Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intra-arterial Thrombectomy as an Acute Treatment Intervention for Stoke: the Endovascular Acute Stoke Intervention (EASI) Trial
Brief Summary: Stroke constitutes the primary cause of acquired disability in adults and the second cause of dementia following Alzheimer disease. It has been shown that patients with a moderate to severe clinical score have occlusion of brain large vessels, resulting in a worse clinical outcome. Many studies have demonstrated that early recanalization after IV rtPA is more restricted, the larger and more proximal the artery. Several systems for mechanical intracranial arterial thrombectomy of large trunks have recently been proposed and are now available. Potential advantages of these mechanical systems on chemical thrombolysis are speed (a few minutes versus 1 hour) and absence of thrombolytic injection.

The objective of the EASI trial is thus to:

* To validate intra-arterial thrombectomy use during the acute phase of cerebral stroke in patients treated with IV thrombolysis or in patients for whom thrombolysis is contra-indicated.
* To determine whether a combined approach, standard treatment plus thrombectomy, is superior to standard treatment alone within 5 h of the appearance of symptoms, in patients with occlusion of proximal cerebral arteries following moderate to severe stroke (NIHSS larger than or equal to 8), evaluated at 3 months.

The design is a randomized, controlled multicentric trial, with a parallel comparison between standard and combined (standard plus thrombectomy) treatment.

480 patients fulfilling eligibility criteria will be sufficient to demonstrate the primary hypothesis of a 15% difference in number of subjects with a favorable mRS (less than or equal to 2) at 3 months, with the assumption of a 25% efficacy for IV thrombolytic treatment at 3 months.

IV thrombolysis is carried out according to standard practice. Mechanical thrombectomy is carried out with already approved devices, according to the manufacturer's instructions, following a diagnostic cerebral angiography.

The primary efficacy endpoint is clinical: favorable mRS (less than or equal to 2) at 3 months.

The primary safety endpoint is rate of death at 3 months and rate of symptomatic hemorrhage at 24 hours.

If the primary hypothesis is validated, expected benefits of this study is a higher rate of autonomy for stroke patients with all the attendant consequences: reduction in hospital stays, and a faster return to the activities of daily life.


Options:
A: 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
B: Inclusion Criteria:Subjects will be eligible if the following criteria are met:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study.
* Age \> 18 years
* NIHSS ≥ 4 or isolated aphasia or isolated hemianopsia

Exclusion Criteria:

* NIHSS \>30
* Coma
* Rapidly improving symptoms
* History of stroke in the last 6 weeks
* Seizure at onset
* Subarachnoid Hemorrhage (SAH ) or suspected SAH
* Any history of Intracrannial Hemorrhage (ICH)
* Neoplasm
* Septic embolism
* Surgery, biopsy, trauma or LP in last 30 days
* Head trauma in the last 90 days
* Bleeding diathesis, or INR \>1.7 or PTT \>1.5 times baseline or platelet \<100K
* SBP \>180 or DBP ≥100 despite treatment with 3 doses of IV Labetalol (10-20 mg Q10")
* Lacunar stroke syndrome
* CT: Hemorrhage, tumor (except small meningioma), significant mass effect, midline shift, acute hypodensity or \>1/3 MCA territory sulcal effacement
* Radiological contrast hypersensitivity
* Angiographic: Dissection, lack of access, lack of occlusion, or nonatherosclerotic arteriopathy
C: Inclusion Criteria:

* Age greater than or equal to 18
* NIHSS greater than or equal to 8
* onset of symptoms is less than 5 hours OR symptom/imaging mismatch
* suspected occlusion of the M1 or M2 segment of the MCA, supraclinoid ICA, or basilar trunk.

Exclusion Criteria:

* established infarction of the target symptomatic territory
* co-morbid diseases which suggest a poor 90 day outcome irrespective of management
* radiologic evidence of hemorrhagic transformation of the infarcted territory
D: Inclusion Criteria:

* Clinical diagnosis of supratentorial acute ischaemic stroke
* Male or nonpregnant female ≥18 years of age
* Clinically significant neurological deficit and NIHSS score ≥6.
* Eligible for IV rtPA according to standard guidelines and able to be commenced on IV treatment \<4.5h after symptom onset.
* Enrolment, randomisation and procedure commencement (groin puncture) possible within 90 minutes of the start of IV rtPA treatment (groin puncture maximum 5.5h after stroke onset).
* Occlusion of the main middle cerebral artery (MCA) trunk, MCA bifurcation or intracranial internal carotid artery(carotidT, M1 or single proximal M2 branch) demonstrated on CTA, MRA, or DSA.
* Interventional device delivery (guide catheter placed beyond aortic arch and angio obtained) can be achieved within 6 hours of onset of the stroke.
* Consent of patient or representative.
* Independent prior to the stroke (estimated mRS 02)
* Expected to be able to be followed up at 3 months

Exclusion Criteria:

* CT evidence of intracranial haemorrhage, or evidence of extensive established hypodensity on CT.
* Clinical history suggestive of subarachnoid haemorrhage even if CT normal.
* Known vascular access contraindications e.g. femoral bypass surgery, tight ipsilateral carotid stenosis, unsuitable proximal vascular anatomy likely to render endovascular catheterisation difficult or impossible.
* Extracranial ICA occlusion or basilar artery occlusion
* Alternative intracranial pathology potentially responsible for the new symptoms
* Medical comorbidities which would preclude safe cerebral vessel catheterisation or which are expected to limit life expectancy to \<3 months (eg severe cardiac, renal or hepatic failure, significant coagulopathy, metastatic malignancy)
* Known allergy to radiological contrast

Answer: C