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.
Trial Stopped: Pre-specified futility boundary was reached.
- STA-MCA bypass Procedure/Surgery
Intervention Desc: Surgical anastamosis between superficial temporal artery and middle cerebral artery.
- Best Medical Therapy Drug
Intervention Desc: best current practice medical therapy ARM 1: Kind: Experimental Label: Non-surgical group Description: Receives best current practice medical therapy
- Extracranial-intracranial bypass surgery Procedure
Other Names: STA-MCA Bypass and EDMS Intervention Desc: Surgical anastomosis of a superficial temporal artery branch to a middle cerebral artery branch through a small craniectomy plus best current practice medical therapy ARM 1: Kind: Experimental Label: Surgical group Description: Assigned to undergo extracranial-intracranial arterial bypass in addition to best current practice medical therapy
- Allocation: Randomized
- Masking: Single Blind (Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Efficacy Study
- Intervention: Parallel Assignment
All patients will receive PET scans, and, if indicated, arteriograms. Patients whose PET results indicate increased oxygen extraction will be randomized to either best medical treatment alone, or STA-MCA anastomosis in conjunction with best medical treatment. Follow-up includes clinic visits at 1 month, 3 months and every 3 months for 2 years. All participants will receive best medical management, which includes management of hypertension and other medical risk factors.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Combined incidence of stroke and death at 30 days post-treatment; incidence of ipsilateral ischemic stroke at 2 years.|
|Secondary||Incidences of all stroke, disabling stroke, fatal stroke, and death; National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (MRS), BI, and Stroke-Specific Quality of Life (SSQol) scores.|
|Primary||Surgical group:combination of the occurrence of ipsilateral ischemic stroke within 2 yrs of randomization and of all stroke & death from surgery through 30 days post operation||within 2 yrs of randomization||No|
|Primary||Non-surgical group: combination of the occurrence of ipsilateral ischemic stroke within 2 yrs of randomization and of all stroke & death from randomization through 30 days post randomization||within 2 yrs of randomization||No|
|Secondary||all stroke, disabling stroke, fatal stroke, death, Rankin Scale, NIHSS, modified Barthel Index and SS-QOL Quality of Life assessment||within two years after randomization||No|
|Primary||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||within 2 yrs of randomization||No|
|Secondary||All Stroke||within 2 yrs of randomization||No|
|Secondary||Disabling Stroke||within two years after randomization||No|
|Secondary||Fatal Stroke||within 2 years after randomization||No|
|Secondary||Death||within 2 years after randomization||No|
|Secondary||Modified Rankin 0-1||at 2 years after randomization or end of trial. Worst case imputed for death and missing values||No|
|Secondary||Modified Rankin 0-2||at 2 years after randomization or end of trial. Worst case imputed for death and missing values||No|
|Secondary||Modified Barthel Index 19-20||at 2 years after randomization or end of trial. Worst case imputed for death and missing values||No|
|Secondary||Summary SS-QOL Score||at 2 years after randomization or end of trial. Worst case imputed for death and missing values||No|
|Secondary||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||within 2 years of randomization||No|