ANGEL-REBOOT: Randomized Study of Bailout Intracranial Angioplasty for Unsuccessful Thrombectomy
Study Details
Study Description
Brief Summary
Unfavorable outcomes were associated with failed recanalization of acute large vessel occlusions (LVO). The failed recanalization rate of mechanical thrombectomy (MT) was 12-41% reported in multiple randomized controlled trials (RCT). Possible reasons of failed recanalization included technical failure of access, failure of retrieving thrombus, thrombotic re-occlusion, and pre-existing intracranial atherosclerotic stenosis (ICAS). Several studies have been published on balloon dilation or permanent stenting as rescue approaches for failed thrombectomy in individual cases, but there is no evidence from RCTs regarding this topic. ANGEL-REBOOT aims to close this gap by performing a randomized study of bailout intracranial angioplasty (balloon dilation and/or stenting) for unsuccessful thrombectomy in LVO patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
The ANGEL-REBOOT is a multicentered, prospective, randomized, open-label, blinded end-point (PROBE) study. A total of approximately 348 patients within 8 hours of symptom onset of acute ischemic stroke (NIHSS：6-30) , who has the imaging evidence of an occlusion of intracranial internal cerebral artery (ICA)，M1 of the middle cerebral artery (MCA)，V4 of vertebral artery（VA) or basilar artery (BA) segment, anterior circulation stroke [defined as: NECT or DWI ASPECTS≥6] or posterior circulation stroke [defined as: CTA-SI or DWI pc-ASPECTS≥6 and Pons-Midbrain Index (PMI)<3].
Randomization would take place after failed recanalization after 1-3 attempts（traget vessel eTICI 0-2a) thrombectomy with stent retriever and/or contact aspiration. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two groups after offering informed content.
If the patient is randomized into the bailout angioplasty arm, the choice of balloon dilation or stenting will be left to the discretion of the interventionalist.
If the patient is randomized into the thrombectomy alone arm, the interventionalist will decide whether to stop the endovascular recanalization procedure or to perform further recanalization attempts using stent-retrievers and/or aspiration catheters.
The primary objective is to compare the efficacy and safety of bailout intracranial angioplasty with MT alone following unsuccessful recanalization by MT in acute LVO patients.
The study consists of three visits including 24 hours after treatment, 7 days or discharge, and 90 days. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the study. The primary endpoint is the modified Rankin's scale (mRS) at 90 days. The study is anticipated to last from October 2021 to March 2024 with 348 participants recruited form about 40 centers in China. All the related investigative organization and individuals will obey the Declaration of Helsinki and Chinese Good Clinical Practice standard. A scheduled Data and Safety Monitoring Board (DSMB) meeting will oversight the safety data of the study. The trial has been approved by Institutional Review Board (IRB) and Ethics Committee (EC) in Being Tiantan hospital, Capital Medical University.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: bailout angioplasty If the patient is randomized into the bailout angioplasty arm, the choice of balloon dilation or stenting will be left to the discretion of the interventionalist. |
Procedure: Bailout angioplasty
It is recommended to use FocuStar (Hemo, China) for balloon dilation and Winspan or Neuroform EZ (Stryker, USA) for stenting.
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| Active Comparator: thrombectomy alone If the patient is randomized into the thrombectomy alone arm, the interventionalist will decide whether to stop the endovascular recanalization procedure or to perform further recanalization attempts using stent-retrievers and/or aspiration catheters. Balloon dilation and/or stenting procedure after randomization should be avoided in the thrombectomy alone arm. |
Procedure: thrombectomy alone
stop the endovascular recanalization procedure or to perform further recanalization attempts using stent-retrievers and/or aspiration catheters.
|
Outcome Measures
Primary Outcome Measures
- Clinical outcome 90 (±14) days after stroke on the modified Ranking Score (mRS) as an ordinal scale (shift analysis) [90±14 days after randomization]
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms. Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead
Secondary Outcome Measures
- Rate of Good functional outcome (mRS 0-2) at 90 (±14) days after stroke [90±14 days after randomization]
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms. Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead
- Functional health status and quality of life (EQ-5D-5L) at 90 (±14) days after stroke [90±14 days after randomization]
EQ-5D-5L is a standardized instrument for measuring generic health status. Rated level can be coded as a number 1, 2, 3, 4 or 5, which indicates having no problems for 1, having some problems for 2, having moderate problems for 3, having serious problems for 4 and having extreme problems for 5.
- Technical success defined as successful recanalization (eTICI 2b-3) of the occluded vessel at the end of the procedure [the end of the procedure]
In brief, eTICI grade 0 is equivalent to no reperfusion or 0% filling of the downstream territory; eTICI 1 reflects thrombus reduction without any reperfusion of distal arteries; eTICI 2a is reperfusion in less than half or 1-49% of the territory; eTICI 2b50 is 50-66% reperfusion, exceeding the modified TICI (mTICI) 2B threshold but below the original TICI 2B cut-off point; eTICI 2b67 is 67-89% reperfusion, exceeding TICI but below TICI 2C; eTICI 2c is equivalent to TICI 2C or 90-99% reperfusion; and eTICI 3 is complete or 100% reperfusion, tantamount to TICI 3.
- Infarct volume on FLAIR/T2WI or NECT after 18-36 hours of treatment [18-36 hours after treatment]
The infarct volume is determined on FLAIR or T2-weighted MRI (preferred) or unenhanced CT if MRI is not feasible.
- Frequency of residual stenosis > 50% on DSA at the end of the procedure [the end of the procedure]
Warfarin-Aspirin Symptomatic Intracranial Disease method, calculate vessel stenosis by the formula: percent stenosis = [1 - (D_stenosis/D_normal)] × 100, where D_stenosis = the diameter of the artery at the site of the most severe stenosis, and D_normal = the diameter of the normal segment of the artery.
- NIHSS score at 24 hours after treatment [24 hours after treatment]
The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient.
- Proportion of target vessel recanalization at 18-36 hours [18-36 hours after treatment]
Target vessel recanalization defined as successful recanalization (eTICI 2b-3) .
- Symptomatic intracranial hemorrhage (SICH) defined as the Heidelberg classification within 18-36 hours of treatment [18-36 hours after treatment]
Heidelberg standard was defined as new intracranial hemorrhage detected by brain imaging associated with any of the item below: 4 points total NIHSS at the time of diagnosis compared to immediately before worsening. 2 point in one NIHSS category. Leading to intubation/hemicraniectomy/ventricular drainage placement or other major medical/surgical intervention. Absence of alternative explanation for deterioration.
- Severe procedure-related complications (e.g. dissection of intracranial artery) [90±14 days after randomization]
Severe procedure-related complications (e.g. dissection of intracranial artery)
- Ischemic stroke in downstream territory of the occluded vessel within 90 (±14) days after stroke [90±14 days after randomization]
Ischemic stroke in downstream territory of the occluded vessel within 90 (±14) days after stroke
- Parenchymal hemorrhage type 2 (PH-2) after 18-36 hours [18-36 hours after treatment]
Parenchymal hemorrhage type 2 (PH-2) after 18-36 hours
- Infarct in new territories (INT) within 18-36 hours [18-36 hours after treatment]
INT is classified based on two parameters: size (types I, II, and III) and catheter manipulation across territory ostium (types A and B). Thus an INT may be classified as IA, IIB, etc. Classification of INT based on size: Type I : ≤2 mm diffusion lesion (unidentifiable on non-contrast CT scan). Type II : >2 mm to ≤20 mm lesion (could potentially be difficult to identify on CT scan). Type III : Large (>20 mm) infarct in new territory. Classification of INT based on catheter manipulation across territory ostium: Type A : Catheter was manipulated past the ostium of the new territory (eg, large ACA infarct in a patient who originally had an M1 occlusion): increased likelihood infarct is related to procedure. Type B : Catheter was not manipulated past the ostium of the new territory (eg, left PICA infarct in a patient who originally had a right M1 occlusion): decreased likelihood infarct is related to procedure.
- Mortality within 90 (±14) days after stroke [90±14 days after randomization]
Mortality within 90 (±14) days after stroke
- Death or dependency (mRS 4-6) at 90 (±14) days after stroke [90±14 days after randomization]
Death or dependency (mRS 4-6) at 90 (±14) days after stroke
Eligibility Criteria
Criteria
Inclusion Criteria:
- Clinical Inclusion criteria
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Age ≥18 years
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Pre-stroke mRS 0~2
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Acute ischemic stroke (NIHSS score 6-30)
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Time-last-known-well to puncture ≤ 8 hours
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Informed consent
- Baseline Imaging Inclusion Criteria
1.Anterior circulation stroke: NECT or DWI ASPECTS ≥ 6; Posterior circulation stroke: CTA-SI or DWI pc-ASPECTS ≥ 6 and Pons-Midbrain Index (PMI) < 3
- Angiographic Inclusion Criteria
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Acute ischemic stroke caused by LVO, including intracranial internal cerebral artery (ICA)，M1 of the middle cerebral artery (MCA)，V4 of vertebral artery（VA) or basilar artery (BA)
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Failed recanalization (eTICI 0-2a) after 1-3 attempts of thrombectomy with stent retriever and/or contact aspiration
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Microcatheter can pass through the occluded segment before randomization
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Occluded artery amenable to angioplasty by judgement of the treating neurointerventionalist
Exclusion Criteria:
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Any sign of intracranial hemorrhage on brain imaging prior to thrombectomy
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CT or MRI evidence of mass effect or intracranial tumor
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Any sign of intracranial vessel perforation during mechanical thrombectomy prior to randomization
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Contraindication of anti-platelet treatment
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History of contraindication for contrast medium
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Current use of oral anticoagulants (e.g. INR > 1.7 for Vitamin K antagonists)
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Current pregnant or breast-feeding
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Known to have dementia or psychiatric disease unable to complete neurological assessment and follow-up
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Life expectancy is less than 3 months
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Enrolled in another drug or device trial or expected to participate in another drug or device treatment trial within the following 3 months.
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Any other condition (in the opinion of the site investigator) that inappropriate to participate this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tiantan Hospital | Beijing | Beijing | China | 100010 |
Sponsors and Collaborators
- Beijing Tiantan Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HA-X-026(2020)