Stroke
Conditions
Keywords
acute ischemic stroke, large vessel occlusion, thrombolysis, tenecteplase, dosage, computed tomography, magnetic resonance imaging, diffusion weighted imaging, early combined imaging outcomes, modified Rankin scale, time window beyond 4.5 hours
Brief summary
To explore the efficacy and safety of tenecteplase for acute ischemic stroke patients (onset time 4.5-24h) of large vessel occlusion using early combined CT/MR imaging outcomes
Interventions
DRUGTenecteplase
Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
DRUGThe best treatment selected by local doctors(Aspirin, Recombinant Tissue Plasminogen Activator, Urokinase, Thrombectomy)
Best treatment arm
Sponsors
Puer People's Hospital
Shanghai 6th People's Hospital
Hexigten Traditional Chinese and Mongolian Medicine Hospital
Yangpu Hospital, School of Medicine, Tongji University
The First Affiliated Hospital of Shanxi Medical University
Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine
Linyi People's Hospital
Shanghai 10th People's Hospital
Nanshi Hospital of Nanyang
Fudan University
Xuzhou Medical University Affiliated Hospital of Huaian
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
The First Affiliated Hospital of Soochow Medical University
Affiliated Haian People's Hospital of Nantong University
First Affiliated Hospital of Harbin Medical University
the Third Hospital of Mianyang
Zhejiang Province People's Hospital
Shanghai East Hospital
The Central Hospital of Jiaozuo Coal Group
Huizhou Municipal Central Hospital
Zhejiang University
The Second Affiliated Hospital of Chongqing Medical University
Ningbo No. 1 Hospital
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients presenting with anterior circulation acute ischaemic stroke 2. Time from onset to treatment 4.5h-24h 3. Patient's age is \>= 18 years，\<= 80 4. Pre-stroke mRS score of \<= 2 5. Clinically significant acute neurologic deficit 6. Baseline National Institute of Health stroke scale \>= 6 7. Vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on computed tomography angiography (CTA)/MRA 8. Multimodal CT/magnetic resonance imaging: perfusion lesion volume (DT \> 3 s) to infarct core volume ratio (rCBF\<30% or diffusion-weighted imaging lesion) \>1.2, absolute difference \>10 ml, and ischemic core volume \<70ml 9. Informed consent was obtained from patients.
Exclusion criteria
1. Intracranial hemorrhage or subarachnoid hemorrhage identified by CT or MRI 2. Rapidly improving symptoms (patient with an NIHSS score decrease to \< 4 at randomization) 3. Pre-stroke mRS score of \> 2 4. Contraindication to imaging with CT/magnetic resonance imaging with contrast agents 5. Infarct core \>1/3 middle cerebral artery (MCA) territory 6. Platelet count \< 100x10\^9/L 7. Symptoms were caused by low blood glucose \< 2.7 mmol/l 8. Severe uncontrolled hypertension, i.e. systolic blood pressure \>= 180 mmHg or diastolic blood pressure \>=100 mmHg 9. Current use of warfarin with a prolonged prothrombin time (INR \> 1.7 or prothrombin time \> 15s) 10. Use of low molecular weight heparin within 24 hours 11. Use of non-vitamin K antagonist oral anticoagulants (NOACs) within 48 hours 12. Use of glycoprotein IIb - IIIa inhibitors within 72 hours. 13. Arterial puncture at noncompressible site in previous 7 days 14. Major surgery in previous 14 days which poses risk in the opinion of the investigator 15. Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days) 16. Significant head trauma or prior stroke in previous 3 months 17. History of previous intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Risks were considered by the investigator 18. Hereditary or acquired haemorrhagic diathesis 19. Active internal bleeding 20. Symptoms suggestive or recent acute pancreatitis, active gastrointestinal ulcer 21. Severe liver disease, including liver failure, cirrhosis, portal hypertension and active hepatitis 22. Pregnancy or lactation 23. Various dying diseases with life expectancy ≤3 months 24. Other conditions in which doctors believe that participating in this study may be harmful to the patient 25. Patients participated in any trial in 30 days 26. Allergic to the test drug and its ingredients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| patients without endovascular therapy obtained >50% reperfusion at 4-6 hours | 4-6 hours | Without endovascular therapy: \>50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours |
| patients with endovascular therapy: mTICI score 2b or better at initial angiogram | Before endovascular therapy | With endovascular therapy: mTICI score 2b or better at initial angiogram after thrombolysis before endovascular therapy |
| no symptomatic intracranial hemorrhage at 24-36 hours | 24-36 hours | No symptomatic intracranial hemorrhage at 24-36 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical efficacy outcome: percent of excellent functional outcome (modified Rankin scale 0-1) at 90 days (plus or minus 7 days) | 90 days (plus or minus 7 days) | percent of excellent functional outcome (modified Rankin scale 0-1) at 90 days (plus or minus 7 days) |
| Clinical efficacy outcome: percent of good functional outcome (modified Rankin scale 0-2) at 90 days (plus or minus 7 days) | 90 days (plus or minus 7 days) | percent of good functional outcome (modified Rankin scale 0-2) at 90 days (plus or minus 7 days) |
| Clinical efficacy outcome: incident event | 90 days (plus or minus 7 days) | Incident vascular event within 90 days (ischemic stroke/ hemorrhagic stroke/ cardiac infarct/ cardiac or brain revascularization (including Carotid Endarterectomy, Intracranial and Extracranial Artery Intervention, Intracranial and extracranial artery bypass, and Coronary artery intervention or bypass graft)) |
| Imaging safety outcome: Intracranial hemorrhage of any volume at 24-36 hours | 24-36 hours | Intracranial hemorrhage of any volume at 24-36 hours |
| Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours | 24-36 hours | Parenchymal hematoma 2 at 24-36 hours |
| Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours | 24-36 hours | Symptomatic intracranial hemorrhage at 24-36 hours |
| Clinical safety outcome: death within 90 days | 90 days (plus or minus 7 days) | Death within 90 days (plus or minus 7 days) |
| Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography | 4-6 hours | Recanalization rate on CTA/MRA at 4-6 hours |
| Barthel index | 90 days (plus or minus 7 days) | Barthel index at 90 days (plus or minus 7 days). The Barthel Index is a scale that indicates the ability to perform a selection of activities of daily living. It comprises 10 items (tasks), with total scores ranging from 0 (worst mobility in activities of daily living) to 100 (full mobility in activities of daily living) and it has adequate clinimetric (quality of clinical measurements) properties in stroke rehabilitation. In the index, the 10 items have these scoring combinations: a) 0 and 5, b) 0, 5 and 10, or c) 0, 5, 10 and 15. These items in the Barthel Index address a patient's ability in feeding, bathing, grooming, dressing, bowel and bladder control, toileting, chair transfer, ambulation and stair climbing. |
| Imaging efficacy outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours | 4-6 hours | Without endovascular therapy: \>50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours without Parenchymal hematoma 2 |
| Imaging efficacy outcome: patients with endovascular therapy: mTICI score 2b or better at initial angiogram | Before endovascular therapy | With endovascular therapy: mTICI score 2b or better at initial angiogram after thrombolysis before endovascular therapy Parenchymal hematoma 2 |
| Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography at 3-5 days | 3-5 days | Recanalization rate on CTA/MRA at 3-5 days |
| Clinical efficacy outcome: NIHSS change at 7 days | 7 days (plus or minus 2 days) | NIHSS change at 7 days (plus or minus 2 days) |
| Clinical efficacy outcome: vascular death within 90 days | 90 days (plus or minus 7 days) | Vascular death within 90 days (plus or minus 7 days) (stroke, cardiac infarct, pulmonary embolism) |
| Clinical efficacy outcome: major neurological improvement at 24-36 hours ( NIHSS reduction ≥8 or return to 0-1)major neurological improvement at 24-36 hours ( NIHSS reduction ≥8 or return to 0-1) | 24-36 hours | Major neurological improvement at 24-36 hours ( NIHSS reduction \>8 or return to 0-1) |
| Clinical safety outcome: Rate of systemic bleeding | 90 days (plus or minus 7 days) | Rate of systemic bleeding within 90 days (plus or minus 7 days) |
| Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion | 3-5 days | Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion |
| Clinical efficacy outcome: NIHSS change | 24 hours (plus or minus 2 hours) | NIHSS change at 24 hours (plus or minus 2 hours) |
Countries
China
Outcome results
None listed