NCT07214103

Phase IIb Multicenter Randomized Controlled Trial Evaluating the Efficacy of Sivelestat in Patients With Septic Coagulopathy

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: University Hospital, Strasbourg, France · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Sepsis-induced disseminated intravascular coagulation (DIC) is a severe complication occurring in one-third of patients with septic shock, for which no specific treatment currently exists. It results from excessive systemic activation of coagulation and impaired fibrinolysis, leading to the development of disseminated microthromboses. We have recently demonstrated: 1) the contribution of NETs to the hypercoagulability observed in DIC, and 2) the role of neutrophil elastase-bound to NET DNA-in degrading plasminogen, a key factor limiting fibrinolysis and thus preventing the lysis of microthrombi in DIC. Sivelestat is a neutrophil elastase inhibitor used in Japan for the treatment of acute respiratory distress syndrome (ARDS). It has the potential to inhibit: 1) neutrophil activation and the release of inflammatory mediators, and 2) plasminogen degradation, which drives fibrinolytic failure. A recent meta-analysis including 2,050 patients across 15 studies showed that Sivelestat reduced ARDS patient mortality at day 28-30 (RR = 0.81, 95% CI = 0.66-0.98, p = 0.03), decreased mechanical ventilation duration and ICU length of stay, and improved oxygenation. We propose to conduct a multicenter, double-blind, placebo-controlled phase IIb trial evaluating the efficacy of Sivelestat in restoring fibrinolysis in patients with septic shock complicated by coagulopathy, defined by a positive SIC score (≥ 4 points).

Conditions

• Septic Shock
• Coagulopathy

Interventions

Type	Name	Description
DRUG	• Sivelestat intravenous infusion	* Intervention: Sivelestat 0.20 mg/kg/h via continuous intravenous infusion (IVSE) for 72 hours * Anticoagulation: Unfractionated heparin (UFH) at a minimum dose of 100 IU/24h (or higher if required)
DRUG	NaCl intravenous infusion	* Intervention: NaCl 0.9% (normal saline) via continuous intravenous infusion (IVSE) at the same rate as the experimental group for 72 hours * Anticoagulation: Unfractionated heparin (UFH) at a minimum dose of 100 IU/24h (or higher if required)

Timeline

• Start date: 2026-03-01
• Primary completion: 2032-12-31
• Completion: 2032-12-31
• First posted: 2025-10-09
• Last updated: 2025-10-09

Locations

1 site across 1 country: France