Clinical trial NCT04516993: CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase II
Official title: Prospective, Multicenter, Open, End-point Blinded, Stratified Block Randomized, Parallel Positive Controlled Clinical Trial of Tenecteplase in Acute Ischemic Stroke With Large Vessel Occlusion Over Time Window
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
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
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: Puer People's Hospital
name: Shanghai 6th People's Hospital
name: Hexigten Traditional Chinese and Mongolian Medicine Hospital
name: Yangpu Hospital, School of Medicine, Tongji University
name: The First Affiliated Hospital of Shanxi Medical University
name: Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine
name: Linyi People's Hospital
name: Shanghai 10th People's Hospital
name: Nanshi Hospital of Nanyang
name: Fudan University
name: Xuzhou Medical University Affiliated Hospital of Huaian
name: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
name: The First Affiliated Hospital of Soochow Medical University
name: Affiliated Haian People's Hospital of Nantong University
name: First Affiliated Hospital of Harbin Medical University
name: the Third Hospital of Mianyang
name: Zhejiang Province People's Hospital
name: Shanghai East Hospital
name: The Central Hospital of Jiaozuo Coal Group
name: Huizhou Municipal Central Hospital
name: Zhejiang University
name: The Second Affiliated Hospital of Chongqing Medical University
name: Ningbo No. 1 Hospital
First posted: 2020-08-18
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours
timeFrame: 4-6 hours
measure: patients with endovascular therapy: mTICI score 2b or better at initial angiogram
timeFrame: Before endovascular therapy
measure: no symptomatic intracranial hemorrhage at 24-36 hours
timeFrame: 24-36 hours
Secondary outcomes:
measure: Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography
timeFrame: 4-6 hours
measure: Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion
timeFrame: 3-5 days
measure: Clinical efficacy outcome: NIHSS change
timeFrame: 24 hours (plus or minus 2 hours)
measure: Clinical efficacy outcome: percent of excellent functional outcome (modified Rankin scale 0-1) at 90 days (plus or minus 7 days)
timeFrame: 90 days (plus or minus 7 days)
measure: Clinical efficacy outcome: percent of good functional outcome (modified Rankin scale 0-2) at 90 days (plus or minus 7 days)
timeFrame: 90 days (plus or minus 7 days)
measure: Clinical efficacy outcome: incident event
timeFrame: 90 days (plus or minus 7 days)
measure: Imaging safety outcome: Intracranial hemorrhage of any volume at 24-36 hours
timeFrame: 24-36 hours
measure: Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours
timeFrame: 24-36 hours
measure: Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours
timeFrame: 24-36 hours
measure: Clinical safety outcome: death within 90 days
timeFrame: 90 days (plus or minus 7 days)
measure: Clinical safety outcome: Rate of systemic bleeding
timeFrame: 90 days (plus or minus 7 days)
measure: Barthel index
timeFrame: 90 days (plus or minus 7 days)
measure: Imaging efficacy outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours
timeFrame: 4-6 hours
measure: Imaging efficacy outcome: patients with endovascular therapy: mTICI score 2b or better at initial angiogram
timeFrame: Before endovascular therapy
measure: Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography at 3-5 days
timeFrame: 3-5 days
measure: Clinical efficacy outcome: NIHSS change at 7 days
timeFrame: 7 days (plus or minus 2 days)
measure: Clinical efficacy outcome: vascular death within 90 days
timeFrame: 90 days (plus or minus 7 days)
measure: 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)
timeFrame: 24-36 hours
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
Study officials:
References: