Clinical trial NCT00029146: Carotid Occlusion Surgery Study
Official title: Carotid Occlusion Surgery Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Stroke
Ischemic Attack, Transient
Cerebral Infarction
Keywords: stroke
transient ischemic attack (TIA)
carotid arteries
cerebral infarction
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Washington University School of Medicine
name: University of Iowa
First posted: 2002-01-09
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Vascular imaging demonstrating occlusion of one or both internal carotid arteries.
* Transient ischemic attack (TIA) or ischemic stroke in the hemispheric carotid territory of one occluded carotid artery.
* Most recent qualifying TIA or stroke occurring within 120 days prior to projected performance date of PET.
* Modified Barthel Index \> 12/20 (60/100).
* Language comprehension intact, motor aphasia mild or absent.
* Age 18-85 inclusive.
* Competent to give informed consent.
* Legally an adult.
* Geographically accessible and reliable for follow-up.

Exclusion Criteria:

* Non-atherosclerotic carotid vascular disease. Blood dyscrasias: Polycythemia vera ,essential thrombocytosis, sickle cell disease (SS or SC).
* Known heart disease likely to cause cerebral ischemia (echocardiography not required). This includes the following conditions ONLY: Prosthetic valve, Infective endocarditis, Left atrial or ventricular thrombus, Sick sinus syndrome, Myxoma, Cardiomyopathy with ejection fraction \<25%. This is an all-inclusive list. The following conditions are NOT EXCLUSIONS: Atrial fibrillation, patent foramen ovale, atrial septal aneurysm.
* Other non-atherosclerotic condition likely to cause focal cerebral ischemia.
* Any condition likely to lead to death within 2 years.
* Other neurological disease that would confound follow-up assessment.
* Pregnancy.
* Subsequent cerebrovascular surgery planned which might alter cerebral hemodynamics.
* Any condition which in the participating surgeon's judgment makes the subject an unsuitable surgical candidate.
* Participation in any other experimental treatment trial.
* Participation within the previous 12 months in any experimental study that included exposure to ionizing radiation.
* Acute, progressing or unstable neurological deficit. Neurological deficit must be stable for 72 hours prior to the performance of PET.
* If supplemental arteriography is required, allergy to iodine or x-ray contrast media, serum creatinine \> 3.0 mg/dl or other contraindication to arteriography.
* If aspirin is to be used as antithrombotic therapy in the perioperative period, those with allergy or contraindication to aspirin are ineligible.
* Medical indication for treatment with anticoagulant drugs, ticlopidine, clopidogrel or other antithrombotic medications such that these medications cannot be replaced with aspirin in the perioperative period as deemed necessary by the COSS neurosurgeon if the participant is randomized to surgical treatment.
* Remediable medical conditions. Patients with the following conditions can become eligible if the exclusion criterion no longer applies within 120 days of onset of the most recent qualifying event: Uncontrolled diabetes mellitus (FBS \> 300 mg%/16.7 mmol/L), Uncontrolled hypertension (systolic BP\>180, diastolic BP \>110), Unstable angina, Uncontrolled hypotension (diastolic BP \< 65).

Primary outcomes:
measure: 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
timeFrame: within 2 yrs of randomization
Secondary outcomes:
measure: All Stroke
timeFrame: within 2 yrs of randomization
measure: Disabling Stroke
timeFrame: within two years after randomization
measure: Fatal Stroke
timeFrame: within 2 years after randomization
measure: Death
timeFrame: within 2 years after randomization
measure: Modified Rankin 0-1
timeFrame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
measure: Modified Rankin 0-2
timeFrame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
measure: Modified Barthel Index 19-20
timeFrame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
measure: Summary SS-QOL Score
timeFrame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values
measure: 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
timeFrame: within 2 years of randomization
Other outcomes:
measure: Any Stroke or Death Within 30 Days After Surgery
timeFrame: within 30 days after surgery
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: William J. Powers, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grubb RL Jr, Derdeyn CP, Fritsch SM, Carpenter DA, Yundt KD, Videen TO, Spitznagel EL, Powers WJ. Importance of hemodynamic factors in the prognosis of symptomatic carotid occlusion. JAMA. 1998 Sep 23-30;280(12):1055-60. doi: 10.1001/jama.280.12.1055.
citation: Derdeyn CP, Gage BF, Grubb RL Jr, Powers WJ. Cost-effectiveness analysis of therapy for symptomatic carotid occlusion: PET screening before selective extracranial-to-intracranial bypass versus medical treatment. J Nucl Med. 2000 May;41(5):800-7.
citation: Adams HP Jr, Powers WJ, Grubb RL Jr, Clarke WR, Woolson RF. Preview of a new trial of extracranial-to-intracranial arterial anastomosis: the carotid occlusion surgery study. Neurosurg Clin N Am. 2001 Jul;12(3):613-24, ix-x.
citation: Grubb RL Jr, Powers WJ, Derdeyn CP, Adams HP Jr, Clarke WR. The Carotid Occlusion Surgery Study. Neurosurg Focus. 2003 Mar 15;14(3):e9. doi: 10.3171/foc.2003.14.3.10.
citation: Grubb RL Jr, Powers WJ, Clarke WR, Videen TO, Adams HP Jr, Derdeyn CP; Carotid Occlusion Surgery Study Investigators. Surgical results of the Carotid Occlusion Surgery Study. J Neurosurg. 2013 Jan;118(1):25-33. doi: 10.3171/2012.9.JNS12551. Epub 2012 Oct 26.
citation: Powers WJ, Clarke WR, Grubb RL Jr, Videen TO, Adams HP Jr, Derdeyn CP; COSS Investigators. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA. 2011 Nov 9;306(18):1983-92. doi: 10.1001/jama.2011.1610.