Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-Ⅲ）

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.

Eligibility Criteria:
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.