Clinical trial NCT05122286: Randomized Study of Bailout Intracranial Angioplasty Following Thrombectomy for Acute Large Vessel Occlusion
Official title: Randomized Study of Bailout Intracranial Angioplasty Following Thrombectomy for Acute Large Vessel Occlusion: A Multi-centered, Prospective, Open-label, Blind Endpoint, Randomized Controlled Trial (ANGEL-REBOOT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Endovascular treatment
Large vessel occlusion
Angioplasty
Thrombectomy
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2021-11-16
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Unfavorable outcomes were associated with failed thrombectomy of acute large vessel occlusions (LVO). The failed thrombectomy rate was 12-41% reported in multiple randomized controlled trials (RCT). Possible reasons of failed thrombectomy 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.

Detailed description: The ANGEL-REBOOT is a multicentered, prospective, randomized, open-label, blinded end-point (PROBE design) study. A total of approximately 348 patients within 24 hours of symptom onset of acute ischemic stroke (NIHSS≥6), who has the imaging evidence of anterior circulation stroke (CT or DWI ASPECTS≥6) or posterior circulation stroke (CT or DWI pc-ASPECTS≥6 and Pons-Midbrain Index \[PMI\]\<3) caused by an occlusion of intracranial internal cerebral artery (ICA), M1 segment of middle cerebral artery (MCA), V4 segment of vertebral artery (VA) or basilar artery (BA).

Randomization would take place after failed thrombectomy (defined as eTICI 0-2a or a remaining high-grade stenosis \> 70% after 1-3 attempts of 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 (bailout angioplasty or standard therapy) 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 standard therapy 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 standard therapy following unsuccessful thrombectomy in acute LVO patients.

The study consists of three visits including 24 hours, 7 days or discharge, and 90 days after randomization. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment and neurological function scale will be recorded during the study. The primary endpoint is the modified Ranking Scale (mRS) at 90 days. The study is anticipated to last from December 2021 to September 2023 with 348 participants recruited form about 40 centers in China. All the related investigative organization and individuals will obey the Declaration of Helsinki and regulation of Chinese Good Clinical Practice. A scheduled Data and Safety Monitoring Board (DSMB) meeting will oversight the safety and data quality of the study. The trial has been approved by Institutional Review Board (IRB) and Ethics Committee (EC) in Beijing Tiantan hospital, Capital Medical University.

Eligibility criteria: Inclusion Criteria:

* Clinical Inclusion criteria

  1. Age ≥18 years
  2. Pre-stroke mRS 0\~2
  3. Acute ischemic stroke (NIHSS ≥ 6)
  4. Time-last-known-well to puncture ≤ 24 hours
  5. Informed consent
* Baseline Imaging Inclusion Criteria

  1.Anterior circulation stroke: CT or DWI ASPECTS ≥ 6; Posterior circulation stroke: CT or DWI pc-ASPECTS ≥ 6 and Pons-Midbrain Index (PMI)\<3
* Angiographic Inclusion Criteria

  1. 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)
  2. Failed recanalization (eTICI 0-2a) or residual severe stenosis (\> 70%) after 1-3 attempts of thrombectomy with stent retriever and/or contact aspiration
  3. Microcatheter can pass through the occluded segment before randomization
  4. Occluded artery amenable to angioplasty by judgement of the treating neurointerventionalist

Exclusion Criteria:

1. Any sign of intracranial hemorrhage on brain imaging prior to thrombectomy
2. CT or MRI evidence of mass effect or intracranial tumor
3. Any sign of intracranial vessel perforation during mechanical thrombectomy prior to randomization
4. Contraindication of anti-platelet treatment
5. History of contraindication for contrast medium
6. Current use of oral anticoagulants (e.g. INR \> 1.7 for Vitamin K antagonists)
7. Current pregnant or breast-feeding
8. Known to have dementia or psychiatric disease unable to complete neurological assessment and follow-up
9. Life expectancy is less than 3 months
10. Enrolled in another drug or device trial or expected to participate in another drug or device treatment trial within the following 3 months.
11. Any other condition (in the opinion of the site investigator) that inappropriate to participate this study

Primary outcomes:
measure: Clinical outcome 90 (±14) days after randomization on the modified Ranking Score (mRS) as an ordinal scale (shift analysis)
timeFrame: 90±14 days after randomization
Secondary outcomes:
measure: Rate of good functional outcome (mRS 0-2) at 90 (±14) days after randomization
timeFrame: 90±14 days after randomization
measure: Rate of independent ambulation (mRS 0-3) at 90 (±14) days after randomization
timeFrame: 90±14 days after randomization
measure: Functional health status and quality of life (EQ-5D-5L) at 90 (±14) days after randomization
timeFrame: 90±14 days after randomization
measure: Technical success defined as successful recanalization (eTICI 2b-3) of the occluded vessel at the end of the procedure
timeFrame: The end of the procedure
measure: Infarct volume on FLAIR/T2WI or CT after 18-36 hours of randomization
timeFrame: 18-36 hours after randomization
measure: NIHSS score at 24 hours after randomization
timeFrame: 24 hours after randomization
measure: Proportion of target vessel recanalization at 18-36 hours after randomization
timeFrame: 18-36 hours after randomization
measure: Symptomatic intracranial hemorrhage (SICH) defined as the Heidelberg classification within 18-36 hours of randomization
timeFrame: 18-36 hours after randomization
measure: Severe procedure-related complications (e.g. dissection of intracranial artery)
timeFrame: 90±14 days after randomization
measure: Recurrence of ischemic stroke in downstream territory of the occluded vessel within 90 (±14) days after randomization
timeFrame: 90±14 days after randomization
measure: Parenchymal hemorrhage type 2 (PH-2) after 18-36 hours of randomization
timeFrame: 18-36 hours after randomization
measure: Infarct in new territories (INT) within 18-36 hours of randomization
timeFrame: 18-36 hours after randomization
measure: Mortality within 90 (±14) days after randomization
timeFrame: 90±14 days after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Zhongrong Miao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tiantan Hospital
name: Feng Gao, MD
role: PRINCIPAL_INVESTIGATOR
References: