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

NCT07552610 | Not Yet Recruiting DMC

• 1 other identifier: IAT-TOP II
• Study Type: interventional
• Target: 868
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Ischemic Stroke; Large Vessel Occlusion; Thrombectomy; Neutrophil Extracellular Trap Formation

Keywords

Endovascular Thrombectomy; Sivelestat Sodium; Neutrophil elastase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

Study Arms (2)

Sivelestat Sodium + Endovascular Thrombectomy

EXPERIMENTAL

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; Procedure: Endovascular Thrombectomy

Placebo + Endovascular Thrombectomy

PLACEBO COMPARATOR

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.

Drug: Placebo; Procedure: Endovascular Thrombectomy

Interventions

Sivelestat sodium DRUG

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.

Sivelestat Sodium + Endovascular Thrombectomy

Placebo DRUG

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.

Placebo + Endovascular Thrombectomy

Endovascular Thrombectomy PROCEDURE

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 + Endovascular Thrombectomy; Sivelestat Sodium + Endovascular Thrombectomy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptoms and signs consistent with focal ischemia in the anterior circulation;
• Large vessel occlusion of the anterior circulation (internal carotid artery, M1/M2 segment of the middle cerebral artery) confirmed by CTA/MRA/DSA;
• Undergoing mechanical thrombectomy;
• Age between 18-80 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;
• Written informed consent provided by the patient or their legal representative.

You may not qualify if:

• ．Simultaneous acute occlusion of both the anterior and posterior circulation, or bilateral acute large-vessel occlusion in the anterior circulation;
• ．Failure to obtain a baseline NIHSS score before sedation or intubation by a neurologist or emergency physician;
• ．Seizure at stroke onset that precludes assessment of the baseline NIHSS score;
• ．Bilateral dilated pupils;
• ．Known allergy to sivelestat sodium or any of its excipients;
• ．Severe allergy or absolute contraindication to iodinated contrast agents;
• ．Systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg that cannot be controlled with antihypertensive therapy;
• ．Blood glucose \<50 mg/dL (2.8 mmol/L) or \>400 mg/dL (22.2 mmol/L);
• ．Platelet count \<50 \* 10⁹/L;
• ．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;
• ．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;
• ．Inability to complete the 90-day follow-up (e.g., no fixed residence or overseas patients);
• ．Suspected vasculitis or septic embolism;
• ．Suspected aortic dissection;
• ．Evidence of intracranial tumor (except small meningioma), acute intracranial hemorrhage, tumor, or arteriovenous malformation;

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (1)

Xuanwu Hospital, Capital Medical University.

Beijing, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: April 27, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)