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

Not Applicable

Not yet recruiting

• Conditions: Septic Shock; Coagulopathy
• Interventions: Drug: • Sivelestat intravenous infusion; Drug: NaCl intravenous infusion

• Registration Number: NCT07214103
• Lead Sponsor: University Hospital, Strasbourg, France

Brief 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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-02
• Study First Submitted QC: 2025-10-02
• Last Update Submitted: 2025-10-02
• Study First Posted: 2025-10-09
• Last Update Posted: 2025-10-09
• Study Start: 2026-03-01
• Primary Completion: 2032-12-31
• Study Completion: 2032-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Adults aged 18 to 85 years

• Patient (male or female) admitted to the ICU with:

  • Septic shock defined by Sepsis-3 criteria: acute, life-threatening organ dysfunction related to a suspected or confirmed infection, requiring vasopressor support to maintain a mean arterial pressure ≥ 65 mmHg and a serum lactate level > 2 mmol/L despite adequate fluid resuscitation.
  • Coagulopathy defined by a SIC score ≥ 4 points.

• Randomization within 12 hours after the diagnosis of coagulopathy (positive SIC score).

• Patient affiliated with a national health insurance system.

• Written informed consent: freely given, dated, and signed.

  • By the patient
  • Or by a legal representative if the patient is unable to provide consent.
  • Or through an emergency inclusion procedure if the patient is unable to consent and no family member is available

Exclusion Criteria

• History of hypersensitivity reaction to Sivelestat (the only contraindication for Sivelestat)
• Patient weight > 100 kg
• Severe chronic liver disease (Child-Pugh C)
• Contraindication to the use of unfractionated heparin
• Moribund patient at the time of randomization
• Limitation of active therapeutic interventions at the time of study inclusion
• Under legal protection (guardianship, curatorship, or legal safeguard)
• Pregnancy or breastfeeding
• Participation in another interventional drug clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active therapy	• Sivelestat intravenous infusion	• Sivelestat
Placebo therapy	NaCl intravenous infusion	• NaCl

Primary Outcome Measures

Name	Time	Method
Plasma plasminogen levels	24 hours	Change in plasma plasminogen levels after 24 hours of treatment with either placebo or Sivelestat.

Trial Locations

Locations (1)

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France, France