The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design. Patients with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be randomized 1:1 to 0.25mg/kg or 0.9 mg/kg alteplase before all participants undergo endovascular thrombectomy.

The study will be a multi-center, prospective, randomized, open- label, blinded endpoint (PROBE), controlled phase 3 trial (2 arm with 1:1 randomization) in ischemic stroke patients. Imagine is performed with CT or MRI acutely with imaging follow-up at 24-36 hours. The sample size is 1630.

Inclusion Criteria:

• 18≤Age≤80 years old;
• The clinical diagnosis was Acute ischemic stroke The time from onset to treatment was < 4.5h; The time at which symptoms begin is defined as "the time at which they finally appear normal";
• MRS before onset was ≤1 points;
• Baseline NIHSS (at the time of randomization) should be ≥5 and ≤25 points;
• Informed consent from the patient or surrogate.

Exclusion Criteria:

• Intracranial hemorrhage identified by CT or MRI (CMBs detected by SWI is not counted);
• Massive anterior cerebral infarction identified by CT or MRI (ASPECT < 6 or lesions larger than one third of the territory of the middle cerebral artery or with a volume larger than 70mL)
• Patients planning to receive endovascular therapy
• A history of severe CNS damage (such as aneurysm or arteriovenous malformation, craniocerebral trauma, intracranial or spinal cord surgery)
• Onset with seizures, and the paralysis was suspected to be related to Todd paralysis.
• Administration of heparin within 48 hours preceding the onset of stroke with a baseline APTT exceeding the upper limit of the normal range.
• Oral anticoagulant (such as warfarin) treatment with baseline INR>1.7 or PT>15 s;
• Administration of thrombin inhibitors or factor Xa inhibitors within 48 hours preceding the onset of stroke with abnormal coagulation parameters or platelet count;
• BP couldn't be controlled with aggressive treatment. Uncontrolled hypertension was defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, measured for three times every 10 minutes.
• Platelet count of less than 100×109/ L;
• Blood glucose <50 mg/dl (<2.8 mmol/L) or >400 mg/dl (22.22 mmol/L);
• History of intracranial hemorrhage or active hemorrhagic disease. (Such as gastrointestinal, urinary tract or retinal bleeding)
• Tumors with an increased risk of bleeding.
• Prolonged or traumatic cardiopulmonary resuscitation (>2 min), delivery within the last 10 days or recent puncture of non-compression vessels such as subclavian vein or jugular vein
• Acute pancreatitis or severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varicose veins, and active hepatitis;
• Aortic arch dissection;
• Major surgery or severe trauma in the past 2 weeks;
• Subjects had serious, fatal, or disabling disease with an expected survival of less than 3 months;
• Unable to complete neurological assessment and follow-up visits because of dementia or mental illness;
• Pregnant women, lactating women, or have positive pregnancy test;
• Allergy to tenecteplase or alteplase or their components;
• Participation in other clinical trials within 3 months prior to screening;
• Unsuitable to involve in this study or would result in increased risk, as judged by the investigators.