The primary hypothesis being tested in this trial is that ischemic stroke patients in large vessel occlusion of anterior circulation at 4.5 - 9 hours post onset of stroke will have improved clinical outcomes when given endovascular thrombectomy with intravenous thrombolysis compared with that of given direct endovascular thrombectomy alone.

A number of multicenter randomized controlled trials have provided evidence supporting the application of endovascular therapy for acute ischemic stroke with anterior circulation large vessel occlusion. However, whether intravenous thrombolysis is necessary before endovascular therapy is still controversial. The combined trial data (including DEVT, DIRECT-MT, MR-CLEAN NO-IV and SKIP) assessing direct mechanical thrombectomy versus bridging therapy showed no difference in improving good functional outcome. However, a recent observational cohort study of 15832 patients treated with EVT, intravenous alteplase treatment was associated with better in-hospital survival and functional outcomes after adjusting for other covariates.

The 2019 AHA/ASA guidelines for the early management of patients with ischemic stroke states that mechanical thrombectomy is recommended for patients with anterior circulation large vessel occlusion within 6-24 hours of last known normal who meet the DWAN or DEFUSE-3 criteria (level I recommendation, level A evidence). The DEFUSE 3 perfusion-infarction core mismatch criteria is: core infarct volume <70mL, ischemic penumbra volume >15mL, and hypoperfusion volume/core infarct volume >1.8. Intravenous thrombolytic therapy is recommended for patients with ischemic stroke within 4.5 hours of onset. A meta-analysis of three randomized controlled trials recently published in the Lancet found that ischemic stroke at 4.5 to 9 hours of onset or wake stroke was consistent with a core infarct volume <70mL, a penumbra volume >10mL, and a hypoperfusion volume/core infarct volume >1.2. Benefit from intravenous thrombolytic therapy (3 month mRS 0-1 ratio, thrombolytic vs non-thrombolytic: 36% vs 29%). It was also strongly recommended by 2021 ESO guidelines on intravenous thrombolysis for acute ischemic stroke.

For these reasons the investigators hypothesize that endovacular thrombectomy bridging with intravenous thrombolysis is superior to direct thrombectomy in patients of stroke at 4.5 to 9 hours, guided with perfusion imaging.

Inclusion Criteria:

1. Patient/Legally Authorized Representative has signed the Informed Consent form
2. Age ≥ 18
3. Clinical signs consistent with an acute ischemic stroke
4. Neurological deficit with a NIHSS of ≥ 6 (deficits judged to be clearly disabling at presentation)
5. Patient is eligible for intravenous thrombolysis
6. Patient is eligible for endovascular treatment
7. Randomization no later than 8 hours 45 minutes after stroke symptom onset and initiation of IV t-PA must be started within 9 hours of stroke symptoms onset (for stroke with unknown time of onset, the midpoint of the time last known to be well and symptom recognition time)
8. ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA or CTA (including the reconstructed CTA derived from CTP). And target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml, mismatch ratio is >/= 1.8 and mismatch volume is >/= 15 ml)
9. Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6 based on baseline CT or MR imaging (MRI) (a region has to have diffusion abnormality in 20% or more of its volume to be considered MR-ASPECTS positive)

Exclusion Criteria:

1. Acute intracranial hemorrhage
2. Any contraindication for IV t-PA
3. Pre-treatment with IV t-PA
4. Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential.
5. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys
6. Known current participation in a clinical trial (investigational drug or medical device)
7. Renal insufficiency as defined by a serum creatinine > 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) < 30 mL/min or requirement for hemodialysis or peritoneal dialysis
8. Severe comorbid condition with life expectancy less than 90 days at baseline
9. Known advanced dementia or significant pre-stroke disability (mRS score of ≥2)
10. Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad)
11. Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments
12. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
13. Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT
14. Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
15. Radiological confirmed evidence of cerebral vasculitis
16. CTA or MRA evidence of carotid artery dissection
17. Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA