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RecruitingNCT04067674IMMUNOSEPSIS 4Updated Jul 13, 2026

Septic Shock-induced Immunosuppression

An observational study in Septic Shock, sponsored by Hospices Civils de Lyon. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-13.

Sponsored by Hospices Civils de Lyon · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
305
Ages
18 Years and older
Sex
All
01

Study 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 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:

  1. to identify the best biomarkers for sepsis-induced immunosuppression
  2. to evaluate ex vivo candidate treatments which could rejuvenate immune functions after septic shock
02

Conditions studied

  • Septic Shock

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03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients with septic shock

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
305 participants (estimated)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • 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

    Biological: Blood sampling

Interventions

  • BiologicalBlood sampling

    Blood sampling for biomarker measurement

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What researchers measure

Primary outcomes

  1. 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

    Time frame: at day 3 post septic shock diagnosis

Secondary outcomes

  1. 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

    Time frame: 28 days post septic shock diagnosis

  2. mortality rate

    Time frame: 28 days post septic shock diagnosis

06

Study locations

1 of 1 sites recruiting
  • Hôpital Edouard Herriot
    Lyon, 69003, France
    Recruiting
07

References and documents

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 36861044 ↗
  • Coudereau 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 ↗

Individual participant data

Plan to share: No

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Registry details

Key details

Study ID
NCT04067674
Lead sponsor
Hospices Civils de Lyon
Responsible party
Sponsor
First posted
Aug 26, 2019
Start date
Oct 21, 2019
Primary completion
Nov 21, 2026 (estimated)
Completion
Nov 21, 2026 (estimated)
Last update
Jul 13, 2026

Study contacts

Fabienne VENET, PhD
Contact
fabienne.venet@chu-lyon.fr
04 72 11 97 46
Valérie CERRO, CRA
Contact
valerie.cerro01@chu-lyon.fr
06 29 357 357
Fabienne VENET, PhD
principal investigator · Hospices Civils de Lyon

Oversight

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

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