Study of Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core

NCT04551664 | Completed DMC

• 1 other identifier: HX-A-011(2020)
• Study Type: interventional
• Target: 456
• Locations: 1 country
• Sites: 1

Brief Summary

Endovascular therapy (EVT) was recommended as the primary treatment for patients with acute large vascular occlusion (LVO) in anterior circulation. However, the evidences of EVT for patients with large infarct volume were limited. In this study, the investigators assume that best medical management plus EVT might be superior than best medical management alone for patients who have evidence of a large infarct volume. The primary objective of the study was to establish the safety and efficacy of EVT in patients presenting with symptoms of acute ischemic stroke (AIS) from LVO in the anterior circulation and having a large infarct volume.

Conditions

Acute Ischemic Stroke

Keywords

endovascular therapy; large infarct volume

Outcome Measures

Primary Outcomes (1)

• Neurofunctional deficit defined as modified Rankin Scale (mRS)

  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

  90±7 days after randomization

Secondary Outcomes (9)

• Rate of symptomatic intracranial hemorrhage (sICH) per Heidelberg standard

  within 48 hours after randomization

• 90-day good clinical outcome

  90±14 days after randomization

• 90-day favorable clinical outcome

  90±7 days after randomization

• Dramatic recovery

  baseline, 36±12 hours after randomization

• Change of infarct volume from baseline to 36-hour (24-48 hours)

  baseline, 36±12 hours after randomization

Study Arms (2)

EVT group

EXPERIMENTAL

Patients in this group will receive best medical management plus EVT including mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty or stenting.

Drug: Best medical management; Procedure: Endovascular therapy

Best medical management group

ACTIVE COMPARATOR

Patients in this group will receive best medical management alone.

Drug: Best medical management

Interventions

Best medical management DRUG

All the patients enrolled received standard guideline-directed medical therapy including: monitor vital signs, management of blood pressure, glucose and lipids, antithrombotic (antiplatelet or anticoagulant therapy determined by treating physician) therapy if appropriate.

Best medical management group; EVT group

Endovascular therapy PROCEDURE

In the procedure, the methods including mechanical thrombectomy, aspiration thrombectomy, intra-arterial thrombolysis, angioplasty and stenting can be used according to the local interventionalists' choice. Mechanical thrombectomy (recommended with Solitaire、EMBOTRAP、Trevo or Reco revascularization device) or aspiration thrombectomy (recommended with Penumbra) will be recommended as the primary treatment.

EVT group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 80 years of age
• Presenting with symptoms consistent with an AIS
• Pre-stroke mRS score 0-1
• NIHSS score 6-30 at the time of randomization
• Randomization can be finished within 24 hours of stroke onset (stroke onset time is defined as last known well time)
• CTA or MRA proved occlusion of Internal Carotid Artery (ICA) terminal or M1 segment of Middle Cerebral Artery
• Combination of NCCT ASPECTS and perfusion core volume when ASPECTS \<3 or \> 5 (6h-24h). Imaging evidence of low ASPECTS (based on NCCT) or large infarct Core (defined as rCBF \<30% on CT perfusion or ADC\<620 on MRI) filling one of the following criteria:
• ASPECTS 3-5
• ASPECTS \>5 (6h-24h) with infarct core volume 70-100 ml
• ASPECTS \<3 with infarct core volume 70-100 ml

You may not qualify if:

• Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;
• Known severe allergy (more than a rash) to contrast media uncontrolled by medications;
• Refractory hypertension (defined as persistent systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg);
• Known hemorrhagic tendency (including but not limited to): Baseline platelet count \<100×109/L; Heparin was administered within 48 hours with APTT≥35s; on anticoagulant therapy with warfarin and International Normalized Ratio (INR) \> 1.7 (Patients with no history or suspected coagulopathy do not need to wait for laboratory results of INR or APTT prior to enrollment)
• Parenchymal organ surgery and biopsy were performed in the past one month
• Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past one month
• Undergoing hemodialysis or peritoneal dialysis; Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or serum creatinine \>220 mmol/L (2.5mg/dl)
• Brain tumor (with mass effect)
• The expected survival time is less than 1 year (such as complicated with malignant tumor, serious heart and lung diseases, etc.)
• Participation in other interventional randomized clinical trials that may confound outcome assessment of the trial
• Other circumstances that the investigator considers inappropriate for participation in the trial or that may pose significant risks to patients (such as inability to understand and/or follow the study procedures and/or follow up due to mental disorders, cognitive or emotional disorders)
• Midline shift, herniation or mass effect with effacement of the ventricles
• Evidence of acute intracranial hemorrhage
• Acute bilateral strokes or multiple intracranial vessels occlusions

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100010, China

Location

Related Publications (15)

• Wang Z, Liu C, Wang M, Cai S, Nie X, Liu L, Huo X, Pan Y, Miao Z, Wang Y; ANGEL-ASPECT Study Group. White matter lesions modifying endovascular therapy outcomes in large ischemic core stroke: A secondary analysis of the ANGEL-ASPECT trial. Chin Med J (Engl). 2026 Feb 4. doi: 10.1097/CM9.0000000000003993. Online ahead of print.

  PMID: 41641580 DERIVED

• Gan Y, Song S, Zhang D, Chen F, He J, Guan Z, Tu K, Yu Z, Pan Y, Miao Z, Mo D, Tong X. Machine learning models for predicting futile recanalisation after endovascular treatment in patients with large core infarction. Stroke Vasc Neurol. 2026 Jan 29:svn-2025-004258. doi: 10.1136/svn-2025-004258. Online ahead of print.

  PMID: 41611344 DERIVED

• Zhang L, Liu Y, Chen F, Zhu H, Abdalkader M, Sun Y, Sun D, Nguyen T, Zhang Y, Miao Z; ANGEL-ASPECT Study Group. Factors associated with infarct volume growth after mechanical thrombectomy in large core infarction: ANGEL-ASPECT insights. Stroke Vasc Neurol. 2026 Jan 21:svn-2025-004774. doi: 10.1136/svn-2025-004774. Online ahead of print.

  PMID: 41565354 DERIVED

• Chen J, Nie X, Wang M, Zhang D, Sun D, Pan Y, Huo X, Li Z, Miao Z; ANGEL-ASPECT Study Group. Time-Dependent Impact of Mismatch Profiles on Outcomes Following Endovascular Thrombectomy for Large Ischemic Stroke. Stroke. 2025 Dec 24. doi: 10.1161/STROKEAHA.125.052698. Online ahead of print.

  PMID: 41439308 DERIVED

• Li K, Sun D, Wang M, Pu S, Pan Y, Abdalkader M, Liu F, Chen C, Sun P, Yu J, Huo X, Nguyen TN, Miao Z, Han J; ANGEL-ASPECT Investigators. Significance of occlusion site on outcomes in stroke patients with large infarction undergoing endovascular therapy: A prespecified subgroup analysis of the ANGEL-ASPECT trial. Int J Stroke. 2025 Nov 29:17474930251393014. doi: 10.1177/17474930251393014. Online ahead of print.

  PMID: 41317114 DERIVED

• Huo X, Sun D, Nguyen TN, Ma G, Pan Y, Tong X, Yuan G, Han H, Chen W, Wei M, Zhang J, Zhou Z, Yao X, Song W, Cai X, Nan G, Li D, Wang AY, Ling W, Cai C, Wen C, Wang E, Zhang L, Jiang C, Liao G, Chen X, Li T, Liu S, Li J, Sun Y, Xu N, Gao Z, Ju D, Song C, Zhou F, Shi Q, Luo J, Liu Y, Guo Z, Zheng H, Dai L, Zhao J, Geng X, Tang Y, Yin C, Yang H, Zhang X, Li S, Abdalkader M, Gao F, Ma N, Mo D, Ren Z, Liu L, Wang Y, Miao Z; ANGEL-ASPECT Investigators. Endovascular Therapy Versus Medical Management for Large Ischemic Infarct: 1-Year Outcomes of the ANGEL-ASPECT Trial. Stroke. 2025 Sep;56(9):2398-2407. doi: 10.1161/STROKEAHA.124.050086. Epub 2025 Aug 25.

  PMID: 40854041 DERIVED

• Sun D, Guo X, Ling L, Jiao L, Nguyen TN, Abdalkader M, Pan Y, Wang M, Luo G, Jia B, Tong X, Ma N, Gao F, Mo D, Raynald, Huo X, Miao Z; ANGEL-ASPECT Study Group. Sex-Related Differences in Endovascular Treatment Outcomes for Acute Large Infarcts: The ANGEL-ASPECT Subanalysis. Stroke. 2025 Aug;56(8):2033-2042. doi: 10.1161/STROKEAHA.124.050025. Epub 2025 May 9.

  PMID: 40340582 DERIVED

• Shi Z, Luo G, Huo X, Sun D, Pan Y, Wang M, Ai T, Song L, Li X, Jia B, Wang B, Zhang L, Chen F, Sun Y, Mo D, Gao F, Ma N, Miao Z; ANGEL-ASPECT Study Group. Predictors of parenchymal hemorrhage after endovascular treatment in large core ischemic stroke: a post-hoc analysis of the ANGEL-ASPECT trial. J Neurointerv Surg. 2025 Apr 25:jnis-2025-023285. doi: 10.1136/jnis-2025-023285. Online ahead of print.

  PMID: 40280761 DERIVED

• Lu Q, Zheng L, Nie X, Wang M, Duan W, Liu X, Zhang Z, Wen M, Yang Z, Leng X, Pan Y, Nguyen TN, Liu L. Clinical Severity and Outcomes in Large Infarcts With Endovascular Therapy: A Post Hoc Analysis of the ANGEL-ASPECT Trial. Stroke. 2025 Apr;56(4):1048-1053. doi: 10.1161/STROKEAHA.124.049315. Epub 2025 Feb 27.

  PMID: 40013350 DERIVED

• Yuan G, Sang H, Nguyen TN, Huo X, Pan Y, Wang M, Qiu Z, Liu L, Xia H, Wu J, Long C, Xu J, Huang F, He B, Wu D, Wang H, Feng C, Liang Y, Zhou X, Yang W, Huang Z, Xiang Y, Lei L, Saver JL, Miao Z, Cai X. Association Between Time to Treatment and Outcomes of Endovascular Therapy vs Medical Management in Patients With Large Ischemic Stroke. Neurology. 2025 Jan 14;104(1):e210133. doi: 10.1212/WNL.0000000000210133. Epub 2024 Dec 9.

  PMID: 39652807 DERIVED

• Zhang L, Chen F, Nguyen TN, Pan Y, Liu Y, Wang M, Li S, Sun D, Huo X, Jia B, Miao Z; ANGEL-ASPECT Study Group. Spontaneous recanalization in acute large core ischemic stroke due to large vessel occlusion: a post-hoc analysis of the ANGEL-ASPECT trial. J Neurointerv Surg. 2025 Dec 17;18(1):91-98. doi: 10.1136/jnis-2024-022357.

  PMID: 39332900 DERIVED

• Liang F, Zhang K, Wu Y, Wang X, Hou X, Yu Y, Wang Y, Wang M, Pan Y, Huo X, Han R, Miao Z. Anaesthesia modality on endovascular therapy outcomes in patients with large infarcts: a post hoc analysis of the ANGEL-ASPECT trial. Stroke Vasc Neurol. 2025 Apr 29;10(2):e003320. doi: 10.1136/svn-2024-003320.

  PMID: 39160092 DERIVED

• Zheng L, Nie X, Wang M, Liu X, Duan W, Zhang Z, Liu J, Wei Y, Wen M, Yang Z, Leung TW, Ma G, Huo X, Pan Y, Nguyen TN, Leng X, Miao Z, Liu L; ANGEL-ASPECT Investigators. Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial. EClinicalMedicine. 2024 Apr 12;72:102595. doi: 10.1016/j.eclinm.2024.102595. eCollection 2024 Jun.

  PMID: 38638180 DERIVED

• Sun D, Guo X, Nguyen TN, Pan Y, Ma G, Tong X, Raynald, Wang M, Ma N, Gao F, Mo D, Huo X, Miao Z; ANGEL-ASPECT Study Group. Alberta Stroke Program Early Computed Tomography Score, Infarct Core Volume, and Endovascular Therapy Outcomes in Patients With Large Infarct: A Secondary Analysis of the ANGEL-ASPECT Trial. JAMA Neurol. 2024 Jan 1;81(1):30-38. doi: 10.1001/jamaneurol.2023.4430.

  PMID: 38010691 DERIVED

• Huo X, Ma G, Tong X, Zhang X, Pan Y, Nguyen TN, Yuan G, Han H, Chen W, Wei M, Zhang J, Zhou Z, Yao X, Wang G, Song W, Cai X, Nan G, Li D, Wang AY, Ling W, Cai C, Wen C, Wang E, Zhang L, Jiang C, Liu Y, Liao G, Chen X, Li T, Liu S, Li J, Gao F, Ma N, Mo D, Song L, Sun X, Li X, Deng Y, Luo G, Lv M, He H, Liu A, Zhang J, Mu S, Liu L, Jing J, Nie X, Ding Z, Du W, Zhao X, Yang P, Liu L, Wang Y, Liebeskind DS, Pereira VM, Ren Z, Wang Y, Miao Z; ANGEL-ASPECT Investigators. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. N Engl J Med. 2023 Apr 6;388(14):1272-1283. doi: 10.1056/NEJMoa2213379. Epub 2023 Feb 10.

  PMID: 36762852 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Zhongrong Miao, MD, PhD

  Beijing Tiantan Hospital, Capital Medical Univerity

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of interventional neurology

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 16, 2020
• Study Start: October 2, 2020
• Primary Completion: August 15, 2022
• Study Completion: May 30, 2023
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)