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

NCT07214103 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 9415
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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).

Conditions

Septic Shock; Coagulopathy

Outcome Measures

Primary Outcomes (1)

• Plasma plasminogen levels

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

  24 hours

Study Arms (2)

Active therapy

EXPERIMENTAL

• Sivelestat

Drug: • Sivelestat intravenous infusion

Placebo therapy

PLACEBO COMPARATOR

• NaCl

Drug: NaCl intravenous infusion

Interventions

• Sivelestat intravenous infusion DRUG

* 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)

Active therapy

NaCl intravenous infusion DRUG

* 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)

Placebo therapy

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Under legal protection (guardianship, curatorship, or legal safeguard)
• Pregnancy or breastfeeding
• Participation in another interventional drug clinical trial

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Hôpitaux Universitaires de Strasbourg

Strasbourg, France, 67091, France

Location

MeSH Terms

Conditions

Shock, Septic; Hemostatic Disorders

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Julie HELMS, MD

CONTACT

03 69 55 04 34; Julie.helms@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 9, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2032
• Last Updated: October 9, 2025

Record last verified: 2025-10

Locations

FR (1)