Monitoring of Septic Shock-induced Immunosuppression (IMMUNOSEPSIS 5)

Immunological and Clinical Monitoring of Patients With Septic Shock in Intensive Care Unit : In-depth Immunophenotyping of Circulating Immunoregulatory Cells During Sepsis

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.

Recent studies have described the induction of immunoregulatory cells (of myeloid and lymphoid origin) following septic shock and have revealed a similar induction kinetics across all subpopulations of regulatory cells. Nevertheless, these observations need to be confirmed and linked to the underlying mechanisms responsible for the induction of these cells (notably the activation of the inflammasome pathway), which remain largely unknown.

IMMUNOSEPSIS 5 study will therefore, as part of a prospective observational study involving a large cohort of patients, demonstrate the concurrent induction of all regulatory cell subpopulations following sepsis and the activation of the hyper-inflammatory response, including the inflammasome pathway. The association between these parameters and patient outcomes will also be assessed (death and/or the occurrence of a secondary infection).

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Biological: Additional tubes during routine blood sample collection

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: VENET FABIENNE, Pr; Phone Number: +33 4 72 11 97 46; Email: fabienne.venet@chu-lyon.fr
• Study Contact Backup: Name: SAUNIER Clarisse; Phone Number: +33 04 27 85 62 64; Email: clarisse.saunier@chu-lyon.fr

Study Locations

• France
  • Lyon, France, 69004
    • Service d'Anesthésie-Réanimation Groupement Hospitalier Nord Hôpital de la Croix Rousse
    • Contact: DELIGNETTE Marie-Charlotte, Dr; Phone Number: +33 4 26 10 90 70; Email: marie-charlotte.delignette@chu-lyon.fr
  • Lyon, France, 69004
    • Service de Médecine Intensive - Réanimation (MIR) Groupement Hospitalier Nord Hôpital de la Croix Rousse
    • Contact: BITKER Laurent, Dr; Phone Number: +33 4 26 10 92 69; Email: laurent.bitker@chu-lyon.fr
  • Lyon, France, 69437
    • Service civilo-militaire d'Anesthésie-Réanimation et Médecine Périopératoire - Groupement Hospitalier Centre
    • Contact: LUKASZEWICZ Anne-Claire, Pr; Phone Number: +33 4 72 11 96 86; Email: anne-claire.lukaszewicz@chu-lyon.fr
  • Lyon, France, 69437
    • Service de Médecine Intensive - Réanimation (MIR) - Groupement Hospitalier Centre
    • Contact: COUR Martin, Pr; Phone Number: +33 4 72 11 28 52; Email: martin.cour@chu-lyon.fr
  • Pierre-Bénite, France, 69495
    • Service d'Anesthésie-Réanimation-Médecine Intensive Groupement Hospitalier Sud Hôpital Lyon Sud - Bâtiment 3B
    • Contact: DARGENT Auguste, Dr; Phone Number: +33 4 78 86 14 76; Email: auguste.dargent@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will focus on adult patients admitted to the intensive care unit for the management of septic shock, defined according to the SEPSIS-3 criteria

Description

Inclusion Criteria:

• Men or women aged 18 years or over
• Hospitalised patients with septic shock that began less than 48 hours prior to screening, defined by:
• the presence of a diagnosed or suspected site of infection requiring microbiological sampling
• the need for vasopressor therapy to maintain a mean arterial pressure ≥ 65 mm Hg
• hyperlactataemia > 2 mmol/L (18 mg/dL) within 24 hours of the start of vasopressor therapy despite adequate fluid resuscitation (30 ml/kg).
• A patient or relative who has been informed of the study protocol and has not objected to participating in the study

Exclusion Criteria:

• Pregnant or breastfeeding women
• People not covered by a social security scheme or similar scheme
• Adults subject to legal guardianship (guardianship, curatorship)
• Patients with a language barrier
• Persons deprived of their liberty by a judicial or administrative decision
• Subjects participating in another interventional research study involving an exclusion period that is still ongoing at the time of pre-inclusion and which, in the investigator's judgement, may interfere with this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult patient with septic shock; Additional tubes will be collected for the study at the same time as routine blood sample procedure. No specific intervention will be performed for this study. Theses samples will be collected at the following timing : inclusion, J3, J5, J15, J25 (until patient is discharged from intensive care).	Biological: Additional tubes during routine blood sample collection; Four additional tubes will be collected during the blood sample carried out as part of standard of care : a 4 mL EDTA tube, a 2.5 mL heparin tube, a 5 mL CytoChex tube and a 4 mL PAXGENE tube.These samples will be taken at inclusion, J3, J5, J15, J25 (until patient is discharged from intensive care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of the mechanisms regulating the immune response during septic shock, and in particular study of regulatory cell subpopulations in a large cohort of adult patients with septic shock	Modification of immune parameters compared with normal values in particular proportion of immunoregulatory cells	Inclusion DAY 1 (within the 48 hours of starting vasopressor therapy) Between DAY 3 and DAY 4 Between DAY 5 and DAY 7 Between DAY 15 and DAY 20 Between DAY 25 and DAY 30

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Immune response; SEPSIS; Circulating immunoregulatory cells
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis
• Other Study ID Numbers: 69HCL25_0663

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No