INtra-arterial AltEplase folloWing successfuL reperfusIoN After mEchanical Thrombectomy

The NEWLINE trial is a multicenter, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether adjunctive low-dose intra-arterial alteplase administered immediately after successful endovascular thrombectomy improves functional outcomes in adults with acute ischemic stroke due to anterior circulation large vessel occlusion. Eligible participants achieving successful reperfusion (eTICI 2b-3) within 24 hours of symptom onset will be randomized 1:1 to receive intra-arterial alteplase plus standard care or standard care alone. The primary outcome is excellent functional outcome (modified Rankin Scale score 0-1) at 90 days.

Inclusion Criteria: 1. Age ≥ 18 years old. 2. No significant pre-stroke functional disability (pre-stroke mRS 0-1) 3. Clinical diagnosis of acute ischemic stroke with anterior LVO 4. Time from symptom onset to randomization within 24 hours, including wake-up stroke or unwitness stroke; the onset time refers to "Last Known Well" (LKW). 5. Baseline NIHSS of 6 - 25 6. Non-contrast CT (NCCT) or diffusion-weighted imaging (DWI)-MRI Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. For patients with available perfusion imaging (CTP/MRP), additional criteria include: Ischemic core volume ≤ 70mL; Mismatch volume ≥ 15 ml; Mismatch ratio ≥ 1.8 7. Evidence of oclussion of the intracranial segment of the internal carotid artery (ICA), or M1 or M2 segment of the middle cerebral artery (MCA) on CT angiography (CTA) or MR angiography (MRA) 8. Treated with EVT resulting eTICI score of 2b-3. Patients with an eTICI score of 2b-3 on the diagnostic cerebral angiography before MT are also eligible for the study. 9. Informed consent obtained from patient or acceptable patient surrogate. Exclusion Criteria: 1. mRS score ≥ 2 before stroke onset 2. Anticipated advanced comorbid disease with life expectancy \< 12 months 3. Acute head trauma 4. Severe hypertension with SBP \> 185 mmHg or DBP \> 110 mmHg and refractory to treatment. 5. Any active or recent major bleeding (gastrointestinal, urinary tract bleeding, etc.) in the last 30 days. 6. Contraindication to recombinant human tissue plasminogen activator (rt-PA) (except time to therapy). 7. Women who are pregnant at stroke onset. 8. Recent intracranial surgery in the past 30 days. 9. Known genetic or acquired bleeding disposition with anticoagulation factor deficiency. 10. Coagulation disorder with INR \> 1.7 or use of new oral anticoagulants (within 48 hours of symptom onset). 11. Platelet count \< 50 G/L. 12. Blood glucose \< 2,8 mmol/L (50 mg/dl) or \> 22,2 mmol/L (400 mg/dl) 13. Known severe renal insufficiency with glomerular filtration rate \< 30 ml/min or blood creatinine \> 220 µmol/L (2,5 mg/dl). 14. Requiring hemodialysis or peritoneal dialysis 15. Suspected vascular occlusion as a result of infective endocarditis 16. Suspected cerebral vasculitis based on medical history and/or angiographic evaluation. 17. Suspected aortic dissection 18. Severe allergy to contrast (non-mild rash allergy) or absolute contraindication to iodine contrast, heparin. 19. Acute ischemic stroke with significant mass effect or evidence of midline shift on baseline neuroimaging, or clinical signs of brain herniation 20. Suspected acute ischemic stroke involving multiple vascular territories or occlusion of two or more distinct vascular systems on neuroimaging 21. Evidence of intracranial hemorrhage (including hemorrhagic transformation) on neuroimaging 22. Brain tumor (with significant mass effect) 23. Stent placement and other situations during the EVT procedure that requires antiplatelet therapy or anti coagulation within the first 24 hours. 24. Extracranial segment occlusion of the ICA and post-procedural etiology suggests vascular dissection. 25. Intravenous heparin administration (however, heparinised saline flushes are allowed) 26. Procedure time \> 90 min 27. Number of thrombectomy passes \> 5 28. Complications occur during EVT: Vascular rupture, dissection, or contrast extravasation 29. Complete clinical recovery after rapid recanalization. 30. Participation in other interventional randomized clinical trials that may confound the outcome assessment of the study. 31. Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment). 32. Unlikely to be available for 90-day follow-up