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Not yet recruitingNCT07214103SivelSepUpdated Aug 20, 2026

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

A Phase 2 interventional study of • Sivelestat intravenous infusion and NaCl intravenous infusion in Septic Shock and Coagulopathy, sponsored by University Hospital, Strasbourg, France. Not yet recruiting at 1 site in France. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-08-20.

Sponsored by University Hospital, Strasbourg, France · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

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).

02

Conditions studied

  • Septic Shock
  • Coagulopathy
03

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Active therapy

    • Sivelestat

    Drug: • Sivelestat intravenous infusion

  • Placebo comparator
    Placebo therapy

    • NaCl

    Drug: NaCl intravenous infusion

Interventions

  • 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)

  • DrugNaCl 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)

05

What researchers measure

Primary outcomes

  1. Plasma plasminogen levels

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

    Time frame: 24 hours

06

Study locations

1 site
  • Hôpitaux Universitaires de Strasbourg
    Strasbourg, France 67091, France
07

Registry details

Key details

Study ID
NCT07214103
Lead sponsor
University Hospital, Strasbourg, France
Responsible party
Sponsor
First posted
Oct 9, 2025
Start date
Aug 1, 2027 (estimated)
Primary completion
Aug 31, 2032 (estimated)
Completion
Dec 31, 2032 (estimated)
Last update
Aug 20, 2026

Study contacts

Julie HELMS, MD
Contact
Julie.helms@chru-strasbourg.fr
03 69 55 04 34 ext. 0033

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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