Septic Shock-induced Immunosuppression

Septic Shock Clinical Trial

— IMMUNOSEPSIS 4  

Official title:

Evaluation of Immunosuppression in Septic Shock: Biomarkers and Pharmacological Restoration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04067674
• Other study ID #: 69HCL19_0071
• Status: Recruiting
• Start date: October 21, 2019
• Est. completion date: November 21, 2024

Study information

• Verified date: June 2024
• Source: Hospices Civils de Lyon
• Contact: Fabienne VENET, PhD
• Phone: 04 72 11 97 46
• Email: fabienne.venet[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 305
• Est. completion date: November 21, 2024
• Est. primary completion date: November 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Biological:
• Blood sampling
Blood sampling for biomarker measurement

Locations

Country	Name	City	State
France	Hôpital Edouard Herriot	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	mortality rate		28 days post septic shock diagnosis