Carotid Occlusion Surgery Study

Stroke Clinical Trial

— COSS  

Official title:

Carotid Occlusion Surgery Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00029146
• Other study ID #: R01NS042167
• Secondary ID: R01NS041895
• Status: Terminated
• Phase: Phase 3
• First received: January 8, 2002
• Last updated: March 24, 2012
• Start date: July 2002
• Est. completion date: June 2010

Study information

• Verified date: March 2012
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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 (

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 700
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Infarction
• Infarction
• Ischemic Attack, Transient
• Stroke

Intervention

Procedure:
• extracranial-intracranial bypass surgery
Surgical anastomosis of a superficial temporal artery branch to a middle cerebral artery branch through a small craniectomy plus best current practice medical therapy

Drug:
• best medical therapy
best current practice medical therapy

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (4)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Neurological Disorders and Stroke (NINDS), University of Iowa, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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	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.	within 2 yrs of randomization	No
Secondary	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	within 2 yrs of randomization	No
Secondary	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	within two years after randomization	No
Secondary	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	within 2 years after randomization	No
Secondary	Death	2 yr Kaplan-Meier estimates of the proportions. Death of any cause	within 2 years after randomization	No
Secondary	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.	at 2 years after randomization or end of trial. Worst case imputed for death and missing values	No
Secondary	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.	at 2 years after randomization or end of trial. Worst case imputed for death and missing values	No
Secondary	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.	at 2 years after randomization or end of trial. Worst case imputed for death and missing values	No
Secondary	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.	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	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.	within 2 years of randomization	No