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

Official 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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Rate of recruitment [Time frame: Through study completion, an average of 90 days]
• Rate of study completion [Time frame: Through study completion, an average of 90 days]
• Rate of protocol deviations [Time frame: 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]
• Proportion of patients with major extracranial bleeding [Time frame: 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]

Secondary outcome measures (10)

• Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound [Time frame: Day 5 ± 2]
• Change in volume of ischemic strokes and white matter hyperintensities (optional) [Time frame: Day 0 + 14 and Day 90 ± 14]
• Change in number of ischemic strokes and white matter hyperintensities [Time frame: Day 0 + 3 and Day 90 ± 14]
• Number of patients with ischemic stroke, myocardial infarction, or death [Time frame: Day 90 ± 14]
• Change in Montreal Cognitive Assessment (MoCA) score from baseline to follow-up [Time frame: 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]
• Change or shift in modified Rankin Scale (mRS) score from baseline to follow-up [Time frame: Day 0 and Day 90 ± 14]
• Self-reported Quality of Life as assessed by the EQ-5D-5L [Time frame: Day 90 ± 14]
• Self-reported Dementia Screening assessed by the AD8 Dementia Screening Interview [Time frame: Day 90 ± 14]
• Self-reported functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living Scale [Time frame: Day 90 ± 14]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 2 centers

• University of Calgary — Calgary
• Dr. Mark I. Boulos - Sunnybrook Health Sciences Centre — Toronto

Identifiers

NCT: NCT06714526 · 5902

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗