Elaspol (sivelestat) / Ono Pharmaceutical - LARVOL DELTA

Sodium Sivelestat With Mechanical Thrombectomy for Acute Stroke: A Pilot Study (clinicaltrials.gov) - P=N/A | N=20 | Completed | Sponsor: Xuanwu Hospital, Beijing | Recruiting ➔ Completed

Trial completion • Cardiovascular • Ischemic stroke

EFFICACY AND SAFETY OF NEUTROPHIL ELASTASE INHIBITORS (SIVELESTAT AND ULINASTATIN) FOR POSTOPERATIVE LUNG INJURY AFTER AORTIC DISSECTION SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS (ACC 2026) - "Sivelestat and Ulinastatin do not reduce mortality but improve postoperative oxygenation and inflammation and may facilitate recovery. Larger high-quality trials are required to define itsclinical role."

Retrospective data • Review • Surgery • Inflammation • Respiratory Diseases • ELANE • IL6

Preventing ARDS, Not Treating It-Lessons From Sivelestat After Cardiopulmonary Bypass. (PubMed, JAMA Netw Open) - No abstract available

Journal • Acute Respiratory Distress Syndrome

Sivelestat and Incidence of Acute Respiratory Distress Syndrome After Cardiovascular Surgery: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P3 | "These preliminary findings suggest sivelestat may be a pharmacologic option to mitigate ARDS in cardiovascular procedures. ClinicalTrials.gov Identifier: NCT06276569."

Clinical • Journal • Acute Respiratory Distress Syndrome • Cardiovascular • Critical care • Infectious Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • ELANE • IL6 • TNFA

Neutrophil extracellular traps-inhibited nanoplatform achieves comprehensive treatment of rheumatoid arthritis at different stages. (PubMed, J Control Release) - "BTST was synthesized by conjugating bovine serum albumin (BSA) and sivelestat (ST) via ROS-sensitive thioketal bonds...In vivo biodistribution and pharmacological experiments illustrated that BTST NPs could be efficiently transported by activated neutrophils to inflamed joints and exhibit favorable therapeutic effects across different RA stages. The construction of BTST NPs provides a new strategy for functional integration in treating RA at various stages."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

PALETTE: Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial (clinicaltrials.gov) - P2 | N=2000 | Not yet recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Phase classification: P3 ➔ P2 | Trial completion date: Apr 2032 ➔ May 2031 | Trial primary completion date: May 2029 ➔ Jun 2028

Pan tumor • Phase classification • Trial completion date • Trial primary completion date • Infectious Disease • Septic Shock

Efficacy of sivelestat sodium for patients with acute lung injury and acute respiratory distress syndrome: a protocol for systematic review and meta-analysis. (PubMed, Syst Rev) - "This protocol outlines a systematic approach for evaluating sivelestat sodium's efficacy in ARDS/ALI through the integration of English and Japanese literature. Methodological rigor will ensure high-quality evidence synthesis despite challenges in integrating diverse studies. This research addresses a significant gap, as meta-analyses incorporating Japanese publications have been absent for over a decade. The findings will provide evidence-based guidance for clinical practice, inform individualized treatment strategies, optimize sivelestat administration protocols, and identify directions for future research."

Journal • Retrospective data • Acute Lung Injury • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases • ELANE

Mechanical ventilation strategies and lung protection during cardiopulmonary bypass: A scoping review. (PubMed, Perfusion) - "When combined with protective measures (low tidal volume [LTV], moderate positive end-expiratory pressure [PEEP], and recruitment maneuvers), they show clinical efficacy in lung protection. Pharmacologic agents like ambroxol, neutrophil elastase inhibitors, and sivelestat further enhance protection, underscoring the promise of combined mechanical-pharmacological strategies against CPB-induced lung injury.ConclusionsA comprehensive approach integrating individualized ventilation management and pharmacological intervention is key to reducing CPB-induced lung injury, enhancing postoperative respiratory function, and improving patient outcomes."

Journal • Review • Cardiovascular • Inflammation • Respiratory Diseases • ELANE

A dual pH/ROS-sensitive nanoplatform blocking NETs formation and co-delivering paclitaxel for potent therapeutic efficacy against triple-negative breast cancer and lung metastasis. (PubMed, Nanoscale) - "This nanoplatform enables controlled, microenvironment-responsive release of paclitaxel (PTX) and the neutrophil elastase inhibitor sivelestat (SIV) in acidic and oxidative tumor tissues. Furthermore, the nanoplatform displayed favorable systemic safety with negligible organ toxicity. This dual-responsive, NET-modulating nanoplatform provides a potent and safe therapeutic strategy for combating TNBC and preventing its metastasis, offering strong potential for clinical translation."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ELANE

MicroRNA-223/NE Signaling Pathway Inhibits Lipopolysaccharide-Induced Acute Lung Injury by Regulating Neutrophil Extracellular Traps. (PubMed, Mediators Inflamm) - "The roles of the miR-223/NE/NETs axis were further investigated using the NETs inhibitor GSK484 and the NE inhibitor Sivelestat. This study reveals that the miR-223/NE axis critically regulates NETs formation, modulating neutrophil inflammatory infiltration and neutrophil-epithelial interactions to exacerbate ALI. These findings provide potential therapeutic targets for ALI."

Journal • Acute Lung Injury • Inflammation • Respiratory Diseases • ELANE • IL1B • IL6 • MIR223 • MPO • TNFA

Sivelestat sodium mitigates lung injury post-acute pulmonary embolism by inhibiting NE-SPP1 neutrophil recruitment and restoring redox balance. (PubMed, Sci Rep) - "Sivelestat sodium alleviates APE by inhibiting the NE-SPP1 axis, thereby reducing inflammation, oxidative stress, fibrosis, and endothelial injury. This identifies SPP1 as a novel therapeutic target for APE treatment."

Journal • Cardiovascular • Fibrosis • Immunology • Inflammation • Pulmonary Embolism • Respiratory Diseases • CXCL8 • ELANE • GPX1 • GPX7 • GSTM2 • IL1B • IL6 • SPP1 • TNFA

Lack of S100A8 impairs lung protective immunity against Streptococcus pneumoniae. (PubMed, J Infect Dis) - "Deletion of S100A8 disturbs lung protective immunity against S. pneumoniae in mice. At the same time, analysis of the S100A8/A9 protein complex in clinical samples may help to distinguish between patients with bacterial versus viral pneumonia."

Journal • Infectious Disease • Interstitial Lung Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases • ELANE • S100A8 • S100A9

NRAS mutation drives excessive netosis and differentiation syndrome in acute promyelocytic leukemia (ASH 2025) - "Background Acute promyelocytic leukemia (APL) is highly curable with all-trans retinoic acid (ATRA) and arsenictrioxide (ATO)...Inhibitors targeting CXCR1/2 (Reparixin), NE(Sivelestat), MEK(Trametinib), PAD4(GSK484), and JAK1/2 (Ruxolitinib) were applied to evaluate their inhibitory effects onNETosis and differentiation...Targeting this pathway with reparixin or sivelestatattenuates NET formation without compromising cell differentiation, offering a promising therapeuticstrategy to mitigate DS-induced tissue damage while preserving anti-leukemic efficacy. These findingsprovide mechanistic insights into NRAS-driven inflammation in APL and support NETs-targeted therapyfor prophylaxis of DS."

Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Thrombosis • ANXA5 • CXCL8 • CXCR1 • ICAM1 • ITGAM • JAK1 • JAK2 • NRAS • VCAM1

Sodium Sivelestat With Mechanical Thrombectomy for Acute Stroke: A Pilot Study (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Xuanwu Hospital, Beijing | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

Effect of sivelestat on postoperative outcomes in patients with acute type A aortic dissection and hypoxemia: a retrospective analysis. (PubMed, Am J Cardiovasc Dis) - "In summary, patients with ATAAD and preoperative hypoxemia have lower postoperative PaO2/FiO2. Besides, sivelestat improves postoperative PaO2/FiO2, reduces inflammation, and shortens ventilation as well as ICU/hospital stay in ATAAD patients with preoperative hypoxemia."

Journal • Retrospective data • Acute Lung Injury • Critical care • Inflammation • Respiratory Diseases • CRP • IL6

Inhibition of neutrophil infiltration and NETosis ameliorates sepsis-induced cardiac injury and reduces myocardial inflammation and apoptosis. (PubMed, Int Immunopharmacol) - "Our findings indicate that NETosis and neutrophil infiltration are therapeutically actionable contributors in SIC. Strategies that inhibit NET formation, degrade extracellular DNA, or limit neutrophil recruitment were associated with reduced myocardial inflammation and apoptosis and partial preservation of systolic function. These results provide a theoretical basis for early diagnosis, timely intervention, and improved prognosis in SIC."

IO biomarker • Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • BAX • BCL2 • CASP3 • ELANE • IL1B • IL6 • TNFA

Deciphering Genotype-Phenotype Correlations and the Mechanism of the Action of Neutrophil Elastase Inhibitors during ELANE Associated Neutropenia Utilizing Molecular Modeling Software (ASH 2024) - "Molecular docking analysis of 4 small molecule, cell permeable NE inhibitors (MK0339, sivelestat, GW311616, BAY-678) and inactive control, BAY-677, revealed an alternative binding site for MK0339 inhibitor compared to all others. Conclusions : Molecular modeling software analysis of the effect of high- and low-risk mutations on NE protein structure may be key for understanding genotype-phenotype correlations for ELANE associated neutropenia. The current results of molecular docking and inhibitor-protein complex analysis via molecular modeling software correlates with our previous studies and suggests that MK0339 forms a much more stable complex with w-type and mutant NE protein compared to the other inhibitors tested, a valuable insight for developing a therapeutic agent for ELANE associated neutropenia."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • ELANE

Xiao Qing Long Tang ameliorates neutrophil extracellular trap-dendritic cells-T helper 17 cell axis in Neutrophilic Asthma. (PubMed, PLoS One) - "XQLT offered a promising treatment strategy for regulating the Nets-DCs-Th17 axis in NA."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL6 • MPO

Sivelestat for septic patients with acute respiratory distress syndrome: a systematic review and meta-analysis of a deadly duo. (PubMed, Front Med (Lausanne)) - "Further studies with well-designed protocols for administering sivelestat are needed to validate these findings. https://inplasy.com/wp-content/uploads/2025/06/INPLASY-Protocol-7969.pdf, identifier INPLASY202560111."

Journal • Retrospective data • Review • Acute Respiratory Distress Syndrome • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Septic Shock • ELANE

The protective effect of Sivirastat sodium on postoperative lung injury in patients undergoing cardiac surgery with concomitant pulmonary hypertension under extracorporeal circulation (ChiCTR) - P4 | N=60 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Guangxi Medical University; The First Affiliated Hospital of Guangxi Medical University

New P4 trial • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Effects of Comprehensive Lung-Protective Interventions on Postoperative Pulmonary Complications in Patients Undergoing Open-Heart Valve Surgery (ChiCTR) - P=N/A | N=250 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Guangxi Medical University; The First Affiliated Hospital of Guangxi Medical University

New trial • Cardiovascular • Heart Failure • CXCL8

Safety and Efficacy of Sivelestat Sodium in the Treatment of ARDS: A Prospective, Multicenter, Real-World Study (ChiCTR) - P=N/A | N=100 | Not yet recruiting | Sponsor: Wenjiang District People's Hospital, Chengdu; Wenjiang District People's Hospital, Chengdu

New trial • Real-world evidence • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

A Single-Center Prospective Observational Cohort Study on the Safety and Efficacy of Sodium Sivelestat in the Treatment of Primary or Secondary Brain Injury with ARDS (ChiCTR) - P4 | N=60 | Not yet recruiting | Sponsor: Mianyang Central Hospital; Mianyang Central Hospital

New P4 trial • CNS Disorders • Respiratory Diseases • Vascular Neurology

A study on the effects of Sivelestat Sodium injection in patients with COPD complicated by acute respiratory failure (ChiCTR) - P=N/A | N=160 | Not yet recruiting | Sponsor: Zhangzhou Hospital in Fujian Province; Zhangzhou Hospital in Fujian Province

New trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

SivelSep: Phase IIb Multicenter Randomized Controlled Trial Evaluating the Efficacy of Sivelestat in Patients With Septic Coagulopathy (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: University Hospital, Strasbourg, France

New P2 trial • Hematological Disorders • Septic Shock