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

Chinese Acute Tissue-based Imaging Selection for Lysis in Stroke: a Prospective, Multicentre, Randomized, Open-label, Rater-blinded, Randomized Trial

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

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Low dose tenecteplase; Drug: High dose tenecteplase

• Study Type: Interventional
• Enrollment (Actual): 86
• 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 and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low dose tenecteplase	Drug: Low dose tenecteplase; Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
EXPERIMENTAL: High dose tenecteplase	Drug: High dose tenecteplase; Intravenous (IV) tenecteplase 0.32 mg/kg (single bolus; maximum dose 32 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Favourable 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	4-6 hours
Favourable 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	Before endovascular therapy
Favourable outcome: 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 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
Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI	Infarct volume growth (ml) at 3-5 days on MRI	3-5 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)	24-36 hours
Clinical efficacy outcome: NIHSS change	NIHSS change at 24-36 hours as a continuous variable	24-36 hours
Clinical efficacy outcome: excellent functional outcome (modified Rankin scale 0-1) vs (modified Rankin scale 2-6) at 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.	90 days
Clinical efficacy outcome: good functional outcome (modified Rankin scale 0-2) vs (modified Rankin scale 3-6) at 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.	90 days
Clinical efficacy outcome: modified Rankin scale shift	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.	90 days
Clinical safety outcome: Poor functional outcome (mRS 5, 6) at 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.	90 days
Clinical safety outcome: Rate of systemic bleeding	Rate of systemic bleeding within 24 hours	24 hours
Barthel index	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.	90 days

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai 10th People's Hospital; Shanghai East Hospital; The Second Affiliated Hospital of Chongqing Medical University; The Second People's Hospital of Huai'an; The First Affiliated Hospital of Shanxi Medical University; Ningbo No. 1 Hospital; ShuGuang Hospital; Shanghai 6th People's Hospital; Shanghai 5th People's Hospital; Pu'er City People's Hospital; Zhejiang Province People's Hospital; First People's Hospital of Shenyang

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 9, 2019
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): December 31, 2021

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (ACTUAL): September 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

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; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: 2017YFC1308201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No