In patients with acute ischemic stroke secondary to large vessel occlusion, the role of intravenous adjunctive medications, such as tirofiban, or alteplase before endovascular thrombectomy has not been well investigated. This trial aim to evaluate the efficacy and safety of intravenous tirofiban versus alteplase for acute ischemic stroke patients with large vessel occlusion piror to endovascular thrombectomy.

Intravenous alteplase bridging with endovascular treatment (EVT) has been proven to be effective therapy in acute ischemic stroke patients due to large vessel occlusion (LVO). Several randomized controlled trials, aiming to explore the benefits and risks of intravenous alteplase prior to EVT in LVO stroke, have suggested that intravenous alteplase should not be omitted. Although intravenous alteplase results in successful reperfusion in approximately 10% to 20% of LVO patients, obviating the need for EVT, it has limitations. First, the time window for intravenous alteplase is narrow with strict indications and contraindications. Second, it may increase the risk of intracranial hemorrhage. Furthermore, alteplase is expensive. The above limitations lead to a very low proportion of patients who receive intravenous thrombolysis. Tirofiban is a selective IIb/IIIa receptor inhibitor, and it's effective in preventing thrombosis complications. Intravenous tirofiban has been increasingly used as an adjunctive treatment in acute ischemic stroke patients receiving EVT. However, a direct comparison between tirofiban and alteplase in LVO stroke has not been performed. We therefore conduct a randomized controlled trials to evaluate the efficacy and safety of intravenous tirofiban versus alteplase prior to EVT for acute ischemic stroke patients with LVO.

Inclusion Criteria:

1. Aged 18 years or older.

2. Presenting with acute ischemic stroke symptom.

3. Time from onset to hospital arrival:

   • (1) within 4.5 hours
   • (2) 4.5-9.0 hours, image inclusion criteria for the EXTEND trial must be met
   • (3) > 4.5 hours but within 24 hours, image inclusion criteria for the WAKE-UP trial must be met.

4. Eligible for intravenous thrombolysis.

5. Occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery, vertebrobasilar artery confirmed by CTA, MRA, or DSA.

6. Informed consent obtained from patients or their legal representatives.

Exclusion Criteria:

1. CT or MR evidence of hemorrhage (the presence of micro-bleeds is allowed);
2. Contraindications of IV rt-PA or tirofiban;
3. Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys;
4. Arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel;
5. Patients with a preexisting neurological or psychiatric disease that would confound the neurological functional evaluations;
6. CT or MRI evidence of mass effect or intracranial tumor (except small eningioma);
7. CT or MRI evidence of cerebral vasculitis;
8. CTA or MRA evidence of intracranial arteriovenous malformations or aneurysms;
9. Any terminal illness with life expectancy less than 6 months.

After the primary results was published