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

• ClinicalTrials.gov Identifier: NCT04516993
• Recruitment Status: Recruiting
• First Posted: August 18, 2020
• Last Update Posted: October 25, 2021
• Sponsor: Huashan Hospital
• Collaborators: Shanghai 5th People's Hospital; Shanghai 10th People's Hospital; Shanghai East Hospital; ShuGuang Hospital
• Information provided by (Responsible Party): Qiang Dong, Huashan Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Stroke	Drug: Tenecteplase; Drug: nonthrombolysis drug	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 28, 2021
• Estimated Primary Completion Date: December 1, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tenecteplase arm	Drug: Tenecteplase; Intravenous (IV) tenecteplase 0.25 mg/kg (single bolus; maximum dose 25 mg)
nonthrombolysis drug arm (e.g. Aspirin)	Drug: nonthrombolysis drug; nonthrombolysis drug

Outcome Measures

Primary Outcome Measures :

1. modified Rankin scale change [ Time Frame: 90 days (plus or minus 7 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.

Secondary Outcome Measures :

1. Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography [ Time Frame: 4-6 hours ]
   Recanalization rate on CTA/MRA at 4-6 hours
2. Imaging efficacy outcome: Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion [ Time Frame: 3-5 days ]
   Infarct volume growth (ml) at 3-5 days on MRI or CT perfusion
3. Clinical efficacy outcome: NIHSS change [ Time Frame: 24 hours (plus or minus 2 hours) ]
   NIHSS change at 24 hours (plus or minus 2 hours)
4. Clinical efficacy outcome: percent of excellent functional outcome (modified Rankin scale 0-1) at 90 days (plus or minus 7 days) [ Time Frame: 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)
5. Clinical efficacy outcome: percent of good functional outcome (modified Rankin scale 0-2) at 90 days (plus or minus 7 days) [ Time Frame: 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)
6. Clinical efficacy outcome: incident event [ Time Frame: 90 days (plus or minus 7 days) ]
   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))
7. 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
8. Imaging safety outcome: parenchymal hematoma 2 at 24-36 hours [ Time Frame: 24-36 hours ]
   Parenchymal hematoma 2 at 24-36 hours
9. Imaging safety outcome: Symptomatic intracranial hemorrhage at 24-36 hours [ Time Frame: 24-36 hours ]
   Symptomatic intracranial hemorrhage at 24-36 hours
10. Clinical safety outcome: death within 90 days [ Time Frame: 90 days (plus or minus 7 days) ]
    Death within 90 days (plus or minus 7 days)
11. Clinical safety outcome: Rate of systemic bleeding [ Time Frame: 90 days (plus or minus 7 days) ]
    Rate of systemic bleeding within 90 days (plus or minus 7 days)
12. Barthel index [ Time Frame: 90 days (plus or minus 7 days) ]
    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.
13. Imaging efficacy outcome: patients without endovascular therapy obtained >50% reperfusion at 4-6 hours [ Time Frame: 4-6 hours ]
    Without endovascular therapy: >50% reperfusion on computed tomography perfusion (CTP) at 4-6 hours without Parenchymal hematoma 2
14. Imaging efficacy 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 Parenchymal hematoma 2
15. Imaging efficacy outcome: recanalization rate on CT/magnetic resonance angiography at 3-5 days [ Time Frame: 3-5 days ]
    Recanalization rate on CTA/MRA at 3-5 days
16. Clinical efficacy outcome: NIHSS change at 7 days [ Time Frame: 7 days (plus or minus 2 days) ]
    NIHSS change at 7 days (plus or minus 2 days)
17. Clinical efficacy outcome: vascular death within 90 days [ Time Frame: 90 days (plus or minus 7 days) ]
    Vascular death within 90 days (plus or minus 7 days) (stroke, cardiac infarct, pulmonary embolism)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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. 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

Contacts and Locations

Contacts

Contact: Qiang Dong, MD, PhD; 86-21-52887142; qiang_dong163@163.com

Locations

China, Shanghai

Huashan Hospital; Recruiting

Shanghai, Shanghai, China, 200040

Contact: Qiang Dong +86-21-52887142 qiang_dong163@163.com

Sponsors and Collaborators

Huashan Hospital

Shanghai 5th People's Hospital

Shanghai 10th People's Hospital

Shanghai East Hospital

ShuGuang Hospital

More Information

• Responsible Party: Qiang Dong, Director of Neurology Department, Huashan Hospital
• ClinicalTrials.gov Identifier: NCT04516993
• Other Study ID Numbers: SHDC2020CR1041B
• First Posted: August 18, 2020
• Last Update Posted: October 25, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Qiang Dong, Huashan Hospital:

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

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Tenecteplase; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action