Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Concurrent Controlled Trial to Assess the Safety and Effectiveness of the Separator 3D as a Component of the Penumbra System in the Revascularization of Large Vessel Occlusion in Acute Ischemic Stroke
Brief Summary: This is a prospective, randomized, single blind, concurrent controlled, multi-center study. Patients presenting with symptoms of acute ischemic stroke who have evidence of a large vessel (2.5mm or greater in diameter) occlusion in the cerebral circulation will be assigned to either the Penumbra System with the Separator 3D or the Penumbra System without the Separator 3D. Each treated patient will be followed and assessed for 3 months after randomization. Up to 230 evaluable patients at up to 50 centers presenting with acute ischemic stroke in vessels accessible to the Penumbra Separator 3D System for revascularization within 8 hours of symptom onset. The hypothesis to be tested is that the safety and effectiveness of the Penumbra System with the Separator 3D for the revascularization of large vessel occlusion is not inferior to the Penumbra System alone.


Options:
A: Inclusion Criteria:

* From 18 to 85 years of age
* Present with symptoms consistent with an acute ischemic stroke for revascularization within 8 hours from symptom onset
* Refractory to or not eligible for IV rtPA therapy., e.g., presenting between 0 and 3 hours from symptom onset AND contraindicated for IV rtPA, or presenting between 3 and 8 hours of symptom onset, or evidence of persistent occlusion from vascular imaging after IV rtPA
* Evidence of a large vessel (2.5mm or greater in diameter) occlusion in the cerebral circulation
* NIH Stroke Scale (NIHSS) score 8 or more points
* Signed informed consent

Exclusion Criteria:

* History of stroke in the past 3 months.
* Females who are pregnant
* Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or higher
* Known severe allergy to contrast media
* Uncontrolled hypertension (defined as systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg)
* CT evidence of the following conditions at randomization:

  * Significant mass effect with midline shift
  * Large infarct region \>1/3 of the middle cerebral artery territory
  * Evidence of intracranial hemorrhage
* Angiographic evidence of an arterial stenosis proximal to the occlusion that could prevent thrombus removal
* Angiographic evidence of preexisting arterial injury
* Rapidly improving neurological status prior to enrollment
* Bilateral stroke
* Intracranial tumors
* Known history of cerebral aneurysm or arteriovenous malformation
* Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of \>1.7
* Baseline platelets \<50,000
* Use of IV heparin in the past 48 hours with PTT \>1.5 times the normalized ratio
* Baseline glucose \<50mg/dL or \>300mg/dL
* Life expectancy less than 90 days prior to stroke onset
* Participation in another clinical investigation that could confound the evaluation of the study device
B: Inclusion Criteria:

1. Age 18 - 80
2. Clinical signs consistent with acute ischemic stroke
3. Prestroke Modified Rankin Score ≤ 1
4. NIHSS ≥ 8 and \< 30 at the time of randomization
5. Initiation of IV t-PA within 4.5 hours of onset of stroke symptoms (onset time is defined as the last time when the patient was witnessed to be at baseline), with investigator verification that the subject has received / is receiving the correct IV t-PA dose for the estimated weight prior to randomization.
6. Thrombolysis in Cerebral Infarction (TICI) 0-1 flow in the intracranial internal carotid artery, M1 segment of the MCA, or carotid terminus confirmed by CT or MR angiography that is accessible to the Solitaire™ FR Device.
7. Subject is able to be treated within 6 hours of onset of stroke symptoms and within 1.5 hours (90 minutes) from CTA or MRA to groin puncture.
8. Subject is willing to conduct protocol-required follow-up visits.
9. An appropriate signed and dated Informed Consent Form (as allowed according to country regulations and approved by ethics committee and/or IRB) has been obtained
10. Subject is affiliated with a social security system (if required by individual country regulations).
11. Subject meets national regulatory criteria for clinical trial participation.

Exclusion Criteria:

1. Subject who is contraindicated to IV t-PA as per local national guidelines.
2. Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
3. As applicable by French law, subject who is a protected individual such as an incompetent adult or incarcerated person.
4. Rapid neurological improvement prior to study randomization suggesting resolution of signs/symptoms of stroke.
5. Known serious sensitivity to radiographic contrast agents.
6. Known sensitivity to Nickel, Titanium metals or their alloys.
7. Current participation in another investigational drug or device treatment study.
8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency. (A subject without history or suspicion of coagulopathy does not require INR or prothrombin time lab results to be available prior to enrollment.)
9. Renal Failure as defined by a serum creatinine \> 2.0 mg/dl (or 176.8 μmol/l) or Glomerular Filtration Rate \[GFR\] \< 30Warfarin therapy with INR greater than 1.7.
10. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
11. Life expectancy of less than 90 days.
12. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal.
13. Suspicion of aortic dissection.
14. Subject with a co-morbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
15. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day).
16. Known history of arterial tortuosity, pre-existing stent, and/or other arterial disease which would prevent the device from reaching the target vessel and/or preclude safe recovery of the device.

Imaging Exclusion Criteria:

1. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of hemorrhage on presentation.
2. CT or MRI evidence of mass effect or intra-cranial tumor (except small meningioma).
3. CT or MRI evidence of cerebral vasculitis.
4. CT showing hypodensity or MRI showing hyperintensity involving greater than 1/3 of the middle cerebral artery (MCA) territory (or in other territories, \>100 cc of tissue) on presentation.
5. Baseline non-contrast CT or DWI MRI evidence of a moderate/large core defined as extensive early ischemic changes of Alberta Stroke Program Early CT score (ASPECTS) \< 6.
6. CT or MRI evidence of a basilar artery (BA) occlusion or posterior cerebral artery (PCA) occlusion.
7. CTA or MRA evidence of carotid dissection or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy)
8. Imaging evidence that suggests, in the opinion of the investigator, the subject is not appropriate for mechanical thrombectomy intervention (e.g., inability to navigate to target lesion, moderate/large infarct with poor collateral circulation, etc).
C: Inclusion Criteria A. Clinical (Heterogeneous sampling frame)

1. Acute ischemic stroke
2. Age 18 or greater
3. Onset (last-seen-well) time to randomization time \< 12 hours.
4. Disabling stroke defined as a baseline NIHSS \> 5 at the time of randomization.
5. Pre-stroke (24 hours prior to stroke onset) independent functional status in activities of daily living with modified Barthel Index \> 90. Patient must be living in their own home, apartment or seniors lodge where no nursing care is required.

   B. Imaging (Homogeneous target population)
6. Confirmed symptomatic intracranial occlusion, based on single phase, multiphase or dynamic CTA, at one or more of the following locations: Carotid T/L, M1 MCA, or M1-MCA equivalent (2 or more M2-MCAs). Anterior temporal artery is not considered an M2.
7. Non-contrast CT and CTA for trial eligibility performed or repeated at ESCAPE stroke center with endovascular suite on-site.
8. Endovascular treatment intended to be initiated (groin puncture) within 60 minutes of baseline non-contrast CT with target baseline non-contrast CT to first recanalization of 90 minutes.
9. Signed informed consent or appropriate signed deferral of consent where approved.

Exclusion Criteria

1. Baseline non-contrast CT reveals a moderate/large core defined as extensive early ischemic changes of ASPECTS 0-5 in the territory of symptomatic intracranial occlusion.
2. Other confirmation of a moderate to large core defined one of three ways:

   1. On a single phase, multiphase or dynamic CTA: no or minimal collaterals in a region greater than 50% of the MCA territory when compared to pial filling on the contralateral side (multiphase/dynamic CTA preferred) OR
   2. On CT perfusion (\>8 cm coverage): a low CBV and very low CBF ASPECTS \<6 AND in the symptomatic MCA territory OR
   3. On CT perfusion(\<8 cm coverage): a region of low CBV and very low CBF \>1/3 of the CTP imaged symptomatic MCA territory.
3. Groin puncture is not possible within 60 minutes of the first slice of non-contrast CT acquisition (please note that if CTP is performed it should be done after CTA).
4. No femoral pulses or very difficult endovascular access that will result in a non-contrast CT-to-recanalization time that is longer than 90 minutes, or will result in an inability to deliver endovascular therapy.
5. Pregnancy; if a woman is of child-bearing potential a urine or serum beta HCG test is positive.
6. Severe contrast allergy or absolute contraindication to iodinated contrast.
7. Suspected intracranial dissection as a cause of stroke.
8. Clinical history, past imaging or clinical judgment suggests that the intracranial occlusion is chronic.
9. Patient has a severe or fatal comorbid illness that will prevent improvement or follow-up or that will render the procedure unlikely to benefit the patient.
D: Inclusion Criteria:

* Sudden focal neurological deficit attributable to a stroke
* Clearly defined time of onset, allowing initiation of intravenous treatment within 3 hours of symptoms onset and intra-arterial treatment within 6 hour of symptoms onset.
* Age greater than 18 years

Exclusion Criteria:

* Disability preceding stroke consistent with a modified Rankin scale score of 2-4
* Coma at onset
* Rapidly improving neurological deficit
* Seizure at onset
* Clinical presentation suggestive of a subarachnoid hemorrhage
* Previous history of intracranial hemorrhage
* Septic embolism
* Arterial puncture at a non compressible site within the previous 7 days
* Any traumatic brain injury within the previous 14 days
* Surgery of the central nervous system in the previous 3 months
* Gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 14 days.
* Current therapy with intravenous or subcutaneous heparin to rise the clotting time
* Known hereditary or acquired hemorrhagic diathesis, baseline INR greater than 1.5, aPTT more than 1.5 times normal, or baseline platelet count less than 100,000 per cubic millimeter
* Baseline blood glucose concentrations below 2.75 mm/L (50 mg/dL).
* Known contrast sensitivity.
* Women of childbearing potential (unless pregnancy impossible) or known to be breastfeeding. Uncontrolled hypertension defined by a blood pressure greater or equal 185 mmHg systolic or diastolic greater or equal 110 mm Hg in 3 separate occasions at least 10 minutes apart or requiring continuous IV therapy.
* Prognosis very poor regardless of therapy; likely to be dead within months.
* Unlikely to be available for follow-up (eg, no fixed home address, visitor from overseas).
* Any other condition which local investigators feels would pose a significant hazard in terms of risk/benefit to the patient, or if therapies are impracticable.

COMPUTED TOMOGRAPHIC (CT) SCAN EXCLUSION CRITERIA

* Intracranial tumors except small meningioma
* Hemorrhage of any degree
* Acute infarction (since this may be an indicator that the time of onset is uncorrected)

Answer: A