Efficacy and Safety of Sodium Sivelestat as an Adjunct to Mechanical Thrombectomy in Acute Large Vessel Occlusion Stroke: A Prospective Single-Arm Exploratory Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Proportional distribution of modified Rankin Score
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 the standard treatment for large vessel occlusion (LVO) stroke; however, the phenomenon of "futile recanalization" remains common, with nearly half of patients failing to achieve favorable outcomes despite successful vessel reperfusion. Increasing evidence indicates that neutrophils and neutrophil extracellular traps (NETs) play pivotal roles in post-reperfusion inflammation, thrombosis, and microcirculatory dysfunction, contributing to thrombolysis resistance and poor prognosis. Neutrophil elastase (NE), a key component of NETs, exacerbates vascular injury and thrombus formation. Sodium sivelestat, a selective NE inhibitor, has demonstrated significant anti-inflammatory and organ-protective effects in patients with acute respiratory distress syndrome and in experimental models of cerebral ischemia. It can preserve blood-brain barrier integrity, attenuate brain edema, and improve neurological outcomes. Based on these findings, we propose a prospective, single-center, single-arm exploratory clinical trial to evaluate the efficacy and safety of sodium sivelestat as an adjunct to EVT in patients with acute LVO stroke within 24 hours of onset. The results of this study are expected to provide new clinical evidence for anti-inflammatory interventions aimed at reducing futile recanalization and improving functional outcomes in AIS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptoms and signs consistent with focal ischemia in the anterior or posterior circulation;
- •Large vessel occlusion of the anterior or posterior circulation (internal carotid artery, M1/M2 segment of the middle cerebral artery, vertebral artery, or basilar artery) confirmed by CTA/MRA/DSA;
- •Undergoing mechanical thrombectomy;
- •Age ≥18 years, both male and female;
- •Pre-stroke modified Rankin Scale (mRS) score ≤1;
- •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);
- •National Institutes of Health Stroke Scale (NIHSS) score ≥6 at admission;
- •ASPECTS ≥3 for anterior circulation occlusion, or pc-ASPECTS ≥6 for posterior circulation occlusion;
- •Written informed consent provided by the patient or their legal representative.
排除标准
- •Simultaneous acute occlusion of both anterior and posterior circulation or bilateral hemispheric large vessel occlusions;
- •Complete clinical recovery at the end of EVT procedure;
- •Arterial dissection or intraoperative hemorrhage indicated by post-thrombectomy DSA;
- •Sedated and intubated patients without baseline NIHSS assessment;
- •Seizure at stroke onset interfering with baseline NIHSS assessment;
- •Bilateral fixed dilated pupils;
- •Severe allergy or absolute contraindication to sodium sivelestat;
- •Severe allergy or absolute contraindication to iodinated contrast agents;
- •Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, uncontrolled despite antihypertensive therapy;
- •Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L);
- •Platelet count <50×10⁹/L;
- •Congenital or acquired bleeding diathesis, coagulation factor deficiency, or current use of oral anticoagulants with INR >1.7;
- •Severe renal impairment, defined as serum creatinine >3.0 mg/dl (265.2 μmol/L), GFR <30 ml/min, or requirement for hemodialysis/peritoneal dialysis;
- •Inability to complete 90-day follow-up (e.g., no fixed residence, overseas patient);
- •Suspected vasculitis or septic embolism;
- •Suspected aortic dissection;
- •Pre-existing neurological or psychiatric disorders interfering with stroke assessment;
- •Pregnancy or lactation;
- •Confirmed rheumatic/autoimmune disease with long-term use of immunosuppressants or corticosteroids;
- •Current treatment with chemotherapy or other immunomodulatory agents (e.g., recombinant human granulocyte colony-stimulating factor, Xuebijing, ulinastatin, etc.);
- •Participation in another clinical trial that may interfere with study outcomes;
- •Any other condition that investigators deem unsuitable for participation or that may pose significant risk to the patient.
研究组 & 干预措施
Intravenous Sodium Sivelestat Group
For enrolled patients, administer intravenous sodium sivelestat as soon as possible (recommended within 2 hours). The daily dosage is 4.8 mg/kg, delivered via continuous infusion with a microinfusion pump or intravenous drip, for a total duration of 5 days.
干预措施: Sodium Sivelestat (Drug)
结局指标
主要结局
Proportional distribution of modified Rankin Score
时间窗: 90 days (±7 days) after randomization
The mRS score range from 0 (no disability) to 6 (death)
次要结局
- Barthel Index(90 days (±7 days) after randomization)
- Rate of symptomatic intracranial hemorrhage (sICH)(Within 48 hours after randomization)
- Rate of mRS score of 0-3(90 days (±7 days) after randomization)
- Rate of modified Rankin Scale (mRS) score of 0-1(90 days (±7 days) after randomization)
- Rate of intracranial hemorrhage (ICH)(Within 48 hours after randomization)
- Rate of mRS score of 0-2(90 days (±7 days) after randomization)
- EQ-5D-5L(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)
- All-cause mortality(90 days (±7 days) after randomization)