The purpose of this study is to determine if extracranial-intracranial bypass surgery when added to best medical therapy can reduce the subsequent risk of ipsilateral stroke in high-risk patients with recently symptomatic carotid occlusion and increased cerebral oxygen extraction fraction measured by positron emission tomography (PET).
The overall purpose of this research is to determine if a surgical operation called "Extracranial-Intracranial Bypass" can reduce the chance of a subsequent stroke in someone who has complete blockage in one main artery in the neck (the carotid artery) that supplies blood to the brain and has already suffered a small stroke. This surgery involves taking an artery from the scalp outside the skull, making a small hole in the skull and then connecting the scalp artery to a brain artery inside the skull. In this way the blockage of the carotid artery in the neck is bypassed and more blood can flow to the brain. In some people natural bypass arteries develop and the brain is already getting plenty of blood. These people have a low risk of stroke if they take medicine. In other people, no natural bypass arteries develop so less blood flows to their brains. This second group has a much higher risk of stroke while taking medicine, as high as 25-50% within the next two years. It is this second group of people who may benefit from having the bypass operation and who are the candidates for this study. This bypass surgery is considered experimental because it is not generally performed for this condition and it is unknown whether it leads to a decrease, an increase or no change in the risk of stroke. In order to determine if people fit into this second group of people who may benefit from the bypass operation they need to have a test called a PET scan. The PET scan measures the amount of blood that is getting to the brain and the amount of oxygen that the brain is using. The PET scan uses radioactive oxygen and water and is experimental (not approved by the United States Food and Drug Administration). If the PET scan shows that less blood is getting to the brain, there will be a 50-50 chance (like a coin toss) of receiving the bypass surgery or not. There will then be follow-up visits to the clinic one month later and then every three months for two years to check on the appropriate medical treatment that everyone will receive and to determine who has had a stroke. The study hypothesis is that extracranial-intracranial bypass surgery when added to best medical therapy can reduce by 40 percent subsequent stroke within two years in participants with recent TIA ('ministroke") or stroke (\</= 120 days) due to blockage of the carotid artery and reduced blood flow to the brain measured by PET.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
700
Surgical anastomosis of a superficial temporal artery branch to a middle cerebral artery branch through a small craniectomy plus best current practice medical therapy
best current practice medical therapy
Washington University School of Medicine
St Louis, Missouri, United States
Surgical Group:Ipsilateral Ischemic Stroke in 2 Yrs From Randomization and All Stroke & Death Through 30d Post-surgery; Non-surgical Group:Ipsilateral Ischemic Stroke in 2 Yrs From Randomization and All Stroke & Death Through 30d Post-randomization
2 yr Kaplan-Meier estimates of the proportions.Proportions expressed as percentages for reporting purposes. Ipsilateral ischemic stroke is defined as the clinical diagnosis of a focal neurological deficit due to cerebral ischemia clinically localizable within the internal carotid artery territory distally to the symptomatic occluded internal carotid artery that lasts for more than 24 hours. All stroke is defined as the clinical diagnosis of a focal deficit due to ischemia or hemorrhage clinically localizable to the brain that lasts for more than 24 hours. Death is of any cause.
Time frame: within 2 yrs of randomization
All Stroke
2 yr Kaplan-Meier estimates of the proportions. All stroke is defined as the clinical diagnosis of a focal deficit due to ischemia or hemorrhage clinically localizable to the brain that lasts for more than 24 hours
Time frame: within 2 yrs of randomization
Disabling Stroke
2 yr Kaplan-Meier estimates of the proportions. Disabling stroke is defined as a modified Barthel Index of \<12/20 at the first scheduled return visit more than 3 months after the stroke occurred
Time frame: within two years after randomization
Fatal Stroke
2 yr Kaplan-Meier estimates of the proportions. Fatal stroke is a stroke that in the investigator's opinion led directly to the participants death within 30 days of occurrence
Time frame: within 2 years after randomization
Death
2 yr Kaplan-Meier estimates of the proportions. Death of any cause
Time frame: within 2 years after randomization
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Modified Rankin 0-1
Proportion with modified Rankin score, dichotomized 0 or 1 vs 2-6.The modifed Rankin (0-6) describes the degree of functional disability. A lower score indicates less functional disability.
Time frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
Modified Rankin 0-2
Proportion with Modified Rankin score at 2 yrs, dichotomized 0-2 vs 3-6. The modifed Rankin (0-6) describes the degree of functional disability. A lower score indicates less functional disability.
Time frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
Modified Barthel Index 19-20
Modified Barthel Index dichotomized 19-20 vs \<= 18. The modifed Barthel Index(0-20) describes the degree of independence in day-to-day self-care activities. A higher score indicates greater independence.
Time frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
Summary SS-QOL Score
Summary Stroke Specific Quality of Life score (1-4) askes how self-reported overall quality of life compares with with that before stroke. A higher score indicates is better.
Time frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
Ipsilateral Ischemic Stroke in 2 Yrs From Randomization and All Stroke & Death Through 30d Post-surgery; Non-surgical Group:Ipsilateral Ischemic Stroke in 2 Yrs From Randomization and All Stroke & Death Through 30d Post-randomization
2 yr Kaplan-Meier estimates of the proportions.Proportions expressed as percentages for reporting purposes. Ipsilateral ischemic stroke is defined as the clinical diagnosis of a focal neurological deficit due to cerebral ischemia clinically localizable within the internal carotid artery territory distally to the symptomatic occluded internal carotid artery that lasts for more than 24 hours. All stroke is defined as the clinical diagnosis of a focal deficit due to ischemia or hemorrhage clinically localizable to the brain that lasts for more than 24 hours. Death is of any cause.
Time frame: within 2 years of randomization