Rapid Local Ischemic Postconditioning Following Successful Recanalization After Endovascular Thrombectomy in Large Ischemic Core Stroke
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 448
- 主要终点
- Phase IIb: proportion of subjects with midline shift ( >3mm)
研究概览
简要总结
The main goal of this study is to find out if a new, quick "brain rescue" procedure can help people recover better from a severe stroke caused by a large vessel occlusion.
When someone has this type of stroke, doctors often perform a procedure called an endovascular thrombectomy (EVT). In EVT, they thread a thin tube through a blood vessel up to the brain to remove the clot and restore blood flow. This is a highly effective treatment.
However, for some patients, suddenly restoring blood flow can cause additional, unexpected injury to the brain. This is called "reperfusion injury." This study tests a technique called rapid local ischemic postconditioning (RL-IPostC) that might prevent this extra damage. It's a very simple additional step performed immediately after the clot is successfully removed.
The doctor would briefly inflate and deflate a tiny balloon inside the proximal brain artery after recanalization, creating very short, controlled "pauses" in blood flow. This is believed to give brain cells a gentler "wake-up" call, helping them tolerate the return of oxygen-rich blood.
The study will test two different "doses" of this procedure (meaning different numbers of inflation/deflation cycles) against the standard care (no additional procedure).
Phase IIb (the first part): Which dose of RL-IPostC (high or low) is more promising for reducing early brain swelling (measured by whether the brain's midline has shifted less than 3 mm on a 24-hour scan)? Phase III (the main part): Using the best dose from Phase IIb, does RL-IPostC improve a patient's functional recovery three months later, specifically enabling them to walk and manage daily activities without help? A total of 288 participants who have had a large-vessel occlusion stroke and successful clot removal will be enrolled. If early results look promising but not quite conclusive, the study can increase the total number of participants up to 448 to get a clearer answer.
If successful, this study could identify a simple, low-cost add-on procedure to a standard stroke treatment that improves long-term recovery and quality of life for thousands of stroke patients. It's a potential new tool to protect the brain after blood flow is restored. This is a carefully designed study testing a gentle "on/off" blood flow technique right after clot removal, to see if it can reduce brain injury and help people walk and live more independently after a severe stroke.
详细描述
RAPID IMPROVE is a seamless design which integrates dose selection (Phase IIb) and confirmatory testing (Phase III) into a single continuous trial. This approach preserves study power, controls the overall type I error rate, and accelerates the evaluation of rapid local ischemic postconditioning (RL-IPostC) in patients with acute anterior circulation large-core ischemic stroke who achieve successful recanalization defined as modified Thrombolysis In Cerebral Infarction (mTICI) 2b/3 after mechanical thrombectomy.
Randomization is performed centrally using a web-based system immediately after confirmation of successful recanalization. In Phase IIb, eligible patients are allocated 1:1:1 to high-dose RL-IPostC, low-dose RL-IPostC, or control (no postconditioning). After the dose selection decision at the end of Phase IIb, Phase III continues with a 1:1 randomization between the selected dose and control. Randomization is stratified by stroke onset to imaging time (<6 hours vs. 6-24 hours) and baseline NIHSS score (<17 vs. ≥17) to ensure balance of prognostic factors.
The treating interventionalist cannot be blinded due to the nature of the postconditioning procedure. However, all outcome assessors - including the investigators who perform follow-up mRS assessments, the imaging core laboratory personnel, and the clinical events committee - are blinded to treatment assignment. The Data Safety Monitoring Board (DSMB) has access to unblinded data for safety monitoring. An imaging core laboratory centrally evaluates all baseline and follow-up CT, CTA, CTP, MRI, and DSA images. Separate analysts interpret baseline eligibility images (ASPECTS, core volume) and post-procedure images (midline shift, infarct volume, net water uptake, CSF/ICV ratio), all blinded to treatment allocation.
RL-IPostC is performed using a balloon guide catheter (BGC) positioned at the C1-C2 segment of the ipsilateral internal carotid artery, carefully avoiding the carotid sinus. The intervention should be initiated as soon as possible after confirmation of successful recanalization, and no later than 5 minutes. All patients receive standard post-thrombectomy care in a stroke unit, including a mandatory repeat CT scan at 24 hours. Antithrombotic or antiplatelet therapy is given according to local clinical practice and is recorded.
The trial uses a 3-arm, 2-stage multi-arm multi-stage (MAMS) design. The primary endpoint for stage 1 (Phase IIb) is the absence of midline shift (>3 mm at the level of the septum pellucidum) on 24 hours imaging (non-contrast computed tomography or magnetic resonance imaging). Based on the research team's cohort study, the control arm response rate (absence of midline shift) is assumed to be 40%, with an absolute improvement of 30% for an effective dose. One-sided α = 0.10, power = 95%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-85 years
- •Diagnosis of acute ischemic stroke
- •Pre-stroke mRS 0-1
- •Baseline NIHSS score ≥ 6
- •Time from symptom onset to start of endovascular procedure (puncture) < 24 hours; onset time defined as "last known well" time
- •Imaging criteria: ASPECTS 3-5 on CT, or ASPECTS > 5 with acute ischemic core volume (defined as rCBF < 30% or ADC < 620) ≥ 50 mL
- •Occlusion of the intracranial segment of the internal carotid artery or the middle cerebral artery (M1/M2), confirmed as the symptomatic culprit vessel
- •After thrombectomy, the culprit vessel is considered to be occluded by an embolus, and successful recanalization (mTICI 2b/3, i.e., ≥ 50% perfusion) is achieved
- •Written informed consent signed by the patient or a legal representative
排除标准
- •Presence of stenosis (≥ 50%) in the ipsilateral middle cerebral artery, internal carotid artery, or common carotid artery proximal to the occlusion site
- •Multiple emboli across different circulations (simultaneous anterior and posterior circulation emboli, or simultaneous left and right anterior circulation emboli)
- •Evidence on CT of extensive cerebral edema, midline shift, significant mass effect, or signs of brain herniation
- •Presence of a life-threatening disease with a prognosis < 6 months, making 3-month follow-up impossible
- •Severe psychiatric disorder or heart failure
- •Concurrent participation in another clinical drug or device study
- •Any other condition that, in the investigator's judgment, makes the subject unsuitable for this study
研究组 & 干预措施
Low-dose RL-IPostC
Postconditioning intervention with 15 seconds of inflation / 15 seconds of deflation, for 5 cycles.
干预措施: Low-dose RL-IPostC (Procedure)
Control
No postconditioning intervention after successful thrombectomy.
High-dose RL-IPostC
Postconditioning intervention with 2 minutes of inflation / 2 minutes of deflation, for 4 cycles.
干预措施: High-dose RL-IPostC (Procedure)
结局指标
主要结局
Phase IIb: proportion of subjects with midline shift ( >3mm)
时间窗: 24 ± 6 hours after randomization
Midline shift was measured at the level of the translucent septum in the follow-up NCCT at 24 hours.
Phase III: Proportion of subjects with mRS 0-3 at 90 days.
时间窗: 90 ± 7 days post-procedure
The modified Rankin Scale (mRS) is a single-item, global outcome rating scale used to measure the degree of disability or dependence in the daily activities of people who have suffered a stroke or other neurological disorders. The mRS is a 7-level ordinal scale ranging from 0 to 6, where higher scores indicate greater disability. 0-No symptoms at all 1. No significant disability despite symptoms: able to carry out all usual duties and activities 2. Slight disability：unable to carry out all previous activities but able to look after own affairs without assistance 3. Moderate disability：require some help, but able to walk without assistance 4. Moderate severe disability：unable to walk without assistance, and unable to attend to own bodily needs without assistance 5. Severe disability：bedridden, incontinent, and require constant nursing care and attention 6. Death
次要结局
- Proportion of subjects with good outcome (mRS 0-2) at 90 days(90 ± 7 days post-procedure)
- Distribution of mRS at 90 days(90 ± 7 days post-procedure)
- Proportion of subjects with mRS 0-3 at 1 year(1 year ± 15 days post-procedure.)
- Proportion of subjects with mRS 0-2 at 1 year(1 year ± 15 days post-procedure.)
- Distribution of mRS at 1 year.(1 year ± 15 days post-procedure.)
- Change in NIHSS score between day 5-7 or discharge(Day 5-7 post-procedure.)
- EQ-5D-5L score at 90 days(90 ± 7 days post-procedure)
- EQ-5D-5L score at 1 year(1 year ± 15 days post-procedure.)
研究者
Yueqi Zhu
Head of Interventional Radiology Department
Shanghai Jiao Tong University Affiliated Sixth People's Hospital