Septic Shock-induced Immunosuppression

Recruiting

• Conditions: Septic Shock
• Interventions: Biological: Blood sampling

• Registration Number: NCT04067674
• Lead Sponsor: Hospices Civils de Lyon

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-22
• Study First Submitted QC: 2019-08-22
• Study First Posted: 2019-08-26
• Study Start: 2019-10-21
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-11
• Last Update Posted: 2024-06-12
• Primary Completion: 2024-11-21
• Study Completion: 2024-11-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 305

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

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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

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Septic shock patients	Blood sampling	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

Primary Outcome Measures

Name	Time	Method
Major Histocompatibility Complex (MHC) class II expression rate	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

Secondary Outcome Measures

Name	Time	Method
mortality rate	28 days post septic shock diagnosis
ICU-acquired infections occurence	28 days post septic shock diagnosis	Association between decreased MHC class II expression on monocytes at day 3 post diagnosis and occurrence of secondary Intensive Care Unit (ICU)-acquired infections

Trial Locations

Locations (1)

Hôpital Edouard Herriot; 🇫🇷 Lyon, France