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 select the best dosage of tenecteplase for acute ischemic stroke patients (onset time 4.5-24h) of large vessel occlusion using early combined CT/MR imaging outcomes
Interventions
DRUGLow dose tenecteplase
Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
DRUGHigh dose tenecteplase
Intravenous (IV) tenecteplase 0.32 mg/kg (single bolus; maximum dose 32 mg)
Sponsors
The First Affiliated Hospital of Shanxi Medical University
Ningbo No. 1 Hospital
Zhejiang Province People's Hospital
Shanghai 5th People's Hospital
Shanghai 10th People's Hospital
Shanghai 6th People's Hospital
The Second Affiliated Hospital of Chongqing Medical University
The Second People's Hospital of Huai'an
Pu'er City People's Hospital
ShuGuang Hospital
Shanghai East Hospital
First People's Hospital of Shenyang
Huashan Hospital
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. Patients presenting with anterior circulation acute ischaemic stroke 2. Time from onset to treatment 4.5h-24h 3. Patient's age is ≥18 years 4. Pre-stroke mRS score of \<= 2 5. Clinically significant acute neurologic deficit 6. Vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on computed tomography angiography (CTA)/MRA 7. 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 8. 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 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 observational trial in 30 days 26. Allergic to the test drug and its ingredients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Favourable 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 |
| Favourable 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 |
| Favourable outcome: 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: NIHSS change | 24-36 hours | NIHSS change at 24-36 hours as a continuous variable |
| Clinical efficacy outcome: excellent functional outcome (modified Rankin scale 0-1) vs (modified Rankin scale 2-6) at 90 days | 90 days | Excellent functional outcome (modified Rankin scale 0-1) vs (modified Rankin scale 2-6) at 90 days. The modified Rankin Scale is a simple 7-point assessment that includes reference to both limitations in activity and changes in lifestyle. 0=No symptoms at all; no limitations and no symptoms. 1=No significant disability despite symptoms; able to carry out all usual duties and activities. 2=Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance. 3=Moderate disability; requiring some help, but able to walk without assistance. 4=Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance. 5=Severe disability: bedridden, incontinent, and requiring constant nursing care and attention. 6=Death. |
| Clinical efficacy outcome: good functional outcome (modified Rankin scale 0-2) vs (modified Rankin scale 3-6) at 90 days | 90 days | Good functional outcome (modified Rankin scale 0-2) vs (modified Rankin scale 3-6) at 90 days. The modified Rankin Scale is a simple 7-point assessment that includes reference to both limitations in activity and changes in lifestyle. 0=No symptoms at all; no limitations and no symptoms. 1=No significant disability despite symptoms; able to carry out all usual duties and activities. 2=Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance. 3=Moderate disability; requiring some help, but able to walk without assistance. 4=Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance. 5=Severe disability: bedridden, incontinent, and requiring constant nursing care and attention. 6=Death. |
| Clinical efficacy outcome: modified Rankin scale shift | 90 days | Modified Rankin scale shift at 90 days. The modified Rankin Scale is a simple 7-point assessment that includes reference to both limitations in activity and changes in lifestyle. 0=No symptoms at all; no limitations and no symptoms. 1=No significant disability despite symptoms; able to carry out all usual duties and activities. 2=Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance. 3=Moderate disability; requiring some help, but able to walk without assistance. 4=Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance. 5=Severe disability: bedridden, incontinent, and requiring constant nursing care and attention. 6=Death. |
| 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 efficacy outcome: recanalization rate on CT/magnetic resonance angiography | 4-6 hours | Recanalization rate on CTA/MRA at 4-6 hours |
| Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours | 24-36 hours | Symptomatic intracranial hemorrhage at 24-36 hours |
| Clinical safety outcome: Poor functional outcome (mRS 5, 6) at 90 days | 90 days | Poor functional outcome (mRS 5, 6) at 90 days. The modified Rankin Scale is a simple 7-point assessment that includes reference to both limitations in activity and changes in lifestyle. 0=No symptoms at all; no limitations and no symptoms. 1=No significant disability despite symptoms; able to carry out all usual duties and activities. 2=Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance. 3=Moderate disability; requiring some help, but able to walk without assistance. 4=Moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance. 5=Severe disability: bedridden, incontinent, and requiring constant nursing care and attention. 6=Death. |
| Clinical safety outcome: Rate of systemic bleeding | 24 hours | Rate of systemic bleeding within 24 hours |
| Barthel index | 90 days | Barthel index at 90 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 safety outcome: parenchymal hematoma 2 at 24-36 hours | 24-36 hours | Parenchymal hematoma 2 at 24-36 hours |
| Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI | 3-5 days | Infarct volume growth (ml) at 3-5 days on MRI |
| Clinical efficacy outcome: 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) |
Countries
China
Outcome results
None listed