Tenecteplase versus alteplase before mechanical thrombectomy for acute large-vessel ischemic stroke

Efficacy and Safety of Tenecteplase Bridging Mechanical Thrombectomy for Acute Large Vessel Occlusive Stroke(TNK-LVO) :a Phase 3, Multicentre, Open-label, Randomised Controlled Trial

This trial tests whether tenecteplase given before mechanical thrombectomy helps adults with acute large-vessel ischemic stroke within 4.5 hours recover better than standard alteplase.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 850 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06658197 on ClinicalTrials.gov

What this trial studies

TNK-LVO is a phase III, multicenter, prospective, randomized, open-label, blinded-endpoint trial comparing intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg), each followed by mechanical thrombectomy for acute large-vessel occlusion stroke within 4.5 hours of last known well. Patients are randomized 1:1 at participating hospitals after imaging confirmation of occlusion in the ICA, M1/M2, ACA, PCA, or basilar artery and must have a prestroke mRS ≤2. The primary endpoint is functional independence (modified Rankin Scale ≤2) at 90 days, with blinded outcome adjudication. Safety monitoring includes imaging and hemorrhage assessments and protocol guidance to minimize delays to puncture and thrombectomy.

Who should consider this trial

Good fit: Adults aged 18 or older with an imaging-confirmed large-vessel occlusion who are eligible for IV thrombolysis and mechanical thrombectomy within 4.5 hours of last known well and have a prestroke mRS ≤2 are the intended participants.

Not a fit: Patients with hemorrhagic stroke, contraindications to contrast imaging, clinical coma (NIHSS item 1a = 3), those outside the 4.5-hour window, or without a large-vessel occlusion are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, tenecteplase could increase the chance of functional independence at 90 days, simplify pre-thrombectomy dosing with a single bolus, and improve reperfusion outcomes with comparable or lower bleeding risk.

How similar studies have performed: Earlier randomized and smaller trials, including EXTEND-IA TNK and pooled analyses, have shown promising or superior reperfusion and clinical outcomes with tenecteplase versus alteplase, but definitive large-scale confirmation is still needed.

Eligibility criteria

Inclusion Criteria:

1. Age is ≥18 years.
2. AIS symptom onset ≤4.5 hours, onset time refers to the time the patient was last known to be well. (Recommendation time from thrombolysis to puncture within 60 minutes).
3. Arterial occlusion of the internal carotid artery (ICA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), M1 or M2 segment of the middle cerebral artery (MCA), or basilar artery on computed tomography angiography (CTA) or magnetic resonance angiography (MRA).
4. Prestroke mRS score ≤2.
5. Informed consent from the patient or legally authorised representative.

Exclusion Criteria:

1. Patients diagnosed with hemorrhagic stroke (including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.) or other related conditions identified by CT.
2. Contraindication to imaging examinations involving contrast agent injection.
3. Patients presenting with clinical symptoms of coma (NIHSS Score Item 1a = 3).
4. History of intracranial hemorrhage.
5. History of severe head trauma or stroke within the past 3 months.
6. Intracranial or intraspinal surgery within the past 3 months.
7. Major surgery within the past 2 weeks.
8. Gastrointestinal or urinary tract bleeding within the past 3 weeks.
9. Intracranial tumor, arteriovenous malformation, or giant intracranial aneurysm.
10. Active visceral bleeding.
11. Aortic arch dissection.
12. Arterial puncture at a non-compressible site within the past week.
13. Uncontrolled hypertension despite active antihypertensive treatment: Systolic Blood Pressure \> 180 mmHg or Diastolic Blood Pressure \> 100 mmHg.
14. Acute hemorrhagic tendency, including platelet count \< 100 × 10⁹/L or other conditions.
15. Heparin treatment received within the past 24 hours.
16. For patients on oral anticoagulants: INR \> 1.7 or PT \> 15 seconds.
17. Use of direct thrombin inhibitors or direct Factor Xa inhibitors within the past 48 hours.
18. Blood glucose \< 2.8 mmol/L or \> 22.2 mmol/L.
19. Hypodensity affecting \> 1/3 of the middle cerebral artery territory or an equivalent proportion of the basilar artery territory on non-contrast CT.
20. Rapidly improving symptoms as determined by the investigator.
21. Participation as a subject in another research study within the past 30 days.
22. Any terminal illness where life expectancy is considered not to exceed 1 year.
23. Any condition where, in the judgment of the investigator, the study treatment might pose a risk to the patient or affect the patient's participation in the study.
24. Pregnant women.
25. Known allergy to the active ingredients (Alteplase, Tenecteplase) or any excipients.

Where this trial is running

Beijing, Beijing Municipality

• Xuanwu Hospital, Capital Medical University — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Xiuhai Guo, MD — Xuanwu Hospital, Beijing
• Study coordinator: Lu Wang, MD

Conditions: Stroke, Ischemic, Stroke, Acute, Thrombosis, Brain, Drug Effect, Ischemic stroke, Tenecteplase