Randomization of Endovascular Treatment in Acute Ischemic Stroke in the Extended Time Window
Randomization of Endovascular Treatment in Acute Ischemic Stroke in the Extended Time Window
A phase III, randomized, multi-center, open label clinical trial that will examine whether
 endovascular treatment is superior to standard medical therapy alone in patients who suffer a
 large vessel anterior circulation ischemic stroke within 8-24 hours from time last seen well
Prospective, multi-center, randomized, controlled, open-label, blinded-endpoint trial with a
 sequential design. The randomization employs a 1:1 ratio of mechanical thrombectomy with
 stent-retriever and/or thromboaspiration versus medical management alone in patients who
 suffer a large vessel anterior circulation ischemic stroke between 8 and 24 hours from time
 last seen well. Randomization will be done under a minimization process using age (≤68 vs.
 >68 years), baseline NIHSS (<17 v. ≥17), ASPECTS (5-7 vs. 8-10), therapeutic window (6-12 or
 12-24 hours after TLKW), occlusion site (Intracranial ICA or M1), and clinical site. For the
 primary endpoint, subjects will be followed for 90 days post-randomization. Sham endovascular
 procedure has been rejected due to the medical risk of the angiography and practical issues
 that difficult to maintain blindness of investigators.
Inclusion Criteria:

 1. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment or the
 treatment is contraindicated (e.g., subject presents beyond recommended time from
 symptom onset), or where patient has received IV thrombolytic therapy without clinical
 improvement.

 2. No significant pre-stroke functional disability (mRS ≤2)

 3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 8
 points (assessed within one hour prior to qualifying imaging)

 4. Age ≥18 years (no upper age limit)

 5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions) and/or
 MCA-M1 segment suitable for endovascular treatment, as evidenced by CTA, MRA or
 angiogram, with or without concomitant cervical carotid occlusion or stenosis.

 6. The presence of Age-Adjusted modified Clinical ASPECTS Mismatch (mCAM) defined as
 ASPECTS 5-10 and one of the following criteria:

 1. NIHSS ≥ 8 and >50% involvement in 0-1 Cortical (e.g. M1-6) ASPECTS areas (any
 age);

 2. NIHSS ≥ 8 and >50% involvement in 0-2 Cortical (e.g. M1-6) ASPECTS areas (and age
 < 80 years old);

 3. NIHSS ≥ 15 and >50% involvement in 0-3 Cortical (e.g. M1-6) ASPECTS areas (and
 age < 80 years old).

 7. Patient treatable within 6-24 hours of symptom onset. Symptoms onset is defined as
 point in time the patient was last seen well (at baseline). Treatment start is defined
 as arterial puncture.

 8. Informed consent obtained from patient or acceptable patient surrogate

 Exclusion Criteria:

 -Clinical criteria

 1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant
 therapy with INR > 3.0

 2. Baseline platelet count < 30.000/µL

 3. Baseline blood glucose of < 50mg/dL

 4. Severe, sustained hypertension (SBP > 185 mm Hg or DBP > 110 mm Hg) NOTE: If the blood
 pressure can be successfully reduced and maintained at the acceptable level using AHA
 guidelines recommended medication (including iv antihypertensive drips), the patient
 can be enrolled.

 5. Patients in coma defined as totally unresponsive; responding only with reflexes or
 being areflexic (Intubated patients for transfer could be randomized only in case an
 NIHSS is obtained by a neurologist prior transportation).

 6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS

 7. Serious, advanced, or terminal illness with anticipated life expectancy of less than
 one year.

 8. History of life-threatening allergy (more than rash) to contrast medium

 9. Subjects who has received IV t-PA treatment beyond 4.5 hours from the beginning of the
 symptoms

 10. Woman of childbearing potential who is known to be pregnant or who has a positive
 pregnancy test on admission.

 11. Subject participating in a study involving an investigational drug or device that
 would impact this study.

 12. Cerebral vasculitis

 13. Patients with a pre-existing neurological or psychiatric disease that would confound
 the neurological or functional evaluations, mRS score at baseline must be ≤2. This
 excludes patients who are severely demented, require constant assistance in a nursing
 home type setting or who live at home but are not fully independent in activities of
 daily living (toileting, dressing, eating, cooking and preparing meals, etc.)

 14. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor
 from overseas).

 - Neuroimaging criteria

 15. Hypodensity on CT or restricted diffusion on MRI amounting to an ASPECTS score of <5.

 16. Complete involvement of more than 3 cortical ASPECTS areas (e.g. M1, M2, M3, M4, M5,
 or M6).

 17. Complete absence of leptomeningeal collaterals on CT angiography (e.g. Malignant CTA
 pattern or score 0).

 18. CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed).

 19. Significant mass effect with midline shift.

 20. Evidence of ipsilateral carotid occlusion, high grade stenosis or arterial dissection
 in the extracranial or petrous segment of the internal carotid artery that cannot be
 treated or will prevent access to the intracranial clot or excessive tortuosity of
 cervical vessels precluding device delivery/deployment

 21. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior
 circulation, or anterior/posterior circulation)

 22. Evidence of intracranial tumor (except small meningioma).