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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the drug Clopidogrel for stroke treatment?

Research shows that Clopidogrel can help prevent strokes, especially when used with aspirin, but its effectiveness can vary based on genetic factors. People with certain genetic variants may not respond well to Clopidogrel, so genetic testing can help identify those who might need a different treatment. ^{1 2 3 4 5}

Is genetic testing for stroke treatment using Clopidogrel or Ticagrelor safe?

Clopidogrel and Ticagrelor are generally safe for use in humans, but their effectiveness can vary based on genetic factors. Some people with certain genetic variants may not respond well to Clopidogrel, which could increase the risk of stroke or heart attack, so genetic testing can help identify those who might need alternative treatments. ^{1 3 4 6 7}

How does the drug Clopidogrel differ from other stroke treatments?

Clopidogrel is unique because its effectiveness can vary based on a person's genetic makeup, specifically the CYP2C19 gene, which affects how the drug is metabolized in the body. Genetic testing can help identify patients who may not respond well to Clopidogrel, allowing for personalized treatment plans to improve outcomes. ^{3 4 8 9 10}

Research Team

Mark I Boulos, MD, MSc

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Establishment of a CYP2C19 genotyping assay for clinical use. [2019]

2. Poland pubmed.ncbi.nlm.nih.gov

Effects of CYP2C19 and P2Y12 Gene Polymorphisms on Clinical Results of Patients Using Clopidogrel after Acute Ischemic Cerebrovascular Disease. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Genetic testing for CYP450 polymorphisms to predict response to clopidogrel: current evidence and test availability. Application: pharmacogenomics. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

F2R Polymorphisms and Clopidogrel Efficacy and Safety in Patients With Minor Stroke or TIA. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Ticagrelor Aspirin vs Clopidogrel Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Thromboelastographic and Gene Polymorphism Bimodality Detection for Dual Antiplatelet Aggregation Therapy in Individuals with Clopidogrelresistant Symptomatic Intracranial Artery Stenosis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CYP2C19 genotype in stroke or transient ischemic attack patients treated with clopidogrel monotherapy or clopidogrel plus aspirin: Protocol for a systemic review and meta-analysis. [2023]

10. China pubmed.ncbi.nlm.nih.gov

[Status quo and countermeasure of clopidogrel resistance predicted by gene testing]. [2019]