CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase II

Stroke Clinical Trial

— CHABLIS-T 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04516993
• Other study ID #: SHDC2020CR1041B
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2021
• Est. completion date: September 30, 2023

Study information

• Verified date: November 2023
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Tenecteplase
Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
• The best treatment selected by local doctors(Aspirin, Recombinant Tissue Plasminogen Activator, Urokinase, Thrombectomy)
Best treatment arm

Locations

Country	Name	City	State
China	Huashan Hospital	Shanghai	Shanghai

Sponsors (24)

Lead Sponsor

Collaborator

Huashan Hospital

Affiliated Haian People's Hospital of Nantong University, First Affiliated Hospital of Harbin Medical University, Hexigten Traditional Chinese and Mongolian Medicine Hospital, Huizhou Municipal Central Hospital, Linyi People's Hospital, Nanshi Hospital of Nanyang, Ningbo No. 1 Hospital, Puer People's Hospital, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 10th People's Hospital, Shanghai 6th People's Hospital, Shanghai East Hospital, Shanghai Fifth People's Hospital,Fudan University, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, The Central Hospital of Jiaozuo Coal Group, The First Affiliated Hospital of Shanxi Medical University, The First Affiliated Hospital of Soochow Medical University, The Second Affiliated Hospital of Chongqing Medical University, the Third Hospital of Mianyang, Xuzhou Medical University Affiliated Hospital of Huaian, Yangpu Hospital, School of Medicine, Tongji University, Zhejiang Province People's Hospital, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	patients without endovascular therapy obtained >50% reperfusion at 4-6 hours	Without endovascular therapy: >50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours	4-6 hours
Primary	patients with endovascular therapy: mTICI score 2b or better at initial angiogram	With endovascular therapy: mTICI score 2b or better at initial angiogram after thrombolysis before endovascular therapy	Before endovascular therapy
Primary	no symptomatic intracranial hemorrhage at 24-36 hours	No symptomatic intracranial hemorrhage at 24-36 hours	24-36 hours
Secondary	Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography	Recanalization rate on CTA/MRA at 4-6 hours	4-6 hours
Secondary	Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion	Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion	3-5 days
Secondary	Clinical efficacy outcome: NIHSS change	NIHSS change at 24 hours (plus or minus 2 hours)	24 hours (plus or minus 2 hours)
Secondary	Clinical efficacy outcome: percent of excellent functional outcome (modified Rankin scale 0-1) at 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)	90 days (plus or minus 7 days)
Secondary	Clinical efficacy outcome: percent of good functional outcome (modified Rankin scale 0-2) at 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)	90 days (plus or minus 7 days)
Secondary	Clinical efficacy outcome: incident event	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))	90 days (plus or minus 7 days)
Secondary	Imaging safety outcome: Intracranial hemorrhage of any volume at 24-36 hours	Intracranial hemorrhage of any volume at 24-36 hours	24-36 hours
Secondary	Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours	Parenchymal hematoma 2 at 24-36 hours	24-36 hours
Secondary	Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours	Symptomatic intracranial hemorrhage at 24-36 hours	24-36 hours
Secondary	Clinical safety outcome: death within 90 days	Death within 90 days (plus or minus 7 days)	90 days (plus or minus 7 days)
Secondary	Clinical safety outcome: Rate of systemic bleeding	Rate of systemic bleeding within 90 days (plus or minus 7 days)	90 days (plus or minus 7 days)
Secondary	Barthel index	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.	90 days (plus or minus 7 days)
Secondary	Imaging efficacy outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours	Without endovascular therapy: >50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours without Parenchymal hematoma 2	4-6 hours
Secondary	Imaging efficacy outcome: patients with endovascular therapy: mTICI score 2b or better at initial angiogram	With endovascular therapy: mTICI score 2b or better at initial angiogram after thrombolysis before endovascular therapy Parenchymal hematoma 2	Before endovascular therapy
Secondary	Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography at 3-5 days	Recanalization rate on CTA/MRA at 3-5 days	3-5 days
Secondary	Clinical efficacy outcome: NIHSS change at 7 days	NIHSS change at 7 days (plus or minus 2 days)	7 days (plus or minus 2 days)
Secondary	Clinical efficacy outcome: vascular death within 90 days	Vascular death within 90 days (plus or minus 7 days) (stroke, cardiac infarct, pulmonary embolism)	90 days (plus or minus 7 days)
Secondary	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)	Major neurological improvement at 24-36 hours ( NIHSS reduction >8 or return to 0-1)	24-36 hours