Septic ShockIMMUNOSEPSIS 4NCT04067674
Septic Shock-induced Immunosuppression
An observational study of Septic Shock, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Septic syndromes are a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units (ICU). While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings indicate that… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Blood sampling
- How many people
- 305 participants
- Where
- 1 siteFrance
- Study dates
- 21 Oct 2019to 21 Nov 2026
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with septic shock
Who may be able to join
- Age over 18 years
- Patient admitted to ICU
- Diagnosis of septic shock within less than 48h at time of screening defined by :
- Presence of a microbiologically diagnosed or suspected infection
- Initiation of a vasopressive treatment to maintain mean arterial blood pressure ≥ 65 mm Hg initiated during the first 48h after ICU admission
- Presence of an hyperlactatemia > 2 mmol/L (18 mg/dL) during the 24h before or after initiation of vasopressive treatment despite adequate volemic reanimation (30 ml/kg)
- Blood sample at D3/D4 available (lab working days)
- Non opposition to study participation obtained from patient or next of kin
Who cannot join
- Pregnant or breastfeeding woman
- Patient with no social security insurance, with restricted liberty or under legal protection
- Language barrier
- Patient taking part in interventional study about medicin that could interfere with biologic results
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, 1 recruiting
- Recruiting
Hôpital Edouard Herriot
Lyon, 69003
Fabienne VENET, PhD, + 33 4 72 11 97 46, fabienne.venet@chu-lyon.fr
Fabienne VENET, PhD
About this study
Official title: Evaluation of Immunosuppression in Septic Shock: Biomarkers and Pharmacological Restoration
Septic syndromes are a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units (ICU). While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short pro-inflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (cytomegalovirus (CMV) or Herpes Simplex Virus (HSV)) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. These alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. New promising therapeutic strategies are currently emerging from those recent findings such as adjunctive immunostimulation for the most immunosuppressed patients. The prerequisite for immunostimulation administration (Interferon gama (IFNg), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), interleukin 7 (IL-7)) however relies on clinicians' capacity to identify patients who could benefit the most from these immunoadjuvant therapies, as there is no clinical sign of immune dysfunctions.
In this context, the main objectives of IMMUNOSEPSIS 4 study are:
- to identify the best biomarkers for sepsis-induced immunosuppression
- to evaluate ex vivo candidate treatments which could rejuvenate immune functions after septic shock
- Conditions
- Septic Shock
- Being tested
- Blood sampling
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingBiological
Blood sampling for biomarker measurement
| Study group | Role | What they receive |
|---|---|---|
| Septic shock patients | Patients included in this cohort will have blood sampling for measurement of immune related biomarkers (immunophenotyping, functional tests, messenger ribonucleic acid (mRNA), circulating markers) in circulating blood and their associations with relevant clinical outcomes Receives: Biological: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Histocompatibility Complex (MHC) class II expression rate
Association between decreased MHC class II expression on monocytes at day 3 post diagnosis and occurrence of secondary ICU-acquired infections
Measured: at day 3 post septic shock diagnosis
Secondary outcomes (2)
ICU-acquired infections occurence
Association between decreased MHC class II expression on monocytes at day 3 post diagnosis and occurrence of secondary Intensive Care Unit (ICU)-acquired infections
Measured: 28 days post septic shock diagnosis
mortality rate
Measured: 28 days post septic shock diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start21 Oct 2019
- Primary completion21 Nov 2026 (estimated)
- Study completion21 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 305 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fabienne VENET, PhD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04067674
- Sponsor's protocol ID
- 69HCL19_0071
- Acronym
- IMMUNOSEPSIS 4
- Status last verified
- Jul 2026
- First submitted
- 22 Aug 2019
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Venet M, Bidar F, Derive M, Delwarde B, Monard C, Hengy B, Jolly L, Rimmele T, Lukaszewicz AC, Monneret G, Venet F. Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients. Crit Care Explor. 2023 Feb 24;5(3):e0869. doi: 10.1097/CCE.0000000000000869. eCollection 2023 Mar.
PubMed 36861044Coudereau R, Gossez M, Py BF, Henry T, Lukaszewicz AC, Monneret G, Venet F. Monitoring NLRP3 Inflammasome Activation and Exhaustion in Clinical Samples: A Refined Flow Cytometry Protocol for ASC Speck Formation Measurement Directly in Whole Blood after Ex Vivo Stimulation. Cells. 2022 Oct 20;11(20):3306. doi: 10.3390/cells11203306.
PubMed 36291172
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Immunosuppression in Septic Shock: Biomarkers and Pharmacological Restoration
- ClinicalTrials.gov ID
- NCT04067674
- Acronym / sponsor ID
- IMMUNOSEPSIS 4 / 69HCL19_0071
- Conditions
- Septic Shock
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 305 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 21 Oct 2019 (actual)
- Primary completion
- 21 Nov 2026 (estimated)
- Study completion
- 21 Nov 2026 (estimated)
- First posted
- 26 Aug 2019 (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.
Septic syndromes are a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units (ICU). While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short pro-inflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (cytomegalovirus (CMV) or Herpes Simplex Virus (HSV)) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. These alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. New promising therapeutic strategies are currently emerging from those recent findings such as adjunctive immunostimulation for the most immunosuppressed patients. The prerequisite for immunostimulation administration (Interferon gama (IFNg), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), interleukin 7 (IL-7)) however relies on clinicians' capacity to identify patients who could benefit the most from these immunoadjuvant therapies, as there is no clinical sign of immune dysfunctions.
In this context, the main objectives of IMMUNOSEPSIS 4 study are:
- to identify the best biomarkers for sepsis-induced immunosuppression
- to evaluate ex vivo candidate treatments which could rejuvenate immune functions after septic shock
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Septic shock patients | – | Biological: Blood samplingPatients included in this cohort will have blood sampling for measurement of immune related biomarkers (immunophenotyping, functional tests, messenger ribonucleic acid (mRNA), circulating markers) in circulating blood and their associations with relevant clinical outcomes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with septic shock
Key inclusion criteria (8 listed)
- Age over 18 years
- Patient admitted to ICU
- Diagnosis of septic shock within less than 48h at time of screening defined by :
- Presence of a microbiologically diagnosed or suspected infection
- Initiation of a vasopressive treatment to maintain mean arterial blood pressure ≥ 65 mm Hg initiated during the first 48h after ICU admission
Key exclusion criteria (4 listed)
- Pregnant or breastfeeding woman
- Patient with no social security insurance, with restricted liberty or under legal protection
- Language barrier
- Patient taking part in interventional study about medicin that could interfere with biologic results
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 |
|---|---|---|
| Blood samplingBlood sampling for biomarker measurement | Biological | Septic shock patients |
Primary outcome
Major Histocompatibility Complex (MHC) class II expression rate
Time frame: at day 3 post septic shock diagnosis
Association between decreased MHC class II expression on monocytes at day 3 post diagnosis and occurrence of secondary ICU-acquired infections
2 secondary outcomes
ICU-acquired infections occurence
Time frame: 28 days post septic shock diagnosis
mortality rate
Time frame: 28 days post septic shock diagnosis
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 13 Jul 2026.
- Derived from this study: PubMed 36861044Venet M, Bidar F, Derive M, Delwarde B, Monard C, Hengy B, Jolly L, Rimmele T, Lukaszewicz AC, Monneret G, Venet F. Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients. Crit Care Explor. 2023 Feb 24;5(3):e0869. doi: 10.1097/CCE.0000000000000869. eCollection 2023 Mar.
- Derived from this study: PubMed 36291172Coudereau R, Gossez M, Py BF, Henry T, Lukaszewicz AC, Monneret G, Venet F. Monitoring NLRP3 Inflammasome Activation and Exhaustion in Clinical Samples: A Refined Flow Cytometry Protocol for ASC Speck Formation Measurement Directly in Whole Blood after Ex Vivo Stimulation. Cells. 2022 Oct 20;11(20):3306. doi: 10.3390/cells11203306.
- Individual participant dataSharing planned: No
Related trials for Septic Shock
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Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
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Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis
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Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
Sepsis - to Reduce Mortality in the Intensive Care Unit, Septic Shock
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.
Fabienne VENET, PhD principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Septic Shock, run by Hospices Civils de Lyon 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 8 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 13 Jul 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Fabienne VENET, PhD (04 72 11 97 46, fabienne.venet@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Histocompatibility Complex (MHC) class II expression rate (time frame: at day 3 post septic shock diagnosis). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04067674, which also lists 2 linked publications.
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 13 Jul 2026.