Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Marc Chimowitz, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00576693
First received: December 7, 2007
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

PRIMARY HYPOTHESIS:

Compared with intensive medical therapy alone, intracranial angioplasty and stenting combined with intensive medical therapy will decrease the risk of the primary endpoint by 35% over a mean follow-up of two years in high-risk patients patients with 70% - 99% intracranial stenosis who had a transient ischemic attack (TIA) or stroke within 30 days prior to enrollment) with symptomatic stenosis of a major intracranial artery.

SUMMARY:

The best treatment for prevention of another stroke or TIA in patients with narrowing of one of the arteries in the brain is uncertain. A common treatment is the use of anti-clotting medications to prevent blood clots from forming in the narrowed vessel. There are a variety of medicines used for this purpose. These medications are usually taken for the rest of a patient's life.

However, a treatment that has been used successfully together with anti-clotting medications in patients with narrowing of the blood vessels of the heart is now being studied in the blood vessels of the brain. This treatment is called stenting.

Recent research has also indicated a benefit in prevention of recurring stroke by Intensive Medical Therapy, which is defined as treating risk factors for stroke like high blood pressure, elevated LDL (low density lipids - the "bad" form of cholesterol) and diabetes. The purpose of this study is to compare the safety and effectiveness of either Intensive Medical Therapy PLUS Stenting or Intensive Medical Therapy ONLY in preventing stroke, heart attacks or death.

The study will enroll patients over a 5 year period. Each participant will be involved in the study for a minimum of 1 year and a maximum of 3 years.

Fifty different medical centers in the United States are part of this study. Both the Clinical Coordinating Center and the Statistical Coordinating Center for the entire study will be located at Emory University.


Condition Intervention Phase
Ischemic Stroke
Device: intracranial angioplasty and stenting
Other: intensive medical management
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Any Stroke or Death Within 30 Days of Enrollment or Any Revascularization Procedure OR an Ischemic Stroke in the Territory of the Symptomatic Intracranial Artery Beyond 30 Days After Enrollment. [ Time Frame: Mean length of follow-up was 2.4 years ] [ Designated as safety issue: Yes ]
    Any stroke (ischemic, parenchymal brain hemorrhage, subarachnoid or intraventricular hemorrhage) or death within 30 days after enrollment OR any stroke (ischemic, parenchymal brain hemorrhage, subarachnoid or intraventricular hemorrhage) or death within 30 days of any revascularization procedure of the qualifying symptomatic intracranial artery done during follow-up, OR an ischemic stroke in the territory of the symptomatic intracranial artery from day 31 after study entry to completion of follow-up.


Enrollment: 451
Study Start Date: October 2008
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intensive medical management plus stenting
intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl).
Device: intracranial angioplasty and stenting
intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl).
Other Names:
  • Wingspan stent
  • Gateway balloon
Experimental: intensive medical management alone
Intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)
Other: intensive medical management
intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)

Detailed Description:

This will be an investigator initiated and designed Phase III multicenter trial in which patients with TIA or non-disabling stroke within 30 days prior to enrollment that is caused by 70% - 99% stenosis of a major intracranial artery (MCA, carotid, vertebral, or basilar) will be randomized (1:1) at approximately 50 sites to:

intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl)

OR

intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl).

Risk factor management will be performed by the study neurologist at each site who will be assisted by an innovative, evidence-based, educational, lifestyle modification program (INTERxVENT) that will be administered at regularly scheduled times to all patients throughout the study.

All patients enrolled in the trial will be followed until the first of the following: 90 days after a primary endpoint, death, or the close-out visit in the trial, which will occur within a window from 60 days before March 31, 2012 to 30 days after March 31, 2013. Patients who do not die or have a primary endpoint during follow-up will be followed for 2-4.5 years.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  1. Transient ischemic attack (TIA) or non-severe stroke within 30 days of enrollment attributed to 70-99% stenosis of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery)

    • may be diagnosed byTranscranial Doppler (TCD), Magnetic Resonance Angiogram (MRA), or computed tomography angiography (CTA) to qualify for angiogram performed as part of the study protocol but must be confirmed by catheter angiography for enrollment in the trial

  2. Modified Rankin score of ≤ 3
  3. Target area of stenosis in an intracranial artery that has a normal diameter of 2.00 mm to 4.50 mm
  4. Target area of stenosis is less than or equal to 14 mm in length
  5. Age ≥ 30 years and ≤ 80 years.

    • Patients 30-49 years are required to meet at least one additional criteria (i-vi) provided in the table below to qualify for the study. This additional requirement is to increase the likelihood that the symptomatic intracranial stenosis in patients 30-49 years is atherosclerotic.

    i. insulin dependent diabetes for at least 15 years ii. at least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL < 40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event ii. history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease iv. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic

  6. Negative pregnancy test in a female who has had any menses in the last 18 months
  7. Patient is willing and able to return for all follow-up visits required by the protocol
  8. Patient is available by phone
  9. Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent

EXCLUSION CRITERIA

  1. Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion (NOTE: an exception is allowed if the occlusion involves a single vertebral artery proximal to a symptomatic basilar artery stenosis and the contralateral vertebral artery is supplying the basilar artery)
  2. Bilateral intracranial vertebral artery stenosis of 70%-99% and uncertainty about which artery is symptomatic (e.g. if patient has pontine, midbrain, or temporal - occipital symptoms)
  3. Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days prior to expected enrollment date
  4. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion
  5. Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis
  6. Presence of intraluminal thrombus proximal to or at the target lesion
  7. Any aneurysm proximal to or distal to stenotic intracranial artery
  8. Intracranial tumor (except meningioma) or any intracranial vascular malformation
  9. CT or angiographic evidence of severe calcification at target lesion
  10. Thrombolytic therapy within 24 hours prior to enrollment
  11. Progressive neurological signs within 24 hours prior to enrollment
  12. Brain infarct within previous 30 days of enrollment that is of sufficient size (> 5 cms) to be at risk of hemorrhagic conversion during or after stenting
  13. Any hemorrhagic infarct within 14 days prior to enrollment
  14. Any hemorrhagic infarct within 15 - 30 days that is associated with mass effect
  15. Any history of a primary intracerebral (parenchymal) hemorrhage (ICH)
  16. Any other intracranial hemorrhage (subarachnoid, subdural, epidural) within 30 days
  17. Any untreated chronic subdural hematoma of greater than 5 mm in thickness
  18. Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with Cerebrospinal fluid (CSF) pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus
  19. Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30%
  20. Known allergy or contraindication to aspirin, clopidogrel, heparin, nitinol, local or general anesthesia
  21. History of life-threatening allergy to contrast dye. If not life threatening and can be effectively pretreated, patient can be enrolled at physician's discretion
  22. Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets < 100,000, hematocrit < 30, International normalized ratio (INR) > 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), severe liver impairment Aspartate Transaminase (AST) or Alanine transaminase (ALT) > 3 x normal, cirrhosis, creatinine > 3.0 (unless on dialysis)
  23. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment
  24. Indication for warfarin or heparin beyond enrollment (NOTE: exceptions allowed for use of systemic heparin during stenting procedure or subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis while hospitalized)
  25. Severe neurological deficit that renders the patient incapable of living independently
  26. Dementia or psychiatric problem that prevents the patient from following an outpatient program reliably
  27. Co-morbid conditions that may limit survival to less than 3 years
  28. Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study
  29. Enrollment in another study that would conflict with the current study
  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: NCT00576693

  Hide Study Locations
Locations
United States, Alabama
UAB Medical Center
Birmingham, Alabama, United States, 35294
United States, Arizona
Barrow Neurological Institute - St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
Mayo
Phoenix, Arizona, United States, 85054
United States, California
Glendale Adventist
Glendale, California, United States, 91203
Cedars Sinai
Los Angeles, California, United States, 90048
UCLA
Los Angeles, California, United States, 90095
UCSF
San Francisco, California, United States, 94143
United States, District of Columbia
Washington Hospital
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida - Shands
Gainesville, Florida, United States, 32611
University of Miami
Miami, Florida, United States, 33136
Florida Hospital
Winter Park, Florida, United States, 32789
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30388
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Central DuPage Hospital
Winfield, Illinois, United States, 60190
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Medical Center
Detroit, Michigan, United States, 48202
Wayne State
Detroit, Michigan, United States, 48201
Providence St. John
Southfield, Michigan, United States, 48075
United States, Mississippi
University of Mississippi
Jackson, Mississippi, United States, 39216
United States, New York
University of Buffalo
Buffalo, New York, United States, 14209
Columbia University Medical Center
New York, New York, United States, 10032
Cornell Medical College
New York, New York, United States, 10065
NYU Medical Center
New York, New York, United States, 10016
Stony Brook University Medical Center
Stony Brook, New York, United States, 11790
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
Moses Cone Medical Center
Greensboro, North Carolina, United States, 27401
Forsyth Medical Center
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
Cleveland Clinic
Cleveland, Ohio, United States, 44195
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Riverside Methodist
Columbus, Ohio, United States, 43214
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19170
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburg, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Erlanger Medical Center
Chattanooga, Tennessee, United States, 37403
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
UT Southwestern
Dallas, Texas, United States, 75390
Baylor St. Luke's
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
Scott & White - Texas A&M
Temple, Texas, United States, 76508
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
Sentera
Norfolk, Virginia, United States, 23507
United States, Washington
Sacred Heart Medical Center
Spokane, Washington, United States, 99204
MultiCare
Tacoma, Washington, United States, 98405
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Marc Chimowitz
Investigators
Principal Investigator: Marc I Chimowitz, MBChB Medical University of South Carolina
  More Information

Additional Information:
Publications:

Responsible Party: Marc Chimowitz, Full Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00576693     History of Changes
Other Study ID Numbers: R01NS058728-01A1, NINDS, CRC, 1U01NS058728-01A1
Study First Received: December 7, 2007
Results First Received: May 6, 2014
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Medical University of South Carolina:
ischemic stroke
intracranial stenting
vascular risk factor management

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Clopidogrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014