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.