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

NCT07214103 · tracked via the Priya Life Science France tracker

Sponsor

University Hospital, Strasbourg, France

Phase

Phase 2

Started

2027-08-01

Last updated

2026-08-20

Condition(s) studied

Septic ShockCoagulopathy

Investigational drug(s) / intervention(s)

• Sivelestat intravenous infusionNaCl intravenous infusion →

• 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)

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)

Study 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).

Eligibility

Sex

ALL

Min age

18 Years

Max age

85 Years

Healthy volunteers

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

Primary outcome measure(s)

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

Trial sites (1)

Facility	City	Region	Status
Hôpitaux Universitaires de Strasbourg	Strasbourg	France

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07214103 on ClinicalTrials.gov ↗ ← All trials in France