Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2)

Inclusion Criteria: * Age ≥ 18 year; * Acute ischemic stroke presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received standard-dose intravenous thrombolysis, and with no planned thrombectomy; * Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4; * Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI); * No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis; * Follow-up imaging (CTA or MRA) at 1 hour after the first thrombolysis rules out intracranial hemorrhage and confirms the presence of large or medium vessel occlusion (internal carotid artery, M1-M3 segments of the middle cerebral artery, A1-A3 segments of the anterior cerebral artery, P1-P3 segments of the posterior cerebral artery, basilar artery or V4 segment of the vertebral artery, PICA, AICA, or SCA); * The second intravenous thrombolysis can be administered within 6 hours of onset; * First stroke onset or past stroke without obvious neurological deficit (mRS≤1); * Signed informed consent. Exclusion Criteria: * Planed for endovascular treatment; * Significant white matter hyperintensities (Fazekas score 3); * Any coagulation abnormality before the first thrombolysis, including INR \> 1.5; * Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.； * Pregnancy； * Allergy to the investigational drug(s)； * Comorbidity with other serious diseases; * Participating in other clinical trials within 3 months; * Patients not suitable for the study considered by researcher.