Despite being the standard pharmacological reperfusion therapy for acute ischemic stroke, intravenous thrombolysis is limited by suboptimal recanalization rates. Tenecteplase (TNK), a newer thrombolytic agent, offers practical advantages over alteplase, including single bolus administration. However, a significant proportion of patients fail to achieve early clinical improvement after standard thrombolysis, likely due to persistent vessel occlusion.

This study proposes to investigate a rescue strategy for patients who do not show significant neurological improvement within one hour after receiving standard intravenous tenecteplase within 3 hours of stroke onset. The primary objective is to evaluate the safety and feasibility of administering a second dose of tenecteplase in this scenario. The study will also explore the potential efficacy of this approach in improving recanalization and functional outcomes.

Inclusion Criteria:

• Age ≥ 18 year;
• Acute ischemic stroke within 3 hours of onset, having received standard intravenous thrombolysis;
• Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
• No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis, with intracranial hemorrhage ruled out by neuroimaging;
• The second intravenous thrombolysis can be administered within 4.5 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 cerebral white matter hyperintensities (Fazekas score 3)；
• Any coagulation abnormality before the first thrombolysis, including INR > 1.5；
• Pregnancy；
• Allergy to the investigational drug(s)；
• Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis;
• Comorbidity with other serious diseases;
• Participating in other clinical trials within 3 months;
• Patients not suitable for the study considered by researcher.