A Randomized, Open-label, Blinded Endpoint Evaluation Study of Early Administration of Evolocumab After Thrombolysis in Patients With Atherosclerotic Acute Ischemic Stroke
概览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 132
- 试验地点
- 1
- 主要终点
- Early deterioration of neurological function (END)
概览
简要总结
This study is a Phase IIa clinical trial initiated by the researchers, which is prospective, single-center, randomized, open-label, with blinded endpoint evaluation (PROBE design). Patients were screened through the emergency stroke green channel and included if they had an onset within 9 hours, met the criteria for large artery atherosclerosis (LAA) after multimodal imaging screening, received intravenous thrombolysis, and signed informed consent to participate. The study used block randomization (block size of 4), stratified by baseline National Institutes of Health Stroke Scale (NIHSS) score (5-10 vs >10-20) and onset-to-thrombolysis time (<4.5 hours vs 4.5-9 hours).
Intervention group: received subcutaneous injections of Ilyumumab 420 mg (three syringes) within 24 hours after thrombolysis plus standard drug therapy (including statins). Control group: received conventional statin therapy (atorvastatin 20 mg/day) after thrombolysis. All patients received standardized stroke treatment (initiating antiplatelet therapy 24 hours after thrombolysis) and standardized management of blood pressure and blood glucose.
NIHSS scores were assessed every 12 hours within 72 hours post-thrombolysis, and then daily thereafter, to evaluate the effectiveness of combined therapy in reducing early neurological deterioration (END).
Blinding: The study is open-label. An independent Clinical Endpoint Committee (CEC) was established, and all clinical endpoint events (END assessment, 90-day mRS scores) were evaluated in a blinded manner by experts who were completely unaware of group assignments.
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
- •1\. Age 18-85 years. No gender or sex restrictions, and no gender ratio restrictions.
- •2\. Clinically diagnosed with acute ischemic stroke, with the time from symptom onset to intravenous thrombolysis \<9 hours.
- •Within 4.5 hours of symptom onset: This time window is based on the ECASS III criteria (Class IA recommendation) and is currently the standard indication for intravenous thrombolysis in acute ischemic stroke worldwide.
- •4.5-9 hours: Referring to the EXTEND study criteria, meeting the following multimodal imaging mismatch ratio: ischemic penumbra volume/ischemic core volume \>1.2, with an absolute mismatch volume \>10 mL and an ischemic core volume \<70 mL.
- •3\. The stroke meets the TOAST classification for large artery atherosclerosis (LAA), which includes intracranial arteriosclerosis (ICAS) and extracranial arteriosclerosis (ECAS), and meets one of the following three criteria: large artery stenosis ≥50%, infarct lesion \>1.5cm + ipsilateral plaque (no stenosis requirement), or intracranial artery stenosis ≥30% with plaque ulceration.
- •4\. The patient or their legal representative has signed an informed consent form.
排除标准
- •1\. CT scan showing signs of intracranial hemorrhage, symptomatic intracranial hemorrhage, or subarachnoid hemorrhage, even if the CT scan results are normal.
- •2\. Patients who must or wish to continue using restrictive medications or any medications that may interfere with the safe conduct of the trial.
- •3\. Acute bleeding tendency, including but not limited to:
- •A known family history of bleeding disorders and a history of a serious bleeding disorder currently present or within the past 6 months.
- •Receiving heparin treatment within the past 48 hours, with an activated partial thromboplastin time (aPTT) exceeding the upper limit of the normal range for laboratory testing.
- •Currently taking an oral vitamin K anticoagulant (e.g., warfarin) with a prolonged prothrombin time (INR \> 1.7 or PT \> 15 seconds); or currently taking a novel oral anticoagulant (e.g., dabigatran etexilate, rivaroxaban, or apixaban) with an activated partial thromboplastin time (aPTT) and/or prothrombin time (PT) exceeding the upper limit of the local laboratory reference range.
- •Platelet count below 100,000/mm³ at screening.
- •History of central nervous system injury (e.g., tumor, aneurysm, intracranial or spinal surgery).
- •Experiencing traumatic external cardiac compression, obstetric delivery, or non-compressive vascular puncture (e.g., subclavian or jugular vein puncture) within the past 10 days.
- •Known history of suspected intracranial hemorrhage or suspected aneurysm/subarachnoid hemorrhage.
研究组 & 干预措施
evolocumab
Within 24 hours after thrombolysis, patients received subcutaneous injections of 420 mg evokine and three vials of evokine, along with standard statin therapy (atorvastatin 20 mg/day).
干预措施: Ivolumab 420mg (three vials) (Drug)
结局指标
主要结局
Early deterioration of neurological function (END)
时间窗: within 1-7 days after thrombolysis.
Defined as an increase of ≥2 points in NIHSS score or death within 1-7 days after thrombolysis. NIHSS scores should be assessed daily.The NIHSS (National Institutes of Health Stroke Scale) has a total score of 0 to 42. The higher the total score, the more severe the neurological deficit caused by stroke.
次要结局
- Therapeutic efficacy(Within 90 days after thrombolysis)
- Mechanism exploration(from baseline to 36 hours and 72 hours after thrombolysis.)
- Mechanism Exploration(from baseline to 36 hours and 72 hours after thrombolysis)
- Preset subgroup analysis(within 1-7 days after thrombolysis)