Randomization to Endovascular Treatment Alone or Preceded by Systemic Thrombolysis With Tenecteplase in Ischemic Stroke

Inclusion Criteria:

• Acute ischemic stroke where a patient is eligible for IV thrombolytic treatmentwithin 4.5 hours of stroke onset.

• No significant pre-stroke functional disability (mRS ≤ 1)

• Baseline NIHSS scores obtained before randomization must be equal to or higher than 6 points

• Age equal ≥ 18 and =< 85 years

• Occlusion (TICI 0-1) of the ICA or proximal MCA segments (M1 or M2) suitable forendovascular treatment, as evidenced by CTA, MRA, or angiogram, with or withoutconcomitant cervical carotid stenosis or occlusion.

• Patient randomized within 4.5 hours of symptom onset. Symptoms onset is defined asthe point in time the patient was last seen well (at baseline). Treatment start isdefined as groin puncture, max 90 minutes after randomization.

• Patients who have woken up with the symptoms and who have a mismatch FLAIR-DWIaccording to the WAKE-UP Trial will be considered as having a time window of <4.5h.

• Informed consent obtained from the patient or acceptable patient surrogate.

Exclusion Criteria:

• Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulanttherapy with INR > 1.7 or direct oral anticoagulants such as thrombin antagonists (ex: dabigatran) or X factor (ex: rivaroxaban, apixaban, edoxaban) at the least 48hours.

• Baseline platelet count < 100.000/μL

• Baseline blood glucose of < 50mg/dL or > 400mg/dl

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

• Patients in coma (NIHSS item of consciousness >1) (Intubated patients for transfercould be randomized only in case an NIHSS is obtained by a neurologist priortransportation).

• Seizures at stroke onset which would preclude obtaining a baseline NIHSS

• Serious, advanced, or terminal illness with anticipated life expectancy of less thanone year.

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

• Subjects who has received IV t-PA treatment before the randomization.

• Renal failure with serum creatinine ≥ 3 mg/dl

• Woman of childbearing potential who is known to be pregnant or who has a positivepregnancy test on admission.

• Subject participating in a study involving an investigational drug or device thatwould impact this study.

• Cerebral vasculitis, endocarditis or subarachnoid hemorrhage.

• Patients with a pre-existing neurological or psychiatric disease that would confoundthe neurological or functional evaluations.

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

• Hypodensity on CT more than one third of MCA territory or hypersignal in more thanone third of MCA territory on MR-DWI.

• ASPECTS score < 6 (no contrast at least 5 mm cut imaging on CT) or on MR-DWIsequence.

• CT or MR evidence of hemorrhage (the presence of < 5 GRE, SWI, SWAN microbleeds isallowed).

• Significant mass effect with midline shift.

• Evidence of ipsilateral carotid occlusion, high grade stenosis or arterialdissection in the extracranial or petrous segment of the internal carotid arterythat cannot be treated or will prevent access to the intracranial clot or excessivetortuosity of cervical vessels precluding device delivery/deployment.

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

• Evidence of intracranial tumor (except small meningioma).