Drug Effect, Stroke, Acute, Stroke, Ischemic, Thrombosis, Brain
Conditions
Keywords
Ischemic stroke, Tenecteplase
Brief summary
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.
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.
Interventions
DRUGTenecteplase
Tenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg) plus mechanical thrombectomy
DRUGAlteplase
Alteplase 0.9 mg/kg administered as 10% bolus +90% infusion/1 hour (maximum dose 90mg) plus mechanical thrombectomy
Sponsors
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mRS ≤ 2 at 90 days or no change from baseline | 90 days from baseline | mRS ≤ 2 at 90 days or no change from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mTICI 2b/3 or absence of retrievable thrombus at initial angiogram | initial angiogram | mTICI 2b/3 or absence of retrievable thrombus at initial angiogram |
| mRS at 90 days from baseline | 90 days from baseline | mRS at 90 days from baseline |
| mRS 0-1 at 90 days or no change from baseline | 90 days from baseline | mRS 0-1 at 90 days or no change from baseline |
| Barthel index at 90 days from baseline | 90 days from baseline | Barthel index at 90 days from baseline |
| NIHSS reduce ≥ 8 or reaching 0-1 at 3 days from baseline | 3 days from baseline | NIHSS reduce ≥ 8 or reaching 0-1 at 3 days from baseline |
| Change of NIHSS at 1、3、7 days from baseline | 1、3、7 days from baseline | Change of NIHSS at 1、3、7 days from baseline |
Countries
China
Contacts
CONTACTLu Wang, MD
CONTACTXiuhai Guo, MD
PRINCIPAL_INVESTIGATORXiuhai Guo, MD
Xuanwu Hospital, Beijing
Outcome results
None listed