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Endovascular Thrombectomy With and Without Intravenous Thrombolysis in Extended Time Window

Primary Purpose

Stroke, Acute Ischemic

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Intravenous thrombolysis agents
endovascular thrombectomy
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke, Acute Ischemic

Eligibility Criteria

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

Inclusion Criteria: Patient/Legally Authorized Representative has signed the Informed Consent form Age ≥ 18 Clinical signs consistent with an acute ischemic stroke Neurological deficit with a NIHSS of ≥ 6 (deficits judged to be clearly disabling at presentation) Patient is eligible for intravenous thrombolysis Patient is eligible for endovascular treatment Randomization no later than 8 hours 45 minutes after stroke symptom onset and initiation of IV t-PA must be started within 9 hours of stroke symptoms onset (for stroke with unknown time of onset, the midpoint of the time last known to be well and symptom recognition time) ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA or CTA (including the reconstructed CTA derived from CTP). And target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml, mismatch ratio is >/= 1.8 and mismatch volume is >/= 15 ml) Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6 based on baseline CT or MR imaging (MRI) (a region has to have diffusion abnormality in 20% or more of its volume to be considered MR-ASPECTS positive) Exclusion Criteria: Acute intracranial hemorrhage Any contraindication for IV t-PA Pre-treatment with IV t-PA Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys Known current participation in a clinical trial (investigational drug or medical device) Renal insufficiency as defined by a serum creatinine > 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) < 30 mL/min or requirement for hemodialysis or peritoneal dialysis Severe comorbid condition with life expectancy less than 90 days at baseline Known advanced dementia or significant pre-stroke disability (mRS score of ≥2) Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad) Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day). Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma) Radiological confirmed evidence of cerebral vasculitis CTA or MRA evidence of carotid artery dissection Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA

Sites / Locations

  • The Second Affiliated Hospital of Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous thrombolysis bridging with endovascular thrombectomy

Direct endovascular thrombectomy without intravenous thrombolysis

Arm Description

Outcomes

Primary Outcome Measures

Good clinical outcome
Score in modified Rankin Scale (mRS) ≤ 2 (mRS is short for modified ranking score, with minimum value of 0 and maximum value of 6. Higher score means a worse outcome.)

Secondary Outcome Measures

Mortality
Mortality due to any cause
Modified Rankin Scale (mRS) shift analysis
(mRS is short for National Institute of health stroke scale, with minimum value of 0 and maximum value of 6. Higher score means a worse outcome.)
National Institute of Health Score Scale (NIHSS)
(NIHSS is short for modified ranking score, with minimum value of 0 and maximum value of 42. Higher score means a worse outcome.)
Thrombolysis in Cerebral Infarction (TICI) scale
TICI is for "Thrombolysis in cerebral Infarction", with minimum value of 0 and maximum value of 3. Higher score means a better reperfusion state.
Serious adverse events
Leading to death or prolonged hospitalisation
Intracranial hemorrhage
Hemorrhagic finding on CT or MRI
Quality of life assessed by questionnaire
Include but not limited to the Barthelindex of ADL, which is the abbreviation of " activities of daily living", with minimum value of 0 and maximum value of 100. Higher score means a worse outcome.
Overall costs incurred during hospitalisation
include charges and expenses of every description

Full Information

First Posted
November 21, 2022
Last Updated
February 10, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05634382
Brief Title
Endovascular Thrombectomy With and Without Intravenous Thrombolysis in Extended Time Window
Official Title
Endovascular Thrombectomy With and Without Intravenous Thrombolysis for Large Vessel Anterior Circulation Stroke in Extended Time Window
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 3, 2022 (Actual)
Primary Completion Date
November 28, 2024 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

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

5. Study Description

Brief Summary
The primary hypothesis being tested in this trial is that ischemic stroke patients in large vessel occlusion of anterior circulation at 4.5 - 9 hours post onset of stroke will have improved clinical outcomes when given endovascular thrombectomy with intravenous thrombolysis compared with that of given direct endovascular thrombectomy alone.
Detailed Description
A number of multicenter randomized controlled trials have provided evidence supporting the application of endovascular therapy for acute ischemic stroke with anterior circulation large vessel occlusion. However, whether intravenous thrombolysis is necessary before endovascular therapy is still controversial. The combined trial data (including DEVT, DIRECT-MT, MR-CLEAN NO-IV and SKIP) assessing direct mechanical thrombectomy versus bridging therapy showed no difference in improving good functional outcome. However, a recent observational cohort study of 15832 patients treated with EVT, intravenous alteplase treatment was associated with better in-hospital survival and functional outcomes after adjusting for other covariates. The 2019 AHA/ASA guidelines for the early management of patients with ischemic stroke states that mechanical thrombectomy is recommended for patients with anterior circulation large vessel occlusion within 6-24 hours of last known normal who meet the DWAN or DEFUSE-3 criteria (level I recommendation, level A evidence). The DEFUSE 3 perfusion-infarction core mismatch criteria is: core infarct volume <70mL, ischemic penumbra volume >15mL, and hypoperfusion volume/core infarct volume >1.8. Intravenous thrombolytic therapy is recommended for patients with ischemic stroke within 4.5 hours of onset. A meta-analysis of three randomized controlled trials recently published in the Lancet found that ischemic stroke at 4.5 to 9 hours of onset or wake stroke was consistent with a core infarct volume <70mL, a penumbra volume >10mL, and a hypoperfusion volume/core infarct volume >1.2. Benefit from intravenous thrombolytic therapy (3 month mRS 0-1 ratio, thrombolytic vs non-thrombolytic: 36% vs 29%). It was also strongly recommended by 2021 ESO guidelines on intravenous thrombolysis for acute ischemic stroke. For these reasons the investigators hypothesize that endovacular thrombectomy bridging with intravenous thrombolysis is superior to direct thrombectomy in patients of stroke at 4.5 to 9 hours, guided with perfusion imaging.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Acute Ischemic

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Intravenous thrombolysis bridging with endovascular thrombectomy
Arm Type
Experimental
Arm Title
Direct endovascular thrombectomy without intravenous thrombolysis
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Intravenous thrombolysis agents
Intervention Description
Intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA,alteplase) or TNK-tPA (Tenecteplase,Metalyse)
Intervention Type
Procedure
Intervention Name(s)
endovascular thrombectomy
Intervention Description
endovascular mechanical thrombectomy with nonspecific device
Primary Outcome Measure Information:
Title
Good clinical outcome
Description
Score in modified Rankin Scale (mRS) ≤ 2 (mRS is short for modified ranking score, with minimum value of 0 and maximum value of 6. Higher score means a worse outcome.)
Time Frame
90 days after randomization
Secondary Outcome Measure Information:
Title
Mortality
Description
Mortality due to any cause
Time Frame
90 days after randomization
Title
Modified Rankin Scale (mRS) shift analysis
Description
(mRS is short for National Institute of health stroke scale, with minimum value of 0 and maximum value of 6. Higher score means a worse outcome.)
Time Frame
day 0 and 90 days after randomization
Title
National Institute of Health Score Scale (NIHSS)
Description
(NIHSS is short for modified ranking score, with minimum value of 0 and maximum value of 42. Higher score means a worse outcome.)
Time Frame
day 0 and day 1 after randomization
Title
Thrombolysis in Cerebral Infarction (TICI) scale
Description
TICI is for "Thrombolysis in cerebral Infarction", with minimum value of 0 and maximum value of 3. Higher score means a better reperfusion state.
Time Frame
day 0 and day 1 after randomization
Title
Serious adverse events
Description
Leading to death or prolonged hospitalisation
Time Frame
day 0 until 90 days after randomization
Title
Intracranial hemorrhage
Description
Hemorrhagic finding on CT or MRI
Time Frame
day 1 after randomization
Title
Quality of life assessed by questionnaire
Description
Include but not limited to the Barthelindex of ADL, which is the abbreviation of " activities of daily living", with minimum value of 0 and maximum value of 100. Higher score means a worse outcome.
Time Frame
90 days after randomization
Title
Overall costs incurred during hospitalisation
Description
include charges and expenses of every description
Time Frame
90 days after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient/Legally Authorized Representative has signed the Informed Consent form Age ≥ 18 Clinical signs consistent with an acute ischemic stroke Neurological deficit with a NIHSS of ≥ 6 (deficits judged to be clearly disabling at presentation) Patient is eligible for intravenous thrombolysis Patient is eligible for endovascular treatment Randomization no later than 8 hours 45 minutes after stroke symptom onset and initiation of IV t-PA must be started within 9 hours of stroke symptoms onset (for stroke with unknown time of onset, the midpoint of the time last known to be well and symptom recognition time) ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA or CTA (including the reconstructed CTA derived from CTP). And target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml, mismatch ratio is >/= 1.8 and mismatch volume is >/= 15 ml) Core-infarct volume of Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6 based on baseline CT or MR imaging (MRI) (a region has to have diffusion abnormality in 20% or more of its volume to be considered MR-ASPECTS positive) Exclusion Criteria: Acute intracranial hemorrhage Any contraindication for IV t-PA Pre-treatment with IV t-PA Pregnancy or lactating women. A negative pregnancy test before randomization is required for all women with child-bearing potential. Known (serious) sensitivity to radiographic contrast agents, nickel, titanium metals, or their alloys Known current participation in a clinical trial (investigational drug or medical device) Renal insufficiency as defined by a serum creatinine > 2.0 mg/dl (or 176.8 µmol/l) or glomerular filtration rate (GFR) < 30 mL/min or requirement for hemodialysis or peritoneal dialysis Severe comorbid condition with life expectancy less than 90 days at baseline Known advanced dementia or significant pre-stroke disability (mRS score of ≥2) Foreseeable difficulties in follow-up due to geographic reasons (e.g. patients living abroad) Comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day). Known history of arterial tortuosity, pre-existing stent, other arterial disease and/or known disease at the femoral access site that would prevent the device from reaching the target vessel and/or preclude safe recovery after MT Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma) Radiological confirmed evidence of cerebral vasculitis CTA or MRA evidence of carotid artery dissection Evidence of additional distal intracranial vessel occlusion in another territory (i.e. A2 segment of anterior cerebral artery or M3, M4 segment of MCA) on initial NCCT/MRI or CTA/MRA
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yi Chen, Doctor
Phone
08657113588187112
Email
ileen@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Min Lou, Professor
Organizational Affiliation
Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Chen, Doctor
Email
ileen@163.com

12. IPD Sharing Statement

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Endovascular Thrombectomy With and Without Intravenous Thrombolysis in Extended Time Window

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