Please select the eligibility criteria that correspond to the clinical trial below.
Title: China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): a New, Prospective, Multi-center, Randomized Controlled Trial in China
Brief Summary: Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment, however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience, neither regarding natural history, nor treatment complications rate. As ICAS is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective randomized multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria.

The China Angioplasty \& Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial, is an ongoing, government-funded, prospective, multicenter randomized trial. It recruits patients with recent TIA or stroke caused by 70-99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume center with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days The CASSISS trial will be conducted in 8 sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 subjects (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by Dec, 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high volume centers.


Options:
A: All patients for whom treatment with the Wingspan Stent System is considered.
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:

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)
D: 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.

Answer: B