Septic Shock-induced Immunosuppression (IMMUNOSEPSIS 4)

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:

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

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Biological: Blood sampling

• Study Type: Observational
• Enrollment (Anticipated): 305

Contacts and Locations

• Study Contact: Name: Fabienne VENET, PhD; Phone Number: 04 72 11 97 46; Email: fabienne.venet@chu-lyon.fr
• Study Contact Backup: Name: Valérie CERRO, CRA; Phone Number: 06 29 357 357; Email: valerie.cerro01@chu-lyon.fr

Study Locations

• France
  • Lyon, France, 69003
    • Recruiting
    • Hôpital Edouard Herriot
    • Contact: Fabienne VENET, PhD; Phone Number: + 33 4 72 11 97 46; Email: fabienne.venet@chu-lyon.fr
    • Principal Investigator: Fabienne VENET, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with septic shock

Description

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:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Blood sampling for biomarker measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	at day 3 post septic shock diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 days post septic shock diagnosis
mortality rate		28 days post septic shock diagnosis

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Fabienne VENET, PhD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 21, 2019
• Primary Completion (ANTICIPATED): November 21, 2024
• Study Completion (ANTICIPATED): November 21, 2024

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (ACTUAL): August 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 69HCL19_0071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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