alone in preventing new strokes within 90 days. However, genetic differences in some individuals make it difficult for their bodies to process Clopidogrel effectively.

In this trial, participants will undergo point-of-care CYP2C19 testing to determine the most suitable treatment. For those who do not respond well to Clopidogrel, Ticagrelor might be a better option. When combined with aspirin, Ticagrelor lowered the risk of a stroke caused by blocked blood flow to the brain by 20%. This suggests that Ticagrelor could be effective for those who do not respond well to Clopidogrel. ^{2 3 4 6 7}

Who Is on the Research Team?

Mark I Boulos, MD, MSc

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for adults who've had a stroke due to plaque build-up in brain arteries (ICAD). Participants must be willing to undergo genetic testing or take standard medication, Clopidogrel, for 90 days. Specific eligibility criteria are not provided but typically include factors like age, medical history, and the ability to comply with study requirements.

Inclusion Criteria

I need dual antiplatelet therapy for at least 3 months.

I had a stroke or mini-stroke in the last 30 days.

I am 40 years old or older.

Exclusion Criteria

I cannot take clopidogrel or ticagrelor due to reasons like pregnancy.

Enrolment in another study that would conflict with the current study

I cannot take dual antiplatelet therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either genotype-guided P2Y12 inhibitor selection or conventional Clopidogrel therapy for 90 days

12 weeks

Baseline visit, Day 90 visit

Follow-up

Participants are monitored for safety and effectiveness after treatment, including brain scans and cognitive assessments

4 weeks

Day 90 ± 14 follow-up visit

What Are the Treatments Tested in This Trial?

Interventions

• Clopidogrel
• Ticagrelor

Trial Overview The trial tests if using genetic testing to choose between two blood-thinning medications—Ticagrelor or Clopidogrel—can prevent further strokes in ICAD patients. One group gets standard care with Clopidogrel; the other gets Ticagrelor based on their gene test results.

How Is the Trial Designed?

Group I: Point-of-Care CYP2C19 Testing Experimental Treatment 3 Interventions

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).

Group II: Standard of Care Active Control 1 Intervention

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

Clopidogrel is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Approved in United States as Plavix for:

• Reduction of myocardial infarction and stroke in patients with acute coronary syndrome
• Reduction of myocardial infarction and stroke in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease

Approved in Canada as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Approved in Japan as Plavix for:

• Prevention of recurrence of ischemic cerebrovascular disorder
• Prevention of recurrence of myocardial infarction

Approved in China as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

Ticagrelor (Brilinta) has been approved by the FDA as an oral antiplatelet medication to be used with low-dose aspirin for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS).

Ticagrelor will compete with existing medications like clopidogrel (Plavix) and prasugrel (Effient), especially as clopidogrel is expected to become available as a generic option soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? [2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11743172/

Comparing efficacy and safety of low-dose versus standard ... Low-dose antiplatelet therapy significantly reduces the risk of bleeding compared to standard doses, with consistent risks of stroke, MI, ACD, major bleeding, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309137

Dual Antiplatelet Treatment up to 72 Hours after Ischemic ... Combined clopidogrel–aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2823299

Clopidogrel and Aspirin Initiated Between 24 to 72 Hours ... The results of this study suggest that patients with mild ischemic stroke or TIA can benefit from dual antiplatelet therapy with clopidogrel and aspirin when ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.033611

Trends in Dual Antiplatelet Therapy of Aspirin and ... From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, ...

5. strokebestpractices.ca strokebestpractices.ca/recommendations/secondary-prevention-of-stroke/anti-platelet-therapy-in-ischemic-stroke-and-tia

6. Antiplatelet Therapy for Ischemic Stroke and Transient ... The short-term use of the combination of clopidogrel + aspirin vs. aspirin alone, has been shown to reduce the risk of additional ischemic vascular events ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1800410

Clopidogrel and Aspirin in Acute Ischemic Stroke and High ... Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000003941

Risks and benefits of clopidogrel–aspirin in minor stroke or ... Clopidogrel–aspirin therapy numerically reduced the risk of new ischemic stroke within the first 2 weeks, but numerically increased the risk of new stroke ...