Efficacy and Safety of Tenecteplase Bridging Mechanical Thrombectomy for Acute Large Vessel Occlusion Stroke (TNK-LVO)

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

A phase III, multicentre, prospective, randomised, open-label, blinded-endpoint clinical trial will evaluate two thrombolytic agents for the treatment of acute large vessel occlusion stroke within 4.5 hours from symptoms onset: intravenous tenecteplase bridging mechanical thrombectomy vs. intravenous alteplase bridging mechanical thrombectomy.

Study Overview

• Status: Recruiting
• Conditions: Drug Effect; Stroke, Ischemic; Stroke, Acute; Thrombosis, Brain
• Intervention / Treatment: Drug: Tenecteplase; Drug: Alteplase

Detailed Description

Efficacy and Safety of Tenecteplase Bridging Mechanical Thrombectomy for Acute Large Vessel Occlusive Stroke(TNK-LVO) is a phase III, multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial. Randomization will be 1:1 according to reperfusion treatment modalities: (A) Intravenous thrombolysis with tenecteplase (0.25 mg/kg) plus mechanical thrombectomy vs. (B) Intravenous thrombolysis with alteplase (0.9 mg/kg) plus mechanical thrombectomy. For the primary outcome, the subjects will be followed up within 90 days after randomization. The primary outcome will be the Functional independence defined as modified Rankin Score ≤ 2.

• Study Type: Interventional
• Enrollment (Estimated): 850
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lu Wang, MD; Phone Number: 13161090533; Email: wanglu3261999@163.com
• Study Contact Backup: Name: Xiuhai Guo, MD; Phone Number: 18810285127; Email: guoxhxuan@126.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100053
      • Recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Xiuhai Guo, MD, PhD; Phone Number: 86-10-83198852; Email: guoxhxuan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tenecteplase; Subjects assigned to this arm will receive an intravenous bolus of 0.25mg/kg tenecteplase before the mechanical thrombectomy.	Drug: Tenecteplase; Tenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg) plus mechanical thrombectomy; Other Names: TNK
Active Comparator: alteplase; Subjects assigned to this arm will receive an intravenous 0.9 mg/kg alteplase(10% bolus +90% infusion/1 hour) before the mechanical thrombectomy.	Drug: Alteplase; Alteplase 0.9 mg/kg administered as 10% bolus +90% infusion/1 hour (maximum dose 90mg) plus mechanical thrombectomy; Other Names: recombinant tissue plasminogen activator (rtPA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS ≤ 2 at 90 days or no change from baseline	mRS ≤ 2 at 90 days or no change from baseline	90 days from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mTICI 2b/3 or absence of retrievable thrombus at initial angiogram	mTICI 2b/3 or absence of retrievable thrombus at initial angiogram	initial angiogram
mRS at 90 days from baseline	mRS at 90 days from baseline	90 days from baseline
mRS 0-1 at 90 days or no change from baseline	mRS 0-1 at 90 days or no change from baseline	90 days from baseline
Barthel index at 90 days from baseline	Barthel index at 90 days from baseline	90 days from baseline
NIHSS reduce ≥ 8 or reaching 0-1 at 3 days from baseline	NIHSS reduce ≥ 8 or reaching 0-1 at 3 days from baseline	3 days from baseline
Change of NIHSS at 1、3、7 days from baseline	Change of NIHSS at 1、3、7 days from baseline	1、3、7 days from baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
sICH within 36 hours from baseline	Defined by Safe Implementation of Thrombolysis in Stroke and The European Cooperative Acute Stroke Study III	36 hours from baseline
Vascular death within 90 days from baseline	Death from stroke, heart attack or pulmonary embolism	Within 90 days from baseline
Death from any cause within 90 days from baseline	Death from any cause within 90 days from baseline	Within 90 days from baseline
SAEs within 90 days from baseline	Severe adverse events within 90 days from baseline	Within 90 days from baseline

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Xiuhai Guo, MD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Ischemic stroke; Tenecteplase
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Intracranial Embolism and Thrombosis; Thromboembolism; Ischemic Stroke; Stroke; Intracranial Thrombosis; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tenecteplase; Tissue Plasminogen Activator
• Other Study ID Numbers: [2024]288-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No