CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase II (CHABLIS-T II)

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

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

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Tenecteplase; Drug: The best treatment selected by local doctors(Aspirin, Recombinant Tissue Plasminogen Activator, Urokinase, Thrombectomy)

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenecteplase arm	Drug: Tenecteplase; Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
Other: Best treatment arm (e.g. Aspirin, Recombinant Tissue Plasminogen Activator, Urokinase, Thrombectomy); The best treatment selected by local doctors	Drug: The best treatment selected by local doctors(Aspirin, Recombinant Tissue Plasminogen Activator, Urokinase, Thrombectomy); Best treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
no symptomatic intracranial hemorrhage at 24-36 hours	No symptomatic intracranial hemorrhage at 24-36 hours	24-36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography	Recanalization rate on CTA/MRA at 4-6 hours	4-6 hours
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
Clinical efficacy outcome: NIHSS change	NIHSS change at 24 hours (plus or minus 2 hours)	24 hours (plus or minus 2 hours)
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)
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)
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)
Imaging safety outcome: Intracranial hemorrhage of any volume at 24-36 hours	Intracranial hemorrhage of any volume at 24-36 hours	24-36 hours
Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours	Parenchymal hematoma 2 at 24-36 hours	24-36 hours
Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours	Symptomatic intracranial hemorrhage at 24-36 hours	24-36 hours
Clinical safety outcome: death within 90 days	Death within 90 days (plus or minus 7 days)	90 days (plus or minus 7 days)
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)
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)
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
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
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
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)
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)
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

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai 10th People's Hospital; Shanghai East Hospital; Zhejiang University; The Second Affiliated Hospital of Chongqing Medical University; The First Affiliated Hospital of Shanxi Medical University; Ningbo No. 1 Hospital; Huizhou Municipal Central Hospital; First Affiliated Hospital of Harbin Medical University; Shanghai 6th People's Hospital; Linyi People's Hospital; Zhejiang Province People's Hospital; Nanshi Hospital of Nanyang; Shanghai Fifth People's Hospital,Fudan University; the Third Hospital of Mianyang; Puer People's Hospital; Hexigten Traditional Chinese and Mongolian Medicine Hospital; Yangpu Hospital, School of Medicine, Tongji University; Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine; 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; The Central Hospital of Jiaozuo Coal Group

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: thrombolysis; magnetic resonance imaging; acute ischemic stroke; tenecteplase; computed tomography; dosage; large vessel occlusion; modified Rankin scale; diffusion weighted imaging; early combined imaging outcomes; time window beyond 4.5 hours
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin; Tissue Plasminogen Activator; Plasminogen; Tenecteplase
• Other Study ID Numbers: SHDC2020CR1041B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No