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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Rate of recruitment
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: Point-of-Care CYP2C19 Testing (Genetic)
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).
干预措施: ticagrelor + aspirin (Drug)
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).
干预措施: clopidogrel + aspirin (Drug)
结局指标
主要结局
Rate of recruitment
时间窗: Through study completion, an average of 90 days
The number of patients who provide informed consent, or are deemed ineligible after screening.
Rate of study completion
时间窗: Through study completion, an average of 90 days
The number of patients who complete the entire study protocol
Rate of protocol deviations
时间窗: Through study completion, an average of 90 days
The number of patients who encounter at least one protocol deviation during the study
Proportion of patients with Symptomatic intracerebral hemorrhage (ICH)
时间窗: 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
Proportion of patients with major extracranial bleeding
时间窗: 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
Proportion of patients with non-bleeding adverse events
时间窗: Through study completion, an average of 90 days
Non-bleeding adverse events related to the study drug including dyspnea, bradyarrhythmia, and/or chest pain
次要结局
- Proportion of patients who have Microembolic Signals on Transcranial Doppler Ultrasound(Day 5 ± 2)
- Change in volume of ischemic strokes and white matter hyperintensities (optional)(Day 0 + 14 and Day 90 ± 14)
- Change in number of ischemic strokes and white matter hyperintensities(Day 0 + 3 and Day 90 ± 14)
- Number of patients with ischemic stroke, myocardial infarction, or death(Day 90 ± 14)
- Change in Montreal Cognitive Assessment (MoCA) score from baseline to follow-up(Day 0 and Day 90 ± 14)
- Change in NIH Stroke Scale (NIHSS) score from baseline to follow-up(Day 0 and Day 90 ± 14)
- Change or shift in modified Rankin Scale (mRS) score from baseline to follow-up(Day 0 and Day 90 ± 14)
- Self-reported Quality of Life as assessed by the EQ-5D-5L(Day 90 ± 14)
- Self-reported Dementia Screening assessed by the AD8 Dementia Screening Interview(Day 90 ± 14)
- Self-reported functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living Scale(Day 90 ± 14)