Back to resultsCHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase (CHABLIS-T)
Primary Purpose
Stroke
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Low dose tenecteplase
High dose tenecteplase
Sponsored by
About this trial
This is an interventional treatment trial for Stroke focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- Patients presenting with anterior circulation acute ischaemic stroke
- Time from onset to treatment 4.5h-24h
- Patient's age is ≥18 years
- Pre-stroke mRS score of <= 2
- Clinically significant acute neurologic deficit
- Vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on computed tomography angiography (CTA)/MRA
- 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
- Informed consent was obtained from patients.
Exclusion Criteria:
- Intracranial hemorrhage or subarachnoid hemorrhage identified by CT or MRI
- Rapidly improving symptoms (patient with an NIHSS score decrease to < 4 at randomization)
- Pre-stroke mRS score of > 2
- Contraindication to imaging with CT/magnetic resonance imaging with contrast agents
- Infarct core >1/3 middle cerebral artery (MCA) territory
- Platelet count < 100x10^9/L
- Symptoms were caused by low blood glucose < 2.7 mmol/l
- Severe uncontrolled hypertension, i.e. systolic blood pressure >= 180 mmHg or diastolic blood pressure >=100 mmHg
- Current use of warfarin with a prolonged prothrombin time (INR > 1.7 or prothrombin time > 15s)
- Use of low molecular weight heparin within 24 hours
- Use of non-vitamin K antagonist oral anticoagulants (NOACs) within 48 hours
- Use of glycoprotein IIb - IIIa inhibitors within 72 hours.
- Arterial puncture at noncompressible site in previous 7 days
- Major surgery in previous 14 days which poses risk in the opinion of the investigator
- Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days)
- Significant head trauma or prior stroke in previous 3 months
- History of previous intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Risks were considered by the investigator
- Hereditary or acquired haemorrhagic diathesis
- Active internal bleeding
- Symptoms suggestive or recent acute pancreatitis, active gastrointestinal ulcer
- Severe liver disease, including liver failure, cirrhosis, portal hypertension and active hepatitis
- Pregnancy
- Various dying diseases with life expectancy ≤3 months
- Other conditions in which doctors believe that participating in this study may be harmful to the patient
- Patients participated in any observational trial in 30 days
- Allergic to the test drug and its ingredients
Sites / Locations
- Huashan Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low dose tenecteplase
High dose tenecteplase
Arm Description
Outcomes
Primary Outcome Measures
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
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
Favourable outcome: no symptomatic intracranial hemorrhage at 24-36 hours
No symptomatic intracranial hemorrhage at 24-36 hours
Secondary Outcome Measures
Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography
Recanalization rate on CTA/MRA at 4-6 hours
Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI
Infarct volume growth (ml) at 3-5 days on MRI
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)
Clinical efficacy outcome: NIHSS change
NIHSS change at 24-36 hours as a continuous variable
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.
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.
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.
Imaging safety outcome: Intracranial hemorrhage of any volume at 24-36 hours
Intracranial hemorrhage of any volume at 24-36 hours
Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours
Parenchymal hematoma 2 at 24-36 hours
Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours
Symptomatic intracranial hemorrhage at 24-36 hours
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.
Clinical safety outcome: Rate of systemic bleeding
Rate of systemic bleeding within 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.
Full Information
NCT ID
NCT04086147
First Posted
April 15, 2019
Last Updated
March 30, 2022
Sponsor
Huashan Hospital
Collaborators
The First Affiliated Hospital of Shanxi Medical University, Ningbo No. 1 Hospital, Zhejiang Province People's Hospital, Shanghai 5th People's Hospital, Shanghai 10th People's Hospital, Shanghai 6th People's Hospital, The Second Affiliated Hospital of Chongqing Medical University, The Second People's Hospital of Huai'an, Pu'er City People's Hospital, ShuGuang Hospital, Shanghai East Hospital, First People's Hospital of Shenyang
1. Study Identification
Unique Protocol Identification Number
NCT04086147
Brief Title
CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase
Acronym
CHABLIS-T
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
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
December 9, 2019 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huashan Hospital
Collaborators
The First Affiliated Hospital of Shanxi Medical University, Ningbo No. 1 Hospital, Zhejiang Province People's Hospital, Shanghai 5th People's Hospital, Shanghai 10th People's Hospital, Shanghai 6th People's Hospital, The Second Affiliated Hospital of Chongqing Medical University, The Second People's Hospital of Huai'an, Pu'er City People's Hospital, ShuGuang Hospital, Shanghai East Hospital, First People's Hospital of Shenyang
4. Oversight
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
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low dose tenecteplase
Arm Type
Experimental
Arm Title
High dose tenecteplase
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Low dose tenecteplase
Intervention Description
Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
Intervention Type
Drug
Intervention Name(s)
High dose tenecteplase
Intervention Description
Intravenous (IV) tenecteplase 0.32 mg/kg (single bolus; maximum dose 32 mg)
Primary Outcome Measure Information:
Title
Favourable outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours
Description
Without endovascular therapy: >50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours
Time Frame
4-6 hours
Title
Favourable outcome: patients with endovascular therapy: mTICI score 2b or better at initial angiogram
Description
With endovascular therapy: mTICI score 2b or better at initial angiogram after thrombolysis before endovascular therapy
Time Frame
Before endovascular therapy
Title
Favourable outcome: no symptomatic intracranial hemorrhage at 24-36 hours
Description
No symptomatic intracranial hemorrhage at 24-36 hours
Time Frame
24-36 hours
Secondary Outcome Measure Information:
Title
Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography
Description
Recanalization rate on CTA/MRA at 4-6 hours
Time Frame
4-6 hours
Title
Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI
Description
Infarct volume growth (ml) at 3-5 days on MRI
Time Frame
3-5 days
Title
Clinical efficacy outcome: major neurological improvement at 24-36 hours ( NIHSS reduction ≥8 or return to 0-1)
Description
Major neurological improvement at 24-36 hours ( NIHSS reduction >8 or return to 0-1)
Time Frame
24-36 hours
Title
Clinical efficacy outcome: NIHSS change
Description
NIHSS change at 24-36 hours as a continuous variable
Time Frame
24-36 hours
Title
Clinical efficacy outcome: excellent functional outcome (modified Rankin scale 0-1) vs (modified Rankin scale 2-6) at 90 days
Description
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.
Time Frame
90 days
Title
Clinical efficacy outcome: good functional outcome (modified Rankin scale 0-2) vs (modified Rankin scale 3-6) at 90 days
Description
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.
Time Frame
90 days
Title
Clinical efficacy outcome: modified Rankin scale shift
Description
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.
Time Frame
90 days
Title
Imaging safety outcome: Intracranial hemorrhage of any volume at 24-36 hours
Description
Intracranial hemorrhage of any volume at 24-36 hours
Time Frame
24-36 hours
Title
Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours
Description
Parenchymal hematoma 2 at 24-36 hours
Time Frame
24-36 hours
Title
Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours
Description
Symptomatic intracranial hemorrhage at 24-36 hours
Time Frame
24-36 hours
Title
Clinical safety outcome: Poor functional outcome (mRS 5, 6) at 90 days
Description
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.
Time Frame
90 days
Title
Clinical safety outcome: Rate of systemic bleeding
Description
Rate of systemic bleeding within 24 hours
Time Frame
24 hours
Title
Barthel index
Description
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.
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients presenting with anterior circulation acute ischaemic stroke
Time from onset to treatment 4.5h-24h
Patient's age is ≥18 years
Pre-stroke mRS score of <= 2
Clinically significant acute neurologic deficit
Vessel occlusion or severe stenosis ( ICA, MCA-M1/M2, ACA) on computed tomography angiography (CTA)/MRA
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
Informed consent was obtained from patients.
Exclusion Criteria:
Intracranial hemorrhage or subarachnoid hemorrhage identified by CT or MRI
Rapidly improving symptoms (patient with an NIHSS score decrease to < 4 at randomization)
Pre-stroke mRS score of > 2
Contraindication to imaging with CT/magnetic resonance imaging with contrast agents
Infarct core >1/3 middle cerebral artery (MCA) territory
Platelet count < 100x10^9/L
Symptoms were caused by low blood glucose < 2.7 mmol/l
Severe uncontrolled hypertension, i.e. systolic blood pressure >= 180 mmHg or diastolic blood pressure >=100 mmHg
Current use of warfarin with a prolonged prothrombin time (INR > 1.7 or prothrombin time > 15s)
Use of low molecular weight heparin within 24 hours
Use of non-vitamin K antagonist oral anticoagulants (NOACs) within 48 hours
Use of glycoprotein IIb - IIIa inhibitors within 72 hours.
Arterial puncture at noncompressible site in previous 7 days
Major surgery in previous 14 days which poses risk in the opinion of the investigator
Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days)
Significant head trauma or prior stroke in previous 3 months
History of previous intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm. Risks were considered by the investigator
Hereditary or acquired haemorrhagic diathesis
Active internal bleeding
Symptoms suggestive or recent acute pancreatitis, active gastrointestinal ulcer
Severe liver disease, including liver failure, cirrhosis, portal hypertension and active hepatitis
Pregnancy
Various dying diseases with life expectancy ≤3 months
Other conditions in which doctors believe that participating in this study may be harmful to the patient
Patients participated in any observational trial in 30 days
Allergic to the test drug and its ingredients
Facility Information:
Facility Name
Huashan Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
12. IPD Sharing Statement
Learn more about this trial
CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke -Tenecteplase
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