Please select the eligibility criteria that correspond to the clinical trial below.
Title: Angioplasty and Stenting for Patients With Symptomatic Intracranial Atherosclerosis: Study Protocol of a Randomized Controlled Trial
Brief Summary: Background: Effectiveness of Percutaneous transluminal angioplasty and stenting (PTAS) on prevention of events of stroke and death in patients with symptomatic intracranial atherosclerosis (ICAS) is controversial.

Aim: to determine whether PTAS plus medical treatment (MT) are superior to MT alone in preventing events of stroke and death in patients with symptomatic ICAS.

Methods: The investigators will carry out a randomized controlled trial in 3 hospitals in China. A total of 198 patients with ICAS will be randomized into 2 groups: PTAS+MT and MT group. All patients will receive aspirin (100 mg daily) and clopidogrel (75 mg daily) immediately after randomization, and patients in PTAS+MT group will receive surgery within 5 days after randomization. The patients will be followed up for 1 year after randomization and assessed for events of stroke and death at 30 days and 1 year after randomization, the incidence of recurrent ischaemic stroke in the stenting-involved vascular territory at 30 days and 1 year after randomization, incidence of in-stent restenosis at 1 year after randomization,etc.


Options:
A: Inclusion Criteria:

* Patients aged from 18 to 70 years.
* Complaints of a Symptomatic ICAS: a history of recurrent transient ischemic attacks or an ischemic stroke within 1 year owing to a 70%-99% stenosis in an internal carotid artery, middle cerebral artery, vertebral artery, or basilar artery.
* A length ≤ 15mm of a stenosis in the target vessel and a vessel size \>2.5mm.
* Hypoperfusion in the territory of the target vessels, which is determined by CT or MRI in 14 days before stenting.
* CT or MRI scans show no massive cerebral infarction (beyond half of the territory of middle cerebral artery (MCA)), intracranial hemorrhage, epidural or sub-dural hemorrhage, and intracranial brain tumor.
* Patients who understand the purpose of the study and have provided informed consent.

Exclusion Criteria:

* Not able to receive general anesthesia.
* Not able to receive angiographic assessment.
* A stenosis \>50% in an extracranial carotid or vertebral artery on the ipsilateral side.
* Infarctions due to the perforators occlusion (determined by MRI scan), which is defined as basal ganglia or brainstem/thalamus infarction related with middle cerebral artery or basilar artery stenosis.
* A high risk (leading to a stroke or death) to deliver the stent to the lesion.
* A previous stent or angioplasty in the target lesion.
* Progressive neurological signs within 24 hours before enrolment
* Any haemorrhagic infarct within 14 days before enrolment
* The presence of a cardiac source of embolus
* Thrombolytic therapy within 24 hours before enrollment
* Presence of intraluminal thrombus proximal to or at the target lesion
* Myocardial infarction within previous 30 days
* Non-atherosclerotic lesions: arterial dissection, moya-moya disease; vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebrospinal fluid pleocytosis; radiation-induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process, and suspected recanalized embolus.
* Known contraindications for aspirin and clopidogrel treatment.
* An modified Rankin scale≥3.
* With a childbearing potential or a positive pregnancy test in 1 week before enrolment.
B: Inclusion criteria：

1. Eligible patients aged between 30-80 years; intracranial arterial stenosis related to the following non-atherosclerotic factors will be not be considered: arterial dissection, moya-moya disease; vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebrospinal fluid pleocytosis; radiation-induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process, and suspected recanalized embolus;
2. Symptomatic ICAS: presented with TIA or stroke within the past 12 months attributed to 70%-99% stenosis of a major intracranial artery (internal carotid artery, MCA \[M1\], vertebral artery, or basilar artery);
3. Degree of stenosis: 70%-99%; stenosis degree must be confirmed by catheter angiography for enrollment in the trial;
4. There might be remote infarctions on MRI scan, which could be accounted by the occlusion of the terminal cortical branches or hemodynamic compromise (perforator occlusion excluded). Infarction due to perforators occlusion is defined as basal ganglia or brainstem/thalamus infarction related with MCA or BA stenosis;
5. Expected ability to deliver the stent to the lesion;
6. All the patients should be performed with stenting beyond a duration of 3 weeks from the latest ischemic symptom onset;
7. No recent infarctions identified on MRI (indicated as high signals on DWI series) upon enrollment;
8. No massive cerebral infarction (\>1/2 MCA territory), intracranial hemorrhage, epidural or sub-dural hemorrhage, and intracranial brain tumor on CT or MRI scan;
9. mRS scale score of \<=2;
10. Target vessel reference diameter must be measured to be 2.00 mm to 4.50 mm; target area of stenosis is \<=14 mm in length;
11. No childbearing potential or has a negative pregnancy test within the past 1 week prior to study procedure; female patients had normal menses in the last 18 months;
12. Patient is willing and able to return for all follow-up visits required by the protocol;
13. Patients understand the purpose and requirements of the study and have signed informed consent form.

Exclusion criteria:

1. Refractory to general anesthesia; patients were not able to be overcome by pre-treatment with medical therapy.
2. Any condition that precludes proper angiographic assessment.
3. Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion.
4. Bilateral intracranial VA stenosis of 70%-99% and uncertainty about which lesion is symptomatic (e.g., if patient has pon, midbrain, temporal and occipital symptoms).
5. Presence of a previously placed intravascular stent or graft in the ipsilateral distribution within 30 days.
6. 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.
7. Severe vascular tortuosity or anatomy that would preclude the safe introduction of a guiding catheter, guiding sheath or stent placement.
8. Plan to perform concomitant angioplasty or stenting of an extracranial. vessel tandem to an ipsilateral intracranial stenosis.
9. Presence of intraluminal thrombus proximal to or at the target lesion.
10. Any aneurysm proximal to or distal to intracranial stenotic artery.
11. Intracranial tumors or any intracranial vascular malformations.
12. Computed tomographic or angiographic evidence of severe calcification at target lesion.
13. Thrombolytic therapy within 24 hours before enrollment.
14. Evolving stroke or progressive neurologic signs within 24 hours before enrollment.
15. Stroke of sufficient size (\>5cm on CT or MRI) to place patient at risk of hemorrhagic transformation during the procedure; hemorrhagic transformation of an ischemic stroke within the past 15 days.
16. Previous spontaneous intracerebral (parenchymal) or other intracranial (subarachnoid, subdural, or epidural) hemorrhage within 30 days.
17. Untreated chronic subdural hematoma \>5 mm in thickness.
18. Other cardiac sources of emboli such as left ventricular aneurysms, intracardiac filling defect, cardiomyopathy, aortic or mitral prosthetic heart valve, calcified aortic stenosis, endocarditis, mitral stenosis, atrial septal defect, atrial septal aneurysm, left atrial myxoma.
19. Myocardial infarction within previous 30 days.
20. Chronic atrial fibrillation; any episode of paroxysmal atrial fibrillation within the past 6 months, or history of paroxysmal atrial fibrillation requiring chronic anticoagulation.
21. Intolerance or allergic reaction to any of the medical therapy, including aspirin, clopidogrel, heparin, and local or general anesthetics.
22. History of life-threatening allergy to contrast medium. If not life-threatening and can be effectively pre-treated, patient can be enrolled at physicians' discretion.
23. Recent gastro-intestinal bleed that would interfere with anti-platelet therapy.
24. Active bleeding diathesis or coagulopathy; active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count \<125,000, hematocrit \<30, Hgb \<10 g/dl, uncorrected INR \>1.5, bleeding time \>1 minute beyond upper limit normal, or heparin-associated thrombocytopenia that increases the risk of bleeding, uncontrolled severe hypertension (systolic BP\>180 mm hg or diastolic BP\>115 mm hg), severe liver impairment (AST or ALT \>3 times normal, cirrhosis), creatinine \>265.2μmol/l (unless on dialysis)
25. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment.
26. Indication for warfarin or heparin beyond enrollment (note: exceptions allowed for use of systemic heparin during stenting procedure or subcutaneous heparin for deep venous thrombosis prophylaxis while hospitalized).
27. Inability to understand and cooperate with study procedures or sign informed consent
28. Severe dementia or psychiatric problems that prevent the patients from following an outpatient program reliably.
29. Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study
30. Actively participating in another drug or device trial that has not completed the required protocol follow-up period.
C: 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
D: INCLUSION:

Small subcortical ischemic stroke or subcortical TIA.

Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met:

* One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting \> 24 hrs within the past 6 months
* Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc.
* No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric.
* No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician.
* Subcortical TIA with corresponding lesion on DWI.
* MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(\<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote).

EXCLUSION:

To be eligible for entry into the study, the patient must not meet any of the criteria listed below:

* Disabling stroke (Modified Rankin Scale less than or equal to 4)
* Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
* Age under 30 years
* High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc)
* Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets
* Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA
* Prior ipsilateral carotid endarterectomy
* Impaired renal function: GFR \<40
* Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR)
* A score \< 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination
* Medical contraindication to MRI
* Pregnancy or women of child-bearing potential who are not following an effective method of contraception
* Geographic or social factors making study participation impractical
* Unable or unwilling to provide informed consent
* Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits
* Patients concurrently participating in another study with an investigational drug or device
* Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)

Answer: A