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.
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;
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;
Parallel
Sivelestat sodium
DrugSivelestat 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.
Placebo
DrugThe 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.
Endovascular Thrombectomy
Procedure/SurgeryEndovascular 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.
Rate of modified Rankin Scale (mRS) score of 0-2
The mRS score range from 0 (no disability) to 6 (death)
Rate of modified Rankin Scale (mRS) score of 0-1
The mRS score range from 0 (no disability) to 6 (death)
Rate of mRS score of 0-3
The mRS score range from 0 (no disability) to 6 (death)
Proportional distribution of modified Rankin Score
The mRS score range from 0 (no disability) to 6 (death)
Improvement of the National Institutes of Health Stroke Scale (NIHSS) score
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
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