Clinical trial NCT04086147: CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase
Official title: Chinese Acute Tissue-based Imaging Selection for Lysis in Stroke: a Prospective, Multicentre, Randomized, Open-label, Rater-blinded, Randomized Trial
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: The First Affiliated Hospital of Shanxi Medical University
name: Ningbo No. 1 Hospital
name: Zhejiang Province People's Hospital
name: Shanghai 5th People's Hospital
name: Shanghai 10th People's Hospital
name: Shanghai 6th People's Hospital
name: The Second Affiliated Hospital of Chongqing Medical University
name: The Second People's Hospital of Huai'an
name: Pu'er City People's Hospital
name: ShuGuang Hospital
name: Shanghai East Hospital
name: First People's Hospital of Shenyang
First posted: 2019-09-11
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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
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

Primary outcomes:
measure: Favourable outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours
timeFrame: 4-6 hours
measure: Favourable outcome: patients with endovascular therapy: mTICI score 2b or better at initial angiogram
timeFrame: Before endovascular therapy
measure: Favourable outcome: 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
timeFrame: 3-5 days
measure: Clinical efficacy outcome: major neurological improvement at 24-36 hours ( NIHSS reduction ≥8 or return to 0-1)
timeFrame: 24-36 hours
measure: Clinical efficacy outcome: NIHSS change
timeFrame: 24-36 hours
measure: Clinical efficacy outcome: excellent functional outcome (modified Rankin scale 0-1) vs (modified Rankin scale 2-6) at 90 days
timeFrame: 90 days
measure: Clinical efficacy outcome: good functional outcome (modified Rankin scale 0-2) vs (modified Rankin scale 3-6) at 90 days
timeFrame: 90 days
measure: Clinical efficacy outcome: modified Rankin scale shift
timeFrame: 90 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: Poor functional outcome (mRS 5, 6) at 90 days
timeFrame: 90 days
measure: Clinical safety outcome: Rate of systemic bleeding
timeFrame: 24 hours
measure: Barthel index
timeFrame: 90 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
Study officials:
References: