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NCT Number: NCT07214103

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

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).

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Key information

Conditions

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

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hôpitaux Universitaires de Strasbourg

Strasbourg, France, 67091

Location contact

Julie HELMS, MD

CONTACT

[email protected]

03 69 55 04 34 ext. 0033

Julie HELMS, MD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

• 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)

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)

Primary outcomes

Plasma plasminogen levels

Time frame: 24 hours

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

Study contacts

Contact information is provided by the study sponsor or research team.

Julie HELMS, MD

CONTACT

[email protected]

03 69 55 04 34 ext. 0033

Sponsors and collaborators

Lead sponsor

University Hospital, Strasbourg, France

Other

Registry information

Acronym: SivelSep

Important dates

Study start: 2026
Primary completion: 2032
Study completion: 2032
First posted: Oct 9, 2025
Registry last updated: Oct 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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