Cerebrolysin After Reperfusion in Extended-Window Endovascular Thrombectomy: A Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 主要终点
- Final Infarct Volume on Diffusion-Weighted MRI
研究概览
简要总结
Acute ischemic stroke caused by blockage of a large brain artery can lead to severe disability. Endovascular thrombectomy is a catheter-based procedure used to remove the blood clot and restore blood flow. It can benefit selected patients treated 6 to 24 hours after stroke onset, but some patients remain disabled even when the blocked artery is successfully reopened. Ongoing injury to brain tissue, small blood vessels, and the blood-brain barrier may contribute to this incomplete recovery.
This multicenter randomized clinical trial will evaluate whether Cerebrolysin, given after successful extended-window endovascular thrombectomy, can reduce brain tissue injury and support recovery. The study will enroll 100 adults aged 18 to 80 years at three stroke centers in Taiwan. Participants will be randomly assigned, after successful reperfusion has been confirmed, to receive either Cerebrolysin 30 mL or a matched normal saline placebo by intravenous infusion once daily for 10 consecutive days. The first infusion will begin within 36 hours of stroke onset. All participants will also receive standard stroke care and rehabilitation.
The primary outcome is final infarct volume measured by diffusion-weighted magnetic resonance imaging on Day 7 to Day 10. Other outcomes include functional recovery at 3 and 12 months, neurological improvement, symptomatic intracranial hemorrhage, cerebral edema, recurrent stroke, mortality, cognition, language, and mood. The study will also examine blood-brain barrier injury using computed tomography perfusion, dynamic contrast-enhanced magnetic resonance imaging, and serial plasma Claudin-5 measurements.
This study will determine whether Cerebrolysin shows evidence of reducing postreperfusion brain injury after successful thrombectomy and will help guide the design of a larger trial focused on clinical outcomes.
详细描述
This is an investigator-initiated, multicenter, randomized, placebo-controlled, participant- and outcome-assessor-blinded proof-of-concept trial conducted at three stroke centers within the Chang Gung Memorial Hospital system in Taiwan.
The study will enroll 100 participants aged 18 to 80 years with anterior-circulation acute ischemic stroke caused by internal carotid artery or M1/M2 middle cerebral artery occlusion. Eligible participants must undergo endovascular thrombectomy more than 6 hours and no more than 24 hours after stroke onset and must achieve successful reperfusion, defined as modified Thrombolysis in Cerebral Infarction grade 2b or 3, before randomization.
Participants will be randomized in a 1:1 ratio to receive Cerebrolysin 30 mL diluted in 70 mL normal saline or matched normal saline placebo. Study treatment will be administered intravenously over 60 minutes once daily for 10 consecutive days and will begin after randomization and within 36 hours of stroke onset. Both groups will receive standard post-thrombectomy stroke care, secondary prevention, and rehabilitation.
The primary outcome is final infarct volume measured on diffusion-weighted magnetic resonance imaging performed on Day 7 to Day 10. The key secondary clinical outcome is functional independence, defined as a modified Rankin Scale score of 0 to 2, at Month 3. Other outcomes include ordinal modified Rankin Scale, National Institutes of Health Stroke Scale, Barthel Index, symptomatic intracranial hemorrhage, asymptomatic hemorrhagic transformation, cerebral edema, recurrent stroke, all-cause mortality, vessel patency, cognition, language, and mood through Month 12.
Mechanistic assessments will evaluate blood-brain barrier injury. Computed tomography perfusion-derived blood-brain barrier permeability will be measured before thrombectomy and approximately 24 hours after reperfusion. Dynamic contrast-enhanced magnetic resonance imaging will assess subacute permeability on Day 7 to Day 10. Plasma Claudin-5, an exploratory marker of endothelial tight-junction injury, will be measured at groin puncture before reperfusion, 24 hours after reperfusion, and on Day 7.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Participants, treating clinicians and bedside staff not involved in study-drug preparation, investigators, outcome assessors, imaging readers, and statisticians will remain blinded to treatment allocation. Designated unblinded pharmacy or nursing personnel will prepare and administer the study infusion. Infusion bags, drip chambers, and visible tubing will be covered with opaque material. Emergency unblinding will be permitted only when knowledge of treatment allocation is essential for immediate clinical management.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 80 years.
- •Acute anterior-circulation ischemic stroke caused by internal carotid artery or M1 or M2 middle cerebral artery occlusion confirmed by computed tomography angiography.
- •Stroke onset-to-groin-puncture interval greater than 6 hours and no more than 24 hours.
- •Prestroke modified Rankin Scale score of 0 to
- •Baseline National Institutes of Health Stroke Scale score of at least 6 with cortical signs.
- •Alberta Stroke Program Early Computed Tomography Score greater than
- •Computed tomography perfusion target mismatch defined as ischemic core volume less than 70 mL, mismatch ratio at least 1.8, and mismatch volume at least 15 mL.
- •Moderate-to-good collateral circulation, defined as filling of more than 50% of the middle cerebral artery territory on computed tomography angiography.
- •Successful endovascular reperfusion, defined as modified Thrombolysis in Cerebral Infarction grade 2b or 3, confirmed before randomization.
- •Study treatment can be initiated within 36 hours of stroke onset.
- •Written informed consent obtained before randomization from the participant or a legally authorized representative.
排除标准
- •Life expectancy less than 6 months or a serious medical, neurological, or psychiatric condition likely to interfere with study treatment, follow-up, or outcome assessment.
- •Current pregnancy or breastfeeding.
- •Known iodinated contrast allergy that precludes required endovascular or imaging procedures.
- •Acute or chronic renal failure with creatinine clearance less than 30 mL/min.
- •Known hypersensitivity or contraindication to Cerebrolysin.
- •Aspartate aminotransferase or alanine aminotransferase greater than 2 times the upper limit of normal, or total bilirubin greater than 2 mg/dL.
- •Blood glucose less than 50 mg/dL or greater than 400 mg/dL.
- •Platelet count less than 50,000/mm3 or international normalized ratio greater than
- •Seizure at stroke onset that prevents reliable neurological assessment.
- •Pre-existing intracranial hemorrhage or multiple vascular occlusions on baseline neuroimaging.
研究组 & 干预措施
Cerebrolysin After Successful Extended-Window Thrombectomy
Participants will receive Cerebrolysin 30 mL diluted in 70 mL normal saline, administered intravenously over 60 minutes once daily for 10 consecutive days. The first infusion will begin after successful endovascular reperfusion and randomization and within 36 hours of stroke onset. All participants will also receive standard post-thrombectomy stroke care, secondary prevention, and rehabilitation.
干预措施: Cerebrolysin (Drug)
Matched Placebo After Successful Extended-Window Thrombectomy
Participants will receive 100 mL normal saline placebo, administered intravenously over 60 minutes once daily for 10 consecutive days according to the same schedule as the experimental arm. The first infusion will begin after successful endovascular reperfusion and randomization and within 36 hours of stroke onset. All participants will also receive standard post-thrombectomy stroke care, secondary prevention, and rehabilitation.
干预措施: Normal saline placebo (Drug)
结局指标
主要结局
Final Infarct Volume on Diffusion-Weighted MRI
时间窗: Day 7 to Day 10 after stroke onset
Final infarct volume will be quantified on Day 7-10 diffusion-weighted magnetic resonance imaging using standardized semiautomated lesion segmentation with manual correction when required. Imaging readers will be blinded to treatment allocation. Participants who are unable to undergo MRI will remain in the intention-to-treat population, and missing primary-outcome data will be addressed using prespecified imputation and sensitivity analyses.
次要结局
- Montreal Cognitive Assessment Score(Months 3, 6, and 12)
- Functional Independence Defined as Modified Rankin Scale Score 0-2(Month 3 and Month 12 after stroke onset)
- Symptomatic Intracranial Hemorrhage(Within 7 days after stroke onset)
- Change in Computed Tomography Perfusion-Derived Blood-Brain Barrier Permeability(Pre-EVT and 24 ± 6 hours after reperfusion)
- Plasma Claudin-5 Concentration-Time Profile(At groin puncture before reperfusion, 24 ± 6 hours after reperfusion, and Day 7 ± 1)
- Recurrent Stroke(Through Month 12)