Please select the eligibility criteria that correspond to the clinical trial below.
Title: Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) Trial
Brief Summary: The purpose of the study is to understand whether a new treatment of stroke - endovascular clot removal - can be added to the current standard of care to improve patient outcomes.

All patients will receive the best standard stroke treatment. This includes treating patients with the clot dissolving drug tPA (tissue plasminogen activator). However, t-PA does not work in some patients and others are not eligible to receive t-PA because they present too late for treatment (they woke up with their stroke symptoms or their stroke was not witnessed).

During endovascular revascularization the blockage in the artery is removed with the use of devices called stentreivers and or by giving clot dissolving drug at the site of the blockage in the artery to restore blood flow. Stentrievers are devices that have been designed by different companies to remove blood clots from arteries.

Up to a maximum of 500 people at 20-25 hospitals across Canada and other countries will participate in this study.


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. Patients presenting with anterior circulation acute ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset
2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent
3. Patient"s age is ≥18 years
4. Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset.

   Imaging inclusion criteria

   Dual target:
5. Arterial occlusion on CTA or MRA of the ICA, M1 or M2
6. Mismatch - Using CT or MRI with a Tmax \>6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume. a) Mismatch ratio of greater than 1.2, and b) Absolute mismatch volume of greater than 10 ml, and. c) Infarct core lesion volume of less than 70mL

Exclusion Criteria:

1. Intracranial haemorrhage (ICH) identified by CT or MRI
2. Rapidly improving symptoms at the discretion of the investigator
3. Pre-stroke mRS score of ≥ 2 (indicating previous disability)
4. Inability to access the cerebral vasculature in the opinion of the neurointerventional team
5. Contra indication to imaging with MR with contrast agents
6. Participation in any investigational study in the previous 30 days
7. Any terminal illness such that patient would not be expected to survive more than 1 year
8. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
9. Pregnant women
10. Previous stroke within last three months
11. Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator.
12. Current use of oral anticoagulants and a prolonged prothrombin time (INR \> 1.6)
13. Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated partial thromboplastin time exceeding the upper limit of the local laboratory normal range.
14. Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Prior use of single or dual agent oral platelet inhibitors (clopidogrel and/or low-dose aspirin) is permitted.
15. Clinically significant hypoglycaemia.
16. Uncontrolled hypertension defined by a blood pressure \> 185 mmHg systolic or \>110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of "aggressive treatment" is left to the discretion of the responsible Investigator.
17. Hereditary or acquired haemorrhagic diathesis
18. Gastrointestinal or urinary bleeding within the preceding 21 days
19. Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.
20. Exposure to a thrombolytic agent within the previous 72 hrs
C: Inclusion Criteria:

* a clinical diagnosis of acute ischemic stroke,
* caused by a large vessel occlusion of the anterior circulation (distal intracranial carotid artery or middle M1/proximal M2) cerebral artery confirmed by CTA,
* CT or MRI ruling out intracranial hemorrhage,
* eligible for IVT and IAT (within 4.5 hours after symptom onset),
* a score of at least 2 on the NIH Stroke Scale,
* age of 18 years or older,
* written informed consent.

Exclusion Criteria:

* - Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, i.e. mRS \>2
* Any contra-indication for IVT, according to guidelines of the American Heart Association, i.e.:

  * arterial blood pressure exceeding 185/110 mmHg
  * blood glucose less than 2.7 or over 22.2 mmol/L
  * cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of recent infarction on neuro-imaging
  * serious head trauma in the previous 3 months
  * major surgery or serious trauma in the previous 2 weeks
  * gastrointestinal or urinary tract hemorrhage in the previous 3 weeks
  * previous intracerebral hemorrhage
  * use of anticoagulant with INR exceeding 1.7
  * known thrombocyte count less than 100 x 109/L
  * treatment with direct thrombin or factor X inhibitors
  * treatment with heparin (APTT exceeds the upper limit of normal value) in the previous 48 hours.
D: 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.

Answer: D