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

Stroke Clinical Trial

— CHABLIS-T  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04086147
• Other study ID #: 2017YFC1308201
• Status: Completed
• Phase: Phase 2
• Start date: December 9, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2022
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

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

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Low dose tenecteplase
Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
• High dose tenecteplase
Intravenous (IV) tenecteplase 0.32 mg/kg (single bolus; maximum dose 32 mg)

Locations

Country	Name	City	State
China	Huashan Hospital	Shanghai	Shanghai

Sponsors (13)

Lead Sponsor

Collaborator

Huashan Hospital

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Favourable outcome: 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	Infarct volume growth (ml) at 3-5 days on MRI	3-5 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)	24-36 hours
Secondary	Clinical efficacy outcome: NIHSS change	NIHSS change at 24-36 hours as a continuous variable	24-36 hours
Secondary	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
Secondary	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
Secondary	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
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: 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
Secondary	Clinical safety outcome: Rate of systemic bleeding	Rate of systemic bleeding within 24 hours	24 hours
Secondary	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