Carotid Occlusion Surgery Study (COSS)

This study has been terminated.
(Pre-specified futility boundary was reached.)
Sponsor:
Collaborators:
Washington University School of Medicine
University of Iowa
Information provided by (Responsible Party):
William Powers, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00029146
First received: January 8, 2002
Last updated: March 24, 2012
Last verified: March 2012
  Purpose

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).


Condition Intervention Phase
Stroke
Ischemic Attack, Transient
Cerebral Infarction
Procedure: extracranial-intracranial bypass surgery
Drug: best medical therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Carotid Occlusion Surgery Study

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

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 [ Time Frame: within 2 yrs of randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 2 yrs of randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: within two years after randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 2 years after randomization ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 2 years after randomization ] [ Designated as safety issue: No ]
    2 yr Kaplan-Meier estimates of the proportions. Death of any cause

  • Modified Rankin 0-1 [ Time Frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 2 years after randomization or end of trial. Worst case imputed for death and missing values ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 2 years of randomization ] [ Designated as safety issue: No ]
    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.


Enrollment: 700
Study Start Date: July 2002
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Surgical group
Assigned to undergo extracranial-intracranial arterial bypass in addition to best current practice medical therapy
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
Other Names:
  • EC-IC Arterial Bypass
  • STA-MCA Bypass
Active Comparator: Non-surgical group
Receives best current practice medical therapy
Drug: best medical therapy
best current practice medical therapy

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00029146

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Washington University School of Medicine
University of Iowa
Investigators
Principal Investigator: William J. Powers, M.D. University of North Carolina, Chapel Hill
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: William Powers, Professor of Neurology, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00029146     History of Changes
Other Study ID Numbers: R01NS042167, R01NS041895
Study First Received: January 8, 2002
Results First Received: January 17, 2012
Last Updated: March 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
stroke
transient ischemic attack (TIA)
carotid arteries
cerebral infarction

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Ischemic Attack, Transient
Infarction
Ischemia
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Necrosis

ClinicalTrials.gov processed this record on July 28, 2014