Sivelestat Sodium as an Adjunct to Endovascular Thrombectomy for Acute Anterior Circulation Large-Vessel Occlusion

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

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.