Endovascular Treatment for eXtra-Large Ischemic Stroke (XL STROKE-2)

Efficacy and Safety of Endovascular Thrombectomy Plus Medical Management Versus Medical Management Alone in Acute Ischemic Stroke Patients With Large Vessel Occlusion and Extra-Large Infarct Core: A Multicenter, Randomized Controlled Trial

The role of endovascular thrombectomy in patients with extra-large ischemic burden is still unclear. The XL STROKE-2 randomized trial is aiming to investigate the efficacy and safety of mechanical thrombectomy in acute extra-large ischemic stroke patients with large vessel occlusion.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute Ischemic
• Intervention / Treatment: Drug: Medical management; Procedure: Endovascular thrombectomy

Detailed Description

Several randomized trials have shown that endovascular thrombectomy improve functional outcomes in acute ischemic stroke patients with large vessel occlusion. Recently, six randomized controlled trials demonstrated the efficacy and safety of endovascular thrombectomy for large infarct patients (defined as Alberta Stroke Program Early Computed Tomography Score [ASPECTS] ≥3 or infarct core <100ml). Patients with extra-large infarct core (volume greater than 100 mL, ASPECTS score of 0 to 2) accounted for a small proportion of these trials. Therefore, the role of endovascular thrombectomy in patients with extra-large ischemic burden is still unclear. That is to say, exactly where the lower limit of endovascular thrombectomy is unknown. The XL STROKE-2 randomized trial is aiming to investigate the efficacy and safety of mechanical thrombectomy in acute extra-large ischemic stroke patients with large vessel occlusion.

• Study Type: Interventional
• Enrollment (Estimated): 286
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhongfan Ruan; Phone Number: 15616320002; Email: ruanzhongfan@sina.com
• Study Contact Backup: Name: Zhongming Qiu; Phone Number: 13236599269; Email: qiuzhongmingdoctor@163.com

Study Locations

• China
  • Hunan
    • Hengyang, Hunan, China
      • Recruiting
      • The First Affiliated Hospital, Hengyang Medical School, University of South China
      • Contact: Zhongfan Ruan; Email: ruanzhongfan@sina.com
    • Xiangtan, Hunan, China, 421001
      • Recruiting
      • Xiangtan Central Hospital
      • Contact: Guangxiong Yuan; Phone Number: 18973223018; Email: yuanguangxiong74@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older, and modified Rankin scale score = 0 or 1 in patients 80 years or older;
2. Acute ischemic stroke within 6 hours from last known well to randomization, or with negative MRI-FLAIR (no change on FLAIR sequence and presence of infarct on MRI-DWI) if > 6 hours or unknown last known well time;
3. Occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery confirmed by CTA/MRA/DSA;
4. Baseline ASPECTS score of 0-2 or infarct core volume ≥100ml;
5. The patient or patient's representative signs a written informed consent form.

Exclusion Criteria:

1. CT or MR evidence of hemorrhage;
2. Evidence of mass effect with ventricular effacement, midline shift or herniation on baseline imaging;
3. Vessel tortuosity where it is expected that the thrombectomy device will not be able to reach the occlusion site or result in unstable access;
4. History of bleeding disorders, severe heart, liver or kidney disease, or sepsis;
5. Currently participating in another investigational drug study;
6. Any terminal illness with life expectancy less than 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endovascular thrombectomy; Patients in this group will be treated with medical management plus endovascular thrombectomy	Drug: Medical management; Medical management includes IV thrombolysis, antiplatelet, and/or anticoagulation.; Procedure: Endovascular thrombectomy; Endovascular thrombectomy with stent-retriever, local aspiration, angioplasty, and/or stenting.
Active Comparator: Medical management; Patients in this group will be treated with medical management alone	Drug: Medical management; Medical management includes IV thrombolysis, antiplatelet, and/or anticoagulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale score	Modified Rankin scale score (mRS): scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful reperfusion	Final reperfusion grade of 2b-3 on eTICI scale (This 7-point compilation of TICI grades, termed the expanded TICI (eTICI), reflects all previously reported thresholds used to define reperfusion after endovascular stroke therapy. 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.)	Within 5 minutes at the end of angiogram
Rate of excellent outcome	Score of 0-1 on the modified Rankin scale	90 days after randomization
Rate of functional independence	Score of 0-2 on the modified Rankin scale	90 days after randomization
Rate of independent ambulation	Score of 0-3 on the modified Rankin scale	90 days after randomization

Collaborators and Investigators

• Sponsor: Zhongming Qiu
• Collaborators: Taizhou First People's Hospital; Xiangtan Central Hospital; Zhangzhou Affiliated Hospital of Fujian Medical University; Longyan First Affiliated Hospital of Fujian Medical University; The First Affiliated Hospital, University of South China; Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University
• Investigators: Principal Investigator: Guangxiong Yuan, Xiangtan Central Hospital; Principal Investigator: Congguo Yin, Hangzhou First Hospital of Zhejiang University; Principal Investigator: Tingyu Yi, Zhangzhou Affiliated Hospital of Fujian Medical University; Principal Investigator: Chong Zheng, Longyan First Hospital of Fujian Medical University; Principal Investigator: Chenghua Xu, Taizhou First People's Hospital; Principal Investigator: Zhongfan Ruan, The First Affiliated Hospital, Hengyang Medical School, University of South China

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: April 21, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Professional Practice; Organization and Administration; Health Services Administration; Practice Management; Practice Management, Medical
• Other Study ID Numbers: XL STROKE-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Two years after the trial results are revealed.
• IPD Sharing Access Criteria: After approval of a proposal from principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No