Septic ShockPhase 2SivelSepNCT07214103
Phase IIb Multicenter Randomized Controlled Trial Evaluating the Efficacy of Sivelestat in Patients With Septic Coagulopathy
A Phase 2 study testing • Sivelestat intravenous infusion and NaCl intravenous infusion in people with Septic Shock and Coagulopathy, run by University Hospital, Strasbourg, France at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Septic Shock, Coagulopathy
- What is being tested?
- • Sivelestat intravenous infusion and NaCl intravenous infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- 1 Aug 2027to 31 Dec 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- Under legal protection (guardianship, curatorship, or legal safeguard)
- Pregnancy or breastfeeding
- Participation in another interventional drug clinical trial
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Hôpitaux Universitaires de Strasbourg
Strasbourg, France, 67091
Julie HELMS, MD, 03 69 55 04 34 ext. 0033, Julie.helms@chru-strasbourg.fr
Julie HELMS, MD
About this study
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
- Being tested
- • Sivelestat intravenous infusion, NaCl intravenous infusion
- Medical subject headings
- Shock, Septic, Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
• Sivelestat intravenous infusionDrug
- 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 infusionDrug
- 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 group | Role | What they receive |
|---|---|---|
| Active therapy | Experimental | • Sivelestat Receives: Drug: • Sivelestat intravenous infusion |
| Placebo therapy | Placebo comparator | • NaCl Receives: Drug: NaCl intravenous infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma plasminogen levels
Change in plasma plasminogen levels after 24 hours of treatment with either placebo or Sivelestat.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2025
- Study start1 Aug 2027 (estimated)
- Primary completion31 Aug 2032 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07214103
- Sponsor's protocol ID
- 9415
- Acronym
- SivelSep
- Status last verified
- Aug 2026
- First submitted
- 2 Oct 2025
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIb Multicenter Randomized Controlled Trial Evaluating the Efficacy of Sivelestat in Patients With Septic Coagulopathy
- ClinicalTrials.gov ID
- NCT07214103
- Acronym / sponsor ID
- SivelSep / 9415
- Conditions
- Septic Shock, Coagulopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 1 Aug 2027 (estimated)
- Primary completion
- 31 Aug 2032 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 9 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active therapy | Experimental | Drug: • Sivelestat intravenous infusion• Sivelestat |
| Placebo therapy | Placebo comparator | Drug: NaCl intravenous infusion• NaCl |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults aged 18 to 85 years
- Patient (male or female) admitted to the ICU with:
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| • 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) | Drug | Active therapy |
| 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) | Drug | Placebo therapy |
Primary outcome
Plasma plasminogen levels
Time frame: 24 hours
Change in plasma plasminogen levels after 24 hours of treatment with either placebo or Sivelestat.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing • Sivelestat intravenous infusion and NaCl intravenous infusion in people with Septic Shock and Coagulopathy, run by University Hospital, Strasbourg, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julie HELMS, MD (03 69 55 04 34 ext. 0033, Julie.helms@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma plasminogen levels (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.