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Intravenous Tenecteplase Plus EVT Versus EVT Alone on 4.5 to 24 Hours After Basilar Artery Occlusion

Primary Purpose

Basilar Artery Occlusion, Acute Cerebrovascular Accident, Stroke Due to Basilar Artery Occlusion

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Tenecteplase
Endovascular thrombectomy
Sponsored by
The First Affiliated Hospital of University of Science and Technology of China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Basilar Artery Occlusion focused on measuring Thrombectomy, Tenecteplase, Mechanical Thrombectomy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients presenting with posterior circulation ischemic stroke symptoms due to basilar artery occlusion or vertebral artery occlusions that prevent antegrade flow into the basilar artery; Time from stroke onset to randomization within 4.5-24 hours of estimated time of basilar artery occlusion; Patient's age≥18 years; Presence of basilar artery or vertebral artery occlusion, confirmed by CT Angiography (CTA), MR Angiography (MRA) or Digital Subtraction Angiography (DSA). In cases of vertebral artery occlusion, the occlusion must completely prevent antegrade flow into the basilar artery; Patients presenting with acute ischemic stroke eligible using standard criteria (except for time window) to receive both endovascular thrombectomy and intravenous thrombolysis; Baseline National Institutes of Health Stroke Scale (NIHSS) score≥ 10 at the time of neuroimaging; The patient or patient's legal representative signs the informed consent form. Exclusion Criteria: CT or MR evidence of intracerebral hemorrhage (the presence of < 10 microbleeds is allowed); Pre-stroke modified Rankin scale (mRS) score of ≥ 2; Posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) on CT/ CTA-Source Images<6; PC-ASPECTS on magnetic resonance imaging-diffusion weighted imaging (MRI-DWI) <5; Pregnant or lactating women; Allergy to contrast agent or nitinol alloy; Life expectancy<1 year; CTA/MRA/DSA show vascular tortuosity, vascular variation or artery dissection, which would make it difficult to perform endovascular treatment; Participating in other clinical trials; Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, which cannot be controlled by antihypertensive drugs; Genetic or acquired hemorrhagic diathesis, lack of anticoagulant factor; or oral anticoagulant with international normalized ratio (INR) > 1.7, or novel oral anticoagulant within prior 48 hours; Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L), platelet< 100*109/L; Renal insufficiency defined as serum creatinine >2.0 mg/dl (or 176.8 μ mol/l) or a glomerular filtration rate <30 mL/min or the need for hemodialysis or peritoneal dialysis; Patients who cannot complete 90-day follow-up (such as patients without fixed residence, overseas patients, etc); The patient has acute ischemic cerebral infarction within 3 months from randomization; The patient had a history of or clinical suspicion for cerebral vasculitis or infectious endocarditis; The patient has nervous system disease or mental disorder before stroke onset, which may affect the assessment of their condition; CT or MR examination showed large cerebellar infarction with obvious space occupying effect and compression of the fourth ventricle; Patients with extensive bilateral thalamic or extensive bilateral brainstem infarction on CT or MR examination; CTA/MRA/DSA show both anterior and posterior circulation large vessel occlusion; Patients with intracranial tumors (except small meningiomas); Patients who received intravenous thrombolytics treatment before the randomization;

Sites / Locations

  • The First Affiliated Hospital of University of Science and Technology of ChinaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous tenecteplase+endovascular thrombectomy

Endovascular thrombectomy alone

Arm Description

Patients will receive intravenous tenecteplase (0.25mg/kg, max 25mg) plus endovascular thrombectomy.

Patients will receive endovascular thrombectomy alone.

Outcomes

Primary Outcome Measures

Proportion of patients with modified Rankin Score 0-2 at day 90 (±14 days)
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)

Secondary Outcome Measures

Proportion of patients with modified Rankin Score 0-3 at day 90 (±14 days)
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Ordinal Shift analysis of modified Rankin Score at day 90 (±14 days)
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Score on the NIHSS at 24 hours
The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.
Score on the NIHSS at 5-7 days or discharge
The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.
Proportion of patients with modified Rankin Score 0-1 at day 90 (±14 days)
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Proportion of patients with modified Rankin Score 0-4 at day 90 (±14 days)
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Score on the EuroQoL 5-dimensions 5-level (EQ5D-5L) at 90 days (±14 days)
Health-related quality of life, assessed with EQ-5D-5L
level of activities of daily living (Barthel index, BI) at 90 days (±14 days)
Level of activities of daily living
Successful reperfusion (Extended thrombolysis in cerebral infarction [eTICI] score 2b50-3) on digital substraction angiography (DSA) prior to thrombectomy
Evaluate effect of intravenous thrombolysis on reperfusion
Successful reperfusion on final angiography of thrombectomy
Evaluate effect of thrombectomy on reperfusion
Successful recanalization on CT or MR angiography within 72 hours
Evaluate vascular patency after treatment
Infarct volume (Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score, PC-ASPECTS) evaluated on CT or MRI within 72 hours
PC-ASPECTS=10 indicates a normal scan, PC-ASPECTS=0 indicates early ischemic changes or hypoattenuation in all above territories. 1 or 2 points each are subtracted for early ischemic changes or hypoattenuation in: left or right thalamus, cerebellum or posterior cerebral artery territory, respectively (1 point); any part of midbrain or pons (2 points)

Full Information

First Posted
January 18, 2023
Last Updated
July 16, 2023
Sponsor
The First Affiliated Hospital of University of Science and Technology of China
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1. Study Identification

Unique Protocol Identification Number
NCT05701956
Brief Title
Intravenous Tenecteplase Plus EVT Versus EVT Alone on 4.5 to 24 Hours After Basilar Artery Occlusion
Official Title
Intravenous Tenecteplase Plus Endovascular Thrombectomy Versus Endovascular Thrombectomy Alone on 4.5 to 24 Hours After Stroke Due to Basilar Artery Occlusion -a Multicenter, Randomized Controlled, Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 16, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of University of Science and Technology of China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To assess the effect of intravenous tenecteplase plus endovascular thrombectomy (EVT) compared to EVT alone on 4.5 to 24 hours after stroke due to basilar artery occlusion.
Detailed Description
Background and Rationale: Recently, two prospective multicenter RCT (ATTENTION and BAOCHE trials) have shown a significantly beneficial effect of EVT in patients with an acute symptomatic basilar artery occlusion. The EXTEND-IA TNK trial demonstrated that intravenous thrombolysis with tenecteplase is superior to alteplase before EVT for anterior circulation large vessel occlusion strokes. However, it is unclear whether intravenous tenecteplase bridging with EVT is superior to EVT alone in the extended window patients with basilar artery occlusion. Therefore, additional studies are needed to explore the potential benefit of intravenous tenecteplase in these patients. Study design: Multicenter, prospective, controlled clinical trial with open-label treatment and blind outcome assessment (PROBE) of intravenous tenecteplase plus EVT versus EVT alone. The trial has observer blinded assessment of the primary outcome and neuroimaging at baseline and follow up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basilar Artery Occlusion, Acute Cerebrovascular Accident, Stroke Due to Basilar Artery Occlusion
Keywords
Thrombectomy, Tenecteplase, Mechanical Thrombectomy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
332 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous tenecteplase+endovascular thrombectomy
Arm Type
Experimental
Arm Description
Patients will receive intravenous tenecteplase (0.25mg/kg, max 25mg) plus endovascular thrombectomy.
Arm Title
Endovascular thrombectomy alone
Arm Type
Active Comparator
Arm Description
Patients will receive endovascular thrombectomy alone.
Intervention Type
Drug
Intervention Name(s)
Tenecteplase
Other Intervention Name(s)
TNK, TNK-tPA, TNKase, rhTNK-tPA
Intervention Description
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds) before endovascular thrombectomy
Intervention Type
Procedure
Intervention Name(s)
Endovascular thrombectomy
Other Intervention Name(s)
thrombectomy
Intervention Description
The choice of endovascular thrombectomy strategy will be made by the treating neurointerventionist. All thrombectomy devices for endovascular treatment, which are approved by CFDA for this purpose, are allowed in the trial.
Primary Outcome Measure Information:
Title
Proportion of patients with modified Rankin Score 0-2 at day 90 (±14 days)
Description
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Time Frame
90 (± 14 days) after procedure
Secondary Outcome Measure Information:
Title
Proportion of patients with modified Rankin Score 0-3 at day 90 (±14 days)
Description
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Time Frame
90 (± 14 days) after procedure
Title
Ordinal Shift analysis of modified Rankin Score at day 90 (±14 days)
Description
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Time Frame
90 (± 14 days) after procedure
Title
Score on the NIHSS at 24 hours
Description
The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.
Time Frame
24 hours after procedure
Title
Score on the NIHSS at 5-7 days or discharge
Description
The NIHSS is an ordinal hierarchical scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.
Time Frame
5-7 days or discharge after procedure
Title
Proportion of patients with modified Rankin Score 0-1 at day 90 (±14 days)
Description
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Time Frame
90 (± 14 days) after procedure
Title
Proportion of patients with modified Rankin Score 0-4 at day 90 (±14 days)
Description
modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Time Frame
90 (± 14 days) after procedure
Title
Score on the EuroQoL 5-dimensions 5-level (EQ5D-5L) at 90 days (±14 days)
Description
Health-related quality of life, assessed with EQ-5D-5L
Time Frame
90 (± 14 days) after procedure
Title
level of activities of daily living (Barthel index, BI) at 90 days (±14 days)
Description
Level of activities of daily living
Time Frame
90 (± 14 days) after procedure
Title
Successful reperfusion (Extended thrombolysis in cerebral infarction [eTICI] score 2b50-3) on digital substraction angiography (DSA) prior to thrombectomy
Description
Evaluate effect of intravenous thrombolysis on reperfusion
Time Frame
within 5 minutes at angiography
Title
Successful reperfusion on final angiography of thrombectomy
Description
Evaluate effect of thrombectomy on reperfusion
Time Frame
Within 5 minutes at final angiography of thrombectomy
Title
Successful recanalization on CT or MR angiography within 72 hours
Description
Evaluate vascular patency after treatment
Time Frame
Within 72 hours after procedure
Title
Infarct volume (Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score, PC-ASPECTS) evaluated on CT or MRI within 72 hours
Description
PC-ASPECTS=10 indicates a normal scan, PC-ASPECTS=0 indicates early ischemic changes or hypoattenuation in all above territories. 1 or 2 points each are subtracted for early ischemic changes or hypoattenuation in: left or right thalamus, cerebellum or posterior cerebral artery territory, respectively (1 point); any part of midbrain or pons (2 points)
Time Frame
Within 72 hours after procedure
Other Pre-specified Outcome Measures:
Title
Overall mortality at 7 (± 2 days) and 90 (± 14 days)
Description
evaluate death rate
Time Frame
7 (± 2 days) and 90 (± 14 days) after procedure
Title
Symptomatic intracerebral hemorrhage (sICH) within 72 hours
Description
SICH means any hemorrhage with neurological deterioration, as indicated by an NIHSS score that was higher by ≥4 points than the value at baseline or the lowest value in the first 72 hours or any hemorrhage leading to death
Time Frame
Within 72 hours after procedure
Title
Any intracerebral hemorrhage within 72 hours
Description
Evaluate intracerebral hemorrhage
Time Frame
Within 72 hours after procedure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients presenting with posterior circulation ischemic stroke symptoms due to basilar artery occlusion or vertebral artery occlusions that prevent antegrade flow into the basilar artery; Time from stroke onset to randomization within 4.5-24 hours of estimated time of basilar artery occlusion; Patient's age≥18 years; Presence of basilar artery or vertebral artery occlusion, confirmed by CT Angiography (CTA), MR Angiography (MRA) or Digital Subtraction Angiography (DSA). In cases of vertebral artery occlusion, the occlusion must completely prevent antegrade flow into the basilar artery; Patients presenting with acute ischemic stroke eligible using standard criteria (except for time window) to receive both endovascular thrombectomy and intravenous thrombolysis; Baseline National Institutes of Health Stroke Scale (NIHSS) score≥ 10 at the time of neuroimaging; The patient or patient's legal representative signs the informed consent form. Exclusion Criteria: CT or MR evidence of intracerebral hemorrhage (the presence of < 10 microbleeds is allowed); Pre-stroke modified Rankin scale (mRS) score of ≥ 2; Posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) on CT/ CTA-Source Images<6; PC-ASPECTS on magnetic resonance imaging-diffusion weighted imaging (MRI-DWI) <5; Pregnant or lactating women; Allergy to contrast agent or nitinol alloy; Life expectancy<1 year; CTA/MRA/DSA show vascular tortuosity, vascular variation or artery dissection, which would make it difficult to perform endovascular treatment; Participating in other clinical trials; Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, which cannot be controlled by antihypertensive drugs; Genetic or acquired hemorrhagic diathesis, lack of anticoagulant factor; or oral anticoagulant with international normalized ratio (INR) > 1.7, or novel oral anticoagulant within prior 48 hours; Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L), platelet< 100*109/L; Renal insufficiency defined as serum creatinine >2.0 mg/dl (or 176.8 μ mol/l) or a glomerular filtration rate <30 mL/min or the need for hemodialysis or peritoneal dialysis; Patients who cannot complete 90-day follow-up (such as patients without fixed residence, overseas patients, etc); The patient has acute ischemic cerebral infarction within 3 months from randomization; The patient had a history of or clinical suspicion for cerebral vasculitis or infectious endocarditis; The patient has nervous system disease or mental disorder before stroke onset, which may affect the assessment of their condition; CT or MR examination showed large cerebellar infarction with obvious space occupying effect and compression of the fourth ventricle; Patients with extensive bilateral thalamic or extensive bilateral brainstem infarction on CT or MR examination; CTA/MRA/DSA show both anterior and posterior circulation large vessel occlusion; Patients with intracranial tumors (except small meningiomas); Patients who received intravenous thrombolytics treatment before the randomization;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Hu, MD
Phone
+8615155510611
Email
andinghu@ustc.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Hu, MD
Organizational Affiliation
The First Affiliated Hospital of University of Science and Technology of China
Official's Role
Study Chair
Facility Information:
Facility Name
The First Affiliated Hospital of University of Science and Technology of China
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Hu, MD
Phone
+8615155510611
Email
andinghu@ustc.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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Intravenous Tenecteplase Plus EVT Versus EVT Alone on 4.5 to 24 Hours After Basilar Artery Occlusion

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