Efficacy and Safety of Bailout Intracranial Angioplasty or Stenting After Thrombectomy for Acute Intracranial Atherosclerotic Large Vessel Occlusion (ANGEL-REBOOT 2)

Official title

Efficacy and Safety of Bailout Intracranial Angioplasty or Stenting After Thrombectomy for Acute Intracranial Atherosclerotic Large Vessel Occlusion: A Clinical Trial Combining a Randomized Controlled Trial and a Concurrent Prospective Observational Cohort

Overview

A multicenter, randomized, open-label, blinded-endpoint trial with a concurrent prospective observational cohort to compare bailout intracranial angioplasty or stenting versus standard therapy on functional outcome, stroke recurrence, and mortality in patients with acute intracranial atherosclerotic stenosis-related large vessel occlusion after thrombectomy.

Detailed description

This is a clinical trial with a composite design, consisting of: (1) a multicenter, prospective, open-label, blinded-endpoint randomized controlled trial (RCT) for patients with successful recanalization but residual severe stenosis (\>70%) after thrombectomy, and (2) a concurrent prospective observational cohort for patients with failed recanalization. Patients with acute ischemic stroke due to intracranial atherosclerotic stenosis-related large vessel occlusion (ICAS-LVO) within 24 hours of symptom onset who undergo up to two thrombectomy passes are assessed. Those achieving successful recanalization (expanded Thrombolysis in Cerebral Infarction \[eTICI\] grade ≥2b) but with residual stenosis ≥70% are enrolled in the RCT and randomly assigned in a 1:1 ratio to receive either bailout angioplasty or stenting (BAOS) (intervention group) or standard therapy (control group). Randomization is performed using a centralized interactive web response system with a minimization method, stratified by baseline National Institutes of Health Stroke Scale score (6-15 vs. ≥16), time from symptom onset to puncture (≤6 hours vs. 6-24 hours), and occlusion site (anterior circulation vs. posterior circulation). For patients who fail to achieve successful recanalization (eTICI 0-2a) after at least two thrombectomy passes, they are enrolled in the concurrent prospective observational cohort without randomization, and subsequent treatment (including continued thrombectomy, BAOS, or termination of the procedure) is at the discretion of the treating physician. The primary endpoint is the modified Rankin Scale (mRS) score at 90 days (±7 days) after randomization or enrollment. Key secondary efficacy endpoints include the proportion of patients with mRS scores of 0-1, 0-2, and 0-3 at 90 days; stroke recurrence in the target vessel territory within 90 days and 1 year; NIHSS score at 24 hours; and quality of life measures at 90 days and 1 year. Safety endpoints include symptomatic intracranial hemorrhage within 24 hours (defined by the Heidelberg Bleeding Classification), any intracranial hemorrhage within 24 hours, mortality at 7 days, 90 days, and 1 year, and procedure-related complications (e.g., arterial perforation, dissection, or distal embolization). Follow-up assessments are performed at 24 hours, 7 days or discharge (whichever occurs first), 90 days, and every 3 months thereafter until 1 year after randomization or enrollment.

Interventions

• Procedure Bailout Intracranial Angioplasty or Stenting
  Balloon angioplasty and/or stent placement for residual severe stenosis (≥70%) after successful thrombectomy; combined with medical management (intravenous tirofiban, followed by dual antiplatelet therapy with aspirin 100 mg/day and clopidogrel 75 mg/day for 90 days, then single antiplatelet therapy thereafter; and cerebrovascular risk factor management).
• Procedure Standard Thrombectomy
  Endovascular thrombectomy performed according to guideline recommendations, without additional endovascular intervention; combined with medical management (intravenous tirofiban as needed, dual antiplatelet therapy with aspirin 100 mg/day and clopidogrel 75 mg/day for 90 days, then single antiplatelet therapy thereafter; and cerebrovascular risk factor management).

Primary outcome measures

• The primary endpoint is the mRS score at 90 (±7) days after randomization (or after enrollment), analyzed as an ordinal variable [Time frame: 90±7 days after randomization (or after enrollment)]

Secondary outcome measures (10)

• The proportion of mRS 0-1, 0-2 and 0-3 at 90 (±7) days [Time frame: 90±7 days after randomization (or after enrollment)]
• The rate of stroke recurrence in the target vessel territory within 90 (±7) days [Time frame: 90±7 days after randomization (or after enrollment)]
• NIHSS score at 24 (±6/+12) hours [Time frame: 24 (-6/+12) hours after randomization (or after enrollment)]
• European Five Dimensional Health Scale Level 5 (EQ-5D-5L) score at 90±7 days [Time frame: 90±7 days after randomization (or after enrollment)]
• Patency of the target vessel at 24 (±6/+12) hours after the procedure, as confirmed by CTA, MRA, DSA, or TCD [Time frame: 24 (-6/+12) hours after randomization (or after enrollment)]
• The mRS score at 1 year (±30 days), analyzed as an ordinal variable [Time frame: 1 year (±30 days) after randomization (or after enrollment)]
• The proportion of mRS 0-1, 0-2 and 0-3 scores at 1 year (± 30 days) [Time frame: 1 year (±30 days) after randomization (or after enrollment)]
• The rate of stroke recurrence in the target vessel territory within 1 year (± 30 days) [Time frame: 1 year (±30 days) after randomization (or after enrollment)]
• Patency of the target vessel at 1 year (± 30 days) after the procedure, as confirmed by CTA, MRA, DSA, or TCD [Time frame: 1 year (±30 days) after randomization (or after enrollment)]
• European Five Dimensional Health Scale Level 5 (EQ-5D-5L) score at 1 year (±30 days) [Time frame: 1 year (±30 days) after randomization (or after enrollment)]

Eligibility criteria

Inclusion criteria

• Age≥18 years.
• Time interval from symptom onset to puncture ≤24 hours.
• National Institute of Health Stroke Scale (NIHSS) Score ≥6 before randomisation.
• Pre-stroke modified Rankin Scale (mRS) of 0-2.
• Each patient or their legal representative must provide written informed consent before enrolment.

Imaging Inclusion Criteria:

• For patients with anterior circulation stroke, a CT or DWI-based Alberta Stroke Program Early CT Score (ASPECTS) of ≥6 is required.
• For patients with posterior circulation stroke, CT or DWI-based posterior circulation ASPECTS (pc-ASPECTS) of ≥6 and Pons-Midbrain Index (PMI) of <3 are required.

Angiographic Inclusion Criteria:

• Acute ischemic stroke (AIS) resulting from large vessel occlusion (LVO) involving the intracranial internal carotid artery, the M1 segment of the middle cerebral artery, the V4 segment of the vertebral artery, or the basilar artery, with high suspicion of intracranial atherosclerotic stenosis-related large-vessel occlusion (ICAS-LVO).
• Part 1 (RCT): Successful recanalization of the occluded artery (eTICI ≥ 2b) with residual stenosis ≥ 70% after 1-2 thrombectomy attempts.

Part 2 (Prospective observational cohort): Failure to achieve successful recanalization (eTICI 0-2a) after at least two thrombectomy attempts. All other inclusion criteria are identical to those for Part 1.

• Occluded artery amenable to angioplasty (balloon dilation and/or stenting) by the judgement of the treating neurointerventionalist.

Exclusion criteria

• Any sign of intracranial hemorrhage (ICH, except microbleeds) on baseline brain imaging.
• CT or MR imaging evidence of intracranial tumor (except small meningiomas or cerebral aneurysms < 3mm in diameter).
• Any indication of intracranial vessel perforation during thrombectomy..
• Presence of tandem lesion in the extracranial segment of the internal carotid artery or vertebral artery, or intracranial arterial stenosis with distal vessel occlusion..
• Stenosis caused by non-atherosclerotic intracranial arteriopathies (e.g., autoimmune vasculitis, vasospasm, cerebral artery dissection).
• Evidence of cardioembolism (e.g., atrial fibrillation, prosthetic heart valve, infective endocarditis, mitral stenosis, atrial myxoma, intracardiac thrombus/vegetation, left ventricular aneurysm, etc.).
• Contraindication for antiplatelet treatment.
• Excessive vascular tortuosity or anatomical variants that may preclude successful delivery or positioning of interventional devices.
• History of contraindication to the use of contrast medium.
• Refractory hypertension (defined as systolic blood pressure>185 mmHg or diastolic blood pressure>110 mmHg) that cannot be controlled by drug treatment.
• Known hereditary or acquired bleeding tendency, lack of coagulation factors, or oral anticoagulants with INR>1.5.
• Blood glucose<2.8 or>22.2 mmol/L; Platelet count<100\*109/L, serum creatinine>2.0 g/L (177 μ mol/L), or glomerular filtration rate<30 ml/(min\*1.73 m2).
• Concurrent participation in another drug or device trial, or expected participation within the following 3 months.
• Patients whose life expectancy is less than 1 year (such as patients with malignant tumor, advanced cardiopulmonary disease, etc.).
• Known pregnancy or lactation, or positive pregnancy test before randomization (or before enrollment).
• Known dementia or psychiatric disorder that precludes completion of neurological assessments and follow-up.
• Any other condition deemed by the site investigator to make the patient unsuitable for participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07618052 · HX-A-2026023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗