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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke; Large Vessel Occlusion; Thrombectomy; Neutrophil Extracellular Trap Formation
• Intervention / Treatment: Drug: Sivelestat sodium; Procedure: Endovascular Thrombectomy; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 868
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Xuanwu Hospital, Capital Medical University.
    • Contact: Liqun Jiao, Dr.; Phone Number: +86 13911224991; Email: liqunjiao@sina.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Sivelestat sodium; Sivelestat sodium is a selective neutrophil elastase inhibitor administered as an adjunctive treatment to endovascular thrombectomy in this study. Treatment will be initiated within 2 hours after randomization and continued once daily until Day 7 after randomization or hospital discharge, whichever occurs first. The daily dose is 4.8 mg/kg, administered by continuous intravenous infusion using a microinfusion pump or by intravenous drip.; Procedure: Endovascular Thrombectomy; Endovascular thrombectomy will be performed according to standard clinical practice using NMPA-approved thrombectomy devices. First-line techniques may include aspiration thrombectomy, stent retriever thrombectomy, or a combined approach, with rescue procedures permitted when necessary at the investigator's discretion.
Placebo Comparator: 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.	Procedure: Endovascular Thrombectomy; Endovascular thrombectomy will be performed according to standard clinical practice using NMPA-approved thrombectomy devices. First-line techniques may include aspiration thrombectomy, stent retriever thrombectomy, or a combined approach, with rescue procedures permitted when necessary at the investigator's discretion.; Drug: Placebo; The placebo does not contain sivelestat sodium and consists of the same excipients as the investigational product without the active ingredient. It will be administered in the same manner, timing, and schedule as sivelestat sodium, beginning within 2 hours after randomization and continuing once daily until Day 7 after randomization or hospital discharge, whichever occurs first, in order to maintain blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of modified Rankin Scale (mRS) score of 0-2	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of mRS score of 0-3	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization
Proportional distribution of modified Rankin Score	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization
Improvement of the National Institutes of Health Stroke Scale (NIHSS) score	The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)	48 hours (±12 hours) after randomization
Improvement of the NIHSS score	The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)	7 days (±1 days) after randomization or discharge
EQ-5D-5L	The EQ-5D 5-Levels (EQ-5D-5L) range from 5 (no problems) to 25 (extreme problems), which deceased patients have a utility of 0.	90 days (±7 days) after randomization
Barthel Index	The Barthel Index range from 0 (severe disability) to 100 (no disability)	90 days (±7 days) after randomization
Rate of symptomatic intracranial hemorrhage (sICH)	The sICH was assessed based on the Heidelberg Bleeding Classification, defined as 1) ≥4 points total NIHSS at the time of diagnosis compared to immediately before worsening; 2) ≥2 point in one NIHSS category. The rationale for this is to capture new hemorrhages that produce new neurological symptoms, making them clearly symptomatic but not causing worsening in the original stroke territory; 3) Leading to intubation/hemicraniectomy/EVD placement or other major medical/surgical intervention; 4) Absence of alternative explanation for deterioration.	Within 48 hours after randomization
Rate of modified Rankin Scale (mRS) score of 0-1	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization
Rate of intracranial hemorrhage (ICH)	Any intracranial hemorrhage confirmed by imaging	Within 48 hours after randomization
Rate of early neurological improvement	Early neurological improvement, defined as an NIHSS score of 0-1 at 48 hours or a reduction of ≥4 points from baseline.	48 hours (±12 hours) after randomization
All-cause mortality	Death is defined as a mRS score of 6	90 days (±7 days) after randomization

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Endovascular Thrombectomy; Sivelestat Sodium; Neutrophil elastase
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: IAT-TOP II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No