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

Официальное название

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

Обзор

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.

Вмешательства

• Генная терапия Point-of-Care CYP2C19 Testing
  Genetic testing with the Genomadix cube to determine P2Y12 inhibitor
• Препарат ticagrelor + aspirin
  If patients are poor or intermediate metabolizers of clopidogrel, they will receive ticagrelor (90 mg PO BID) + aspirin (81 mg PO daily)
• Препарат 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.

Первичные конечные точки

• Rate of recruitment [Срок оценки: Through study completion, an average of 90 days]
• Rate of study completion [Срок оценки: Through study completion, an average of 90 days]
• Rate of protocol deviations [Срок оценки: Through study completion, an average of 90 days]
• Proportion of patients with Symptomatic intracerebral hemorrhage (ICH) [Срок оценки: Through study completion, an average of 90 days]
• Proportion of patients with major extracranial bleeding [Срок оценки: Through study completion, an average of 90 days]
• Proportion of patients with non-bleeding adverse events [Срок оценки: Through study completion, an average of 90 days]

Вторичные конечные точки (10)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Канада · 2 центра

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

Идентификаторы

NCT: NCT06714526 · 5902

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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