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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05], Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Direction Générale de l'Offre de Soins (DGOS)

External identifiers

EU CT number

2025-523397-16-00

ClinicalTrials.gov

NCT07214103

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of Sivelestat, compared with placebo, in restoring fibrinolysis in septic shock patients with coagulopathy defined by a positive CIS score (≥ 4 points)

Secondary objectives 2

1. To obtain the first data on the efficacy of Sivelestat in patients in septic shock with coagulopathy, in the treatment arm compared with placebo
2. To evaluate the safety and tolerability of Sivelestat in patients with septic shock and coagulopathy in the treatment arm (0.2 mg/kg/h) over the study period, compared with placebo

Conditions and MedDRA coding

Septic Coagulopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adults aged 18 to 85
2. Patient (male or female) admitted to intensive care with: septic shock as defined by Sepsis-3 criteria [7]: o patient with acute life-threatening organ dysfunction(s) related to suspected or proven infection, requiring vasopressor support to maintain a mean arterial pressure ≥ 65 mmHg, and a serum lactate level > 2 mmol/L in the absence of hypovolaemia o and coagulopathy defined by a SIC score ≥ 4 points [21, 22]
3. Randomisation within 12 hours of diagnosis of coagulopathy (positive SIC score)
4. Patient affiliated with a national health insurance system.
5. 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.
6. - For women of childbearing age (negative blood pregnancy test)

Exclusion criteria 10

1. History of hypersensitivity reaction to Sivelestat (only contraindication to Sivelestat)
2. Patient weight > 100 kg
3. Severe chronic liver disease (Child-Pugh C)
4. Contraindication to the use of unfractionated heparin
5. Patient moribund on the day of randomisation
6. Limitation of active therapeutic interventions at the time of study inclusion
7. Under legal protection (guardianship, curatorship, or legal safeguard)
8. Pregnancy (positive blood pregnancy test) or breastfeeding
9. - Participation in another interventional drug clinical trial
10. - History of HIT (heparin-induced thrombocytopenia)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in plasma plasminogen levels after 24 hours of treatment with placebo or Sivelestat

Secondary endpoints 4

1. Confirmatory secondary endpoints (mechanism-related) to document the biological and pathophysiological consistency of the treatment effect. Changes in coagulation and fibrinolysis biomarkers: • CBC, PT, antithrombin, D-dimers, plasminogen, plasmin, tPA, PAI-1, PAP measured on Day 1 (baseline), Day 2, Day 3, Day 4, and Day 7. • Normalization of the SIC score < 4 at Day 7. These endpoints will help document the kinetics of restoration of the coagulation–fibrinolysis balance under treatment
2. Exploratory clinical secondary endpoints These endpoints aim to explore the potential impact of the treatment on the clinical course of sepsis and organ dysfunction. • Sepsis Support Index (SSI) up to Day 28 • Penalized SSI up to Day 28 • SOFA score at Day 1, Day 2, Day 3, Day 4, and Day 7 • KDIGO criteria and use of renal replacement therapy at Day 7 • Thrombotic and hemorrhagic complications at Day 7
3. Exploratory resource use and prognostic endpoints to explore a potential impact on the care trajectory. • Number of days free from mechanical ventilation at Day 28 • Number of days free from vasopressor support at Day 28 • Number of days free from ICU stay at Day 28 • Number of days free from hospitalization at Day 90 • Mortality at Day 7, Day 28, and Day 90 These endpoints will be analyzed for exploratory purposes only, in order to generate hypotheses for future confirmatory trials
4. Safety Safety will be assessed by: • systematic collection of adverse events (AEs) • collection of serious adverse events (SAEs) with particular attention paid to hemorrhagic and thrombotic events, given the mechanism of action of the treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

HELMS Julie

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

HELMS Julie

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications