Elaspol (sivelestat) / Ono Pharma - LARVOL DELTA

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

The multiple hit model of infantile and epileptic spasms: The 2025 update. (PubMed, Epilepsia Open) - "Infantile and epileptic spasms syndrome (IESS) manifests with epileptic spasms and negatively affects the infants' development due to cognitive and behavioral problems. We have optimized the multiple-hit rat model of IESS to screen for new therapies and present here an overview of the model, which models drug-resistant IESS due to structural etiology. We also present new data on the acute effects of five drugs on spasms and a comparative assessment of all the treatments tested in this model for effects and tolerability on spasms, developmental deficits, adult epilepsy, and tolerability."

Journal • CNS Disorders • Epilepsy • IGF1

Neutrophil extracellular traps exacerbate inflammatory arthritis by inhibiting γδ Treg cell differentiation via the AIM2 inflammasome. (PubMed, Redox Biol) - "Inhibition of NET formation with sivelestat (SVT) and CI-amidine restored the proportion of γδ Treg cells and had a therapeutic effect on CIA model mice...This process led to the pathological accumulation of reactive oxygen species, therefore directly inhibiting γδ Treg cell differentiation. Our study reveals the detailed mechanism through which NETs impeded γδ Treg cell differentiation and then exacerbated inflammatory arthritis, suggesting an underlying therapeutic strategy for inflammatory arthritis by targeting the NET-γδ Treg cell axis."

Journal • Immunology • Inflammatory Arthritis • Metabolic Disorders • Rheumatology

Therapeutic effect and mechanism of sivelestat sodium on acute lung injury: A randomized controlled trial. (PubMed, Medicine (Baltimore)) - "Sivelestat sodium can improve lung function, correct PaO2/FiO2, and promote rehabilitation in patients with acute lung injury, which may be related to the regulation of NLRP6, ICAM-1, and other inflammatory factors."

Clinical • Journal • Acute Lung Injury • Oncology • Ophthalmology • Respiratory Diseases • ICAM1 • IL1B • NLRP6 • TNFA

Research on the process and molecular mechanism of inhibiting serous ovarian cancer by PRTN3 and its inhibitor Sivelestat. (PubMed, J Ovarian Res) - "Whole exome sequencing and bioinformatics analysis identified PRTN3 as a potential molecular marker of serous ovarian cancer, and PRTN3 could significantly affect the prognosis of SOC patients. As an inhibitor of PRTN3, sivelestat can inhibit the expression of PRTN3 in SOC cell lines and reduce their migration ability in vitro. In vivo experiments showed that sivelestat can inhibit the growth of subcutaneous transplanted tumor in nude mice with certain safety."

Journal • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • Transplantation • Women's Health

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

New trial • Cardiovascular • Ischemic stroke

Prolonged immune activation in post-acute sequelae of SARS-CoV-2: neutrophil dynamics and therapeutic insights. (PubMed, Exp Mol Med) - "Among these, Sivelestat, a neutrophil elastase inhibitor, demonstrated the most pronounced efficacy, reducing PASC incidence and mortality, and markedly reducing neutrophil levels. These findings underscore the critical role of neutrophil activation in driving lung damage and chronic inflammation during PASC, offering promising therapeutic strategies for mitigating long-term COVID-19 sequelae."

Journal • Cognitive Disorders • Fatigue • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases • ELANE • FPR2 • MMP9 • S100A9

Lack of S100A8 impairs lung protective immunity against Streptococcus pneumoniae in mice (ERS 2025) - "Incubation of WT BALF with exogenous NE confirmed NE dependency of SP-D degradation in vitro, which was blocked in the presence of the NE-specific inhibitor sivelestat. Collectively, selective deletion of S100A8 severely disturbs lung protective immunity against S. pneumoniae in mice. At the same time, S100A8 protein levels in clinical samples may help to distinguish between patients with bacterial or viral pneumonia."

Preclinical • Infectious Disease • Interstitial Lung Disease • Pneumococcal Infections • Pneumonia • ELANE • S100A8 • S100A9

Sivelestat sodium: a novel therapeutic agent in a mouse model of acute exacerbation pulmonary fibrosis through multiple mechanisms. (PubMed, J Thorac Dis) - "Male C57BL/6J mice were used to establish the acute exacerbation of pulmonary fibrosis (AE-PF) mouse model through intratracheal instillation of bleomycin (BLM) followed by lipopolysaccharide (LPS). SIV demonstrates significant protective effects in AE-PF mice by mitigating inflammation, oxidative stress, apoptosis, and preserving epithelial barrier integrity. These findings suggest that SIV is a promising therapeutic candidate for the treatment of AE-IPF."

IO biomarker • Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • B Cell Lymphoma • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Lymphoma • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • BAX • CASP3 • ELANE • HMOX1 • IL1B • IL6 • TLR4

Sivelestat Treatment for Postoperative Organ Protection in Type A Aortic Dissection (clinicaltrials.gov) - P4 | N=236 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P4 trial • CXCL8

TLR9/NF-κB-mediated dendritic cell activation by neutrophil extracellular traps drives pathogenesis in experimental cerebral malaria. (PubMed, J Neuroinflammation) - "Inhibiting NETs with Sivelestat effectively impeded the onset and progression of CM in the PbA infected mice. Collectively, our results indicated that neutrophil cell death (NETosis) induced TLR9-dependent DC activation and pathogenic CD8+ T cell responses, revealing that the NETs-TLR9/NF-κB-DC-CD8+ T cell axis may provide novel insights into the immunopathogenic mechanisms of CM."

Journal • Infectious Disease • Inflammation • Malaria • CD8 • TLR4 • TLR7 • TLR9

2023-LCYJ-MS-26: Efficacy and Safety of Sivelestat in Preventing Postoperative Acute Lung Injury or Acute Respiratory Distress Syndrome After Cardiac Surgery (clinicaltrials.gov) - P3 | N=382 | Completed | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Jul 2025 | Trial primary completion date: Jun 2026 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • Acute Lung Injury • Acute Respiratory Distress Syndrome • Cardiovascular • Heart Failure • Pulmonary Disease • Respiratory Diseases

Effect of sivelestat sodium on the incidence of ventilator-associated pneumonia in patients with sepsis and ARDS. (PubMed, Front Med (Lausanne)) - "Sivelestat sodium therapy was associated with a reduced incidence of VAP and a shorter ICU stay in patients with ARDS. However, there was no significant benefit on 28 days survival or total hospital stay."

Journal • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • CRP • IL6