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Carotid Occlusion Surgery Study (COSS)

Primary Purpose

Stroke, Ischemic Attack, Transient, Cerebral Infarction

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
extracranial-intracranial bypass surgery
best medical therapy
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring stroke, transient ischemic attack (TIA), carotid arteries, cerebral infarction

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Surgical group

Non-surgical group

Arm Description

Assigned to undergo extracranial-intracranial arterial bypass in addition to best current practice medical therapy

Receives best current practice medical therapy

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
Death
2 yr Kaplan-Meier estimates of the proportions. Death of any cause
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.
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.
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.
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.
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.

Full Information

First Posted
January 8, 2002
Last Updated
March 24, 2012
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Washington University School of Medicine, University of Iowa
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1. Study Identification

Unique Protocol Identification Number
NCT00029146
Brief Title
Carotid Occlusion Surgery Study
Acronym
COSS
Official Title
Carotid Occlusion Surgery Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Why Stopped
Pre-specified futility boundary was reached.
Study Start Date
July 2002 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Washington University School of Medicine, University of Iowa

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Ischemic Attack, Transient, Cerebral Infarction
Keywords
stroke, transient ischemic attack (TIA), carotid arteries, cerebral infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
700 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Surgical group
Arm Type
Experimental
Arm Description
Assigned to undergo extracranial-intracranial arterial bypass in addition to best current practice medical therapy
Arm Title
Non-surgical group
Arm Type
Active Comparator
Arm Description
Receives best current practice medical therapy
Intervention Type
Procedure
Intervention Name(s)
extracranial-intracranial bypass surgery
Other Intervention Name(s)
EC-IC Arterial Bypass, STA-MCA Bypass
Intervention Description
Surgical anastomosis of a superficial temporal artery branch to a middle cerebral artery branch through a small craniectomy plus best current practice medical therapy
Intervention Type
Drug
Intervention Name(s)
best medical therapy
Intervention Description
best current practice medical therapy
Primary Outcome Measure Information:
Title
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
Description
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
Secondary Outcome Measure Information:
Title
All Stroke
Description
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
Title
Disabling Stroke
Description
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
Title
Fatal Stroke
Description
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
Title
Death
Description
2 yr Kaplan-Meier estimates of the proportions. Death of any cause
Time Frame
within 2 years after randomization
Title
Modified Rankin 0-1
Description
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
Title
Modified Rankin 0-2
Description
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
Title
Modified Barthel Index 19-20
Description
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
Title
Summary SS-QOL Score
Description
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
Title
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
Description
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
Other Pre-specified Outcome Measures:
Title
Any Stroke or Death Within 30 Days After Surgery
Time Frame
within 30 days after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William J. Powers, M.D.
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9757852
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.
Results Reference
background
PubMed Identifier
10809195
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.
Results Reference
background
PubMed Identifier
11390318
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.
Results Reference
background
PubMed Identifier
15709726
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.
Results Reference
background
PubMed Identifier
23101451
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.
Results Reference
derived
PubMed Identifier
22068990
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. Erratum In: JAMA. 2011 Dec 28;306(24):2672. Obviagele, Bruce [corrected to Ovbiagele, Bruce].
Results Reference
derived

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Carotid Occlusion Surgery Study

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