EDAS Revascularization for Symptomatic Intracranial Atherosclerotic Steno-occlusive Disease

Prior treatment

• Angioplasty, stenting, or endarterectomy of an ipsilateral extracranial carotid artery within 90 days prior to enrollment or planned within 90 days following enrollment.
• TIAs of increased frequency, duration, or severity, or ischemic stroke within 7 days prior to enrollment.
• Infarct with hemorrhagic transformation within 30 days prior to enrollment.
• Infarct with hemorrhagic transformation of parenchymatous hematoma type-2 within 90 days prior to enrollment.
• Any other intracranial hemorrhage (subarachnoid, subdural, epidural) within 90 days prior to enrollment.
• Myocardial infarction within 1 month prior to enrollment.
• Other major surgery planned in the next 90 days after enrollment that may require suspension of antiplatelet therapy.

Other illness

• CT or MRI evidence of an isolated perforator stroke as qualifying event, defined by the Imaging Core based on established templates of cerebral vascular territories.
• History of primary intracerebral (parenchymal) hemorrhage.
• Intracranial stenosis due to non-atherosclerotic etiologies: evidence of arterial dissection; moyamoya 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; reversible cerebral vasoconstriction syndrome; postpartum angiopathy; suspected vasospastic process; suspected recanalized embolus.
• Unequivocal cardiac sources of embolism as stroke etiology, including chronic or paroxysmal atrial fibrillation, symptomatic ventricular arrhythmias, severe or symptomatic aortic or mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation.
• Unstable or severe angina.
• Known allergy or contraindication to general anesthesia.
• Known allergy to aspirin.
• Known life-threatening allergy to contrast dye.
• Uncontrolled severe hypertension (SBP \>180 mmHg or diastolic blood pressure \>115 mmHg).
• Dementia or a psychiatric problem that prevents the patient from reliably following an outpatient program.
• Co-morbid conditions that may limit survival to less than 3 years.
• Evidence of active untreated systemic or serious infections (i.e., pneumonia, complicated urinary infection).

Lab values

• Ejection fraction less than 40%.
• Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets \<100,000/mL, hematocrit \<30%, international normalized ratio \>1.5, clotting factor abnormality that increases the risk of bleeding.
• Severe liver impairment (AST or ALT \>3× normal, cirrhosis) that may prevent the use of statins.
• Severe renal impairment (creatinine \>3.0 mg/dL or on dialysis).

Other

• Stenting of the qualifying intracranial artery at any time, including a stent placed during an endovascular attempt for the qualifying event. Thrombectomy or angioplasty without stent placement is not an exclusion; eligibility is determined on imaging obtained after the procedure.
• Intracranial tumor or intracranial vascular malformation.
• Any untreated chronic subdural hematoma greater than 5 mm in thickness.
• Current alcohol or substance abuse within 1 month from enrollment.
• Pregnancy or of childbearing potential and unwilling to use contraception for the duration of the dual antiplatelet treatment period of the trial.
• Active enrollment in another therapeutic trial that would conflict with this trial.
• Body mass index (BMI) ≥40 kg/m2.

• Borderzone or superficial territorial ischemic stroke, or cortical TIA, within 30 days before enrollment, attributed to 70% to 100% atherosclerotic stenosis/occlusion of the intracranial ICA or the MCA (M1 or dominant/co-dominant M2). The eligible borderzone strokes are cortical (external) borderzone infarcts, located between the anterior and middle cerebral artery territories or between the middle and posterior cerebral artery territories; internal borderzone infarcts are not included. A cortical TIA is defined as transient cortical dysfunction evidenced by either visual field defects, spatial neglect, disorder of language, memory, or orientation. The corresponding cerebral artery atherosclerosis may be diagnosed by CTA, contrast-enhanced MRI, or catheter angiography.
• Evidence of perfusion impairment (minimum: TMax delay ≥ 6 sec, vol ≥ 5 cc) in CTP or perfusion MRI.
• Functional status better than severely disabled (mRS score 0-3).
• Age ≥18 years and ≤90 years. If the patient is 18 to 49 years of age, at least 1 of the following should be present:
  • Insulin-dependent diabetes for at least 15 years.
  • At least 2 of the following atherosclerotic risk factors: SBP ≥130 mmHg or on antihypertensive therapy; dyslipidemia (LDL \>130 mg/dL, HDL \<40 mg/dL, fasting triglycerides \>150 mg/dL, or on lipid-lowering therapy); smoking; non-insulin-dependent diabetes or insulin-dependent diabetes less than 15 years in duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary artery 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 years of age for women at the time of the event.
  • 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.
  • Any stenosis/occlusion 50% to 100% 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.
  • Aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography.
  • Any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic.
• Negative pregnancy test in a female who has had any menses 18 months prior to enrollment.
• Patient willing and able to return for all follow-up visits required by the protocol.
• Patient is available by telephone.
• Patient understands the purpose and requirements of the trial, can make himself/herself understood, and has provided informed consent.