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

Overview

To select the best dosage of tenecteplase for acute ischemic stroke patients (onset time >4.5h) of large vessel occlusion using early combined imaging outcomes

Full Title of Study: “Chinese Acute Tissue-based Imaging Selection for Lysis in Stroke: a Prospective, Multicentre, Randomized, Open-label, Blinded Endpoint, Randomized Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: December 2020

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Low dose tenecteplase
  • Experimental: High dose tenecteplase

Clinical Trial Outcome Measures

Primary Measures

  • Favourable outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours and no bleeding at 24 hours
    • Time Frame: 4-6 hours, 24 hours
    • Without endovascular therapy: >50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours, no bleeding at 24 hours
  • Favourable outcome: patients with endovascular therapy: mTICI score 2b or better at initial angiogram
    • Time Frame: Before endovascular therapy
    • With endovascular therapy: mTICI score 2b or better at initial angiogram after thrombolysis before endovascular therapy

Secondary Measures

  • Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI
    • Time Frame: 3-5 days
    • Infarct volume growth (ml) at 3-5 days on MRI
  • Imaging efficacy outcome: recanalization on magnetic resonance angiography (MRA) at 3-5 days
    • Time Frame: 3-5 days
    • Recanalization or not on MRA at 3-5 days
  • Clinical efficacy outcome: major neurological improvement at 24 hours ( NIHSS reduction ≥8 or return to 0-1)
    • Time Frame: 24 hours
    • Major neurological improvement at 24 hours ( NIHSS reduction ≥8 or return to 0-1)
  • Clinical efficacy outcome: NIHSS change
    • Time Frame: 24 hours
    • NIHSS change at 24 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 90 days
    • 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
    • Time Frame: 24-36 hours
    • Intracranial hemorrhage of any volume at 24-36 hours
  • Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours
    • Time Frame: 24-36 hours
    • Parenchymal hematoma 2 at 24-36 hours
  • Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours
    • Time Frame: 24-36 hours
    • Symptomatic intracranial hemorrhage at 24-36 hours
  • Clinical safety outcome: Poor functional outcome (mRS 5, 6) at 90 days
    • Time Frame: 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
    • Time Frame: 24 hours
    • Rate of systemic bleeding within 24 hours
  • Barthel index
    • Time Frame: 90 days
    • 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.

Participating in This Clinical Trial

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 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 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. Contra indication to imaging with CT/magnetic resonance imaging with contrast agents

5. Infarct core >1/3 middle cerebral artery (MCA) territory

6. Platelet count < 100×10^9/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 heparin within 48 hours, or 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. Symptoms suggest subarachnoid hemorrhage. Risks were considered by the investigator

18. Hereditary or acquired haemorrhagic diathesis

19. Active internal bleeding

20. Symptoms suggestive or recent acute pancreatitis

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 trial in 30 days

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Huashan Hospital
  • Collaborator
    • The First Affiliated Hospital of Zhengzhou University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Qiang Dong, Director of Neurology Department – Huashan Hospital
  • Overall Contact(s)
    • Qiang Dong, MD, PhD, 86-21-52887142, qiang_dong163@163.com

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