Efficacy and Safety of Sivelestat Sodium as an Adjunct to Endovascular Thrombectomy in Acute Anterior Circulation Large-Vessel Occlusion: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 868
- 试验地点
- 2
- 主要终点
- Rate of modified Rankin Scale (mRS) score of 0-2
研究概览
简要总结
Stroke remains a major global health burden, with acute ischemic stroke (AIS) accounting for more than 65% of all cases. Endovascular thrombectomy (EVT) has been established as a standard treatment for large vessel occlusion (LVO) stroke; however, "futile recanalization" remains common, with many patients failing to achieve favorable functional outcomes despite successful vessel reperfusion. Increasing evidence indicates that neutrophils and neutrophil extracellular traps (NETs) play important roles in post-reperfusion inflammation, thrombosis, and microcirculatory dysfunction, which may contribute to thrombolysis resistance and poor prognosis. Neutrophil elastase (NE), a key component associated with NETs, may further aggravate vascular injury and thrombus formation.
Sivelestat Sodium is a selective NE inhibitor that has demonstrated anti-inflammatory and organ-protective effects in patients with acute respiratory distress syndrome and in experimental models of cerebral ischemia. It may help preserve blood-brain barrier integrity, reduce brain edema, and improve neurological outcomes. Based on these findings, this study is designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of sivelestat sodium as an adjunct to EVT in patients with acute anterior circulation large-vessel occlusive stroke within 24 hours of onset. The results of this study are expected to provide further clinical evidence for anti-inflammatory adjunctive treatment strategies aimed at reducing futile recanalization and improving functional outcomes in AIS.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This trial will be conducted using a double-blind design, in which neither the investigators nor the participants will be aware of the assigned intervention. In addition, outcome assessors will evaluate the study endpoints objectively while remaining blinded to treatment allocation.
Participants in the investigational group and the control group will be assigned in a 1:1 ratio. The sivelestat sodium injection and placebo will be identically packaged. The investigational product and placebo will be indistinguishable in physicochemical properties, appearance, packaging, and labeling, and will differ only by drug number. The drug number will be affixed directly to the outer package. The randomization code will be kept by an unblinded statistician and must not be disclosed.
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
- •1.Symptoms and signs consistent with focal ischemia in the anterior circulation;
- •2.Large vessel occlusion of the anterior circulation (internal carotid artery, M1/M2 segment of the middle cerebral artery) confirmed by CTA/MRA/DSA;
- •3.Undergoing mechanical thrombectomy;
- •4.Age between 18-80 years, both male and female;
- •5.Pre-stroke modified Rankin Scale (mRS) score ≤1;
- •6.Time from symptom onset to thrombectomy ≤24 hours, including wake-up stroke or unwitnessed stroke; symptom onset is defined as the "last known well" (LKW);
- •7.National Institutes of Health Stroke Scale (NIHSS) score ≥6 at admission;
- •8.ASPECTS ≥3 for anterior circulation occlusion;
- •9.Written informed consent provided by the patient or their legal representative.
排除标准
- •1．Simultaneous acute occlusion of both the anterior and posterior circulation, or bilateral acute large-vessel occlusion in the anterior circulation;
- •2．Failure to obtain a baseline NIHSS score before sedation or intubation by a neurologist or emergency physician;
- •3．Seizure at stroke onset that precludes assessment of the baseline NIHSS score;
- •4．Bilateral dilated pupils;
- •5．Known allergy to sivelestat sodium or any of its excipients;
- •6．Severe allergy or absolute contraindication to iodinated contrast agents;
- •7．Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg that cannot be controlled with antihypertensive therapy;
- •8．Blood glucose <50 mg/dL (2.8 mmol/L) or >400 mg/dL (22.2 mmol/L);
- •9．Platelet count <50 * 10⁹/L;
- •10．Hereditary or acquired bleeding tendency, coagulation factor deficiency, current oral anticoagulant use with INR >1.7, or oral anticoagulant treatment within the previous 48 hours;
- •11．Severe renal failure, defined as serum creatinine >3.0 mg/dL (265.2 μmol/L), glomerular filtration rate (GFR) <30 mL/min, or requirement for hemodialysis or peritoneal dialysis;
- •12．Inability to complete the 90-day follow-up (e.g., no fixed residence or overseas patients);
- •13．Suspected vasculitis or septic embolism;
- •14．Suspected aortic dissection;
- •15．Evidence of intracranial tumor (except small meningioma), acute intracranial hemorrhage, tumor, or arteriovenous malformation;
- •16．Significant mass effect with midline shift;
- •17．Evidence of internal carotid artery dissection causing flow limitation;
- •18．Neurological disease or psychiatric disorder that may interfere with evaluation of the patient's condition;
- •19．Pregnant or breastfeeding women;
- •20．Confirmed rheumatic or autoimmune disease with long-term use of immunosuppressants or corticosteroids;
- •21．Current treatment with chemotherapy or other immunomodulatory agents (e.g., recombinant human granulocyte colony-stimulating factor, Xuebijing, or ulinastatin);
- •22．Participation in another clinical trial that may interfere with the results of this study;
- •23．Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation or may pose a significant risk to the patient.
研究组 & 干预措施
Placebo + Endovascular Thrombectomy
Participants randomized to the control arm will receive placebo in addition to standard EVT. The placebo does not contain sivelestat sodium and will be administered in the same manner as the investigational product, beginning within 2 hours after randomization and continuing once daily until Day 7 after randomization or hospital discharge, whichever occurs first. The placebo is matched to sivelestat sodium in appearance, packaging, labeling, and method of administration to maintain blinding. EVT will be performed according to standard clinical practice.
干预措施: Endovascular Thrombectomy (Procedure)
Sivelestat Sodium + Endovascular Thrombectomy
Participants randomized to the experimental arm will receive sivelestat sodium injection in addition to standard endovascular thrombectomy (EVT). Sivelestat sodium will be initiated within 2 hours after randomization and administered once daily until Day 7 after randomization or hospital discharge, whichever occurs first. The daily dose is 4.8 mg/kg, given by continuous infusion using a microinfusion pump or by intravenous drip. EVT will be performed according to standard clinical practice using NMPA-approved thrombectomy devices.
干预措施: Endovascular Thrombectomy (Procedure)
Placebo + Endovascular Thrombectomy
Participants randomized to the control arm will receive placebo in addition to standard EVT. The placebo does not contain sivelestat sodium and will be administered in the same manner as the investigational product, beginning within 2 hours after randomization and continuing once daily until Day 7 after randomization or hospital discharge, whichever occurs first. The placebo is matched to sivelestat sodium in appearance, packaging, labeling, and method of administration to maintain blinding. EVT will be performed according to standard clinical practice.
干预措施: Placebo (Drug)
Sivelestat Sodium + Endovascular Thrombectomy
Participants randomized to the experimental arm will receive sivelestat sodium injection in addition to standard endovascular thrombectomy (EVT). Sivelestat sodium will be initiated within 2 hours after randomization and administered once daily until Day 7 after randomization or hospital discharge, whichever occurs first. The daily dose is 4.8 mg/kg, given by continuous infusion using a microinfusion pump or by intravenous drip. EVT will be performed according to standard clinical practice using NMPA-approved thrombectomy devices.
干预措施: Sivelestat sodium (Drug)
结局指标
主要结局
Rate of modified Rankin Scale (mRS) score of 0-2
时间窗: 90 days (±7 days) after randomization
The mRS score range from 0 (no disability) to 6 (death)
次要结局
- Rate of modified Rankin Scale (mRS) score of 0-1(90 days (±7 days) after randomization)
- Rate of mRS score of 0-3(90 days (±7 days) after randomization)
- Proportional distribution of modified Rankin Score(90 days (±7 days) after randomization)
- Improvement of the National Institutes of Health Stroke Scale (NIHSS) score(48 hours (±12 hours) after randomization)
- Rate of early neurological improvement(48 hours (±12 hours) after randomization)
- Improvement of the NIHSS score(7 days (±1 days) after randomization or discharge)
- EQ-5D-5L(90 days (±7 days) after randomization)
- Barthel Index(90 days (±7 days) after randomization)
- Rate of intracranial hemorrhage (ICH)(Within 48 hours after randomization)
- Rate of symptomatic intracranial hemorrhage (sICH)(Within 48 hours after randomization)
- All-cause mortality(90 days (±7 days) after randomization)