Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis
Condition: Ischemic Stroke
MeSH terms: Stroke; Ischemic Stroke
Intervention: intracranial angioplasty and stenting; intensive medical management
Intervention description: 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).; 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)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 451.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: ischemic stroke; intracranial stenting; vascular risk factor management

Summary:

      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.
    

Eligibility 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