Septic Shock-induced Immunosuppression

NCT04067674 | Recruiting

• 1 other identifier: 69HCL19_0071
• Study Type: observational
• Target: 305
• Locations: 1 country
• Sites: 1

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

Conditions

Septic Shock

Outcome Measures

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

  at day 3 post septic shock diagnosis

Secondary Outcomes (2)

• ICU-acquired infections occurence

  28 days post septic shock diagnosis

• mortality rate

  28 days post septic shock diagnosis

Study Arms (1)

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

Blood sampling BIOLOGICAL

Blood sampling for biomarker measurement

Septic shock patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with septic shock

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Edouard Herriot

Lyon, 69003, France

RECRUITING

Related Publications (2)

• 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.

  PMID: 36861044 DERIVED

• 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.

  PMID: 36291172 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Shock, Septic

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Fabienne VENET, PhD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabienne VENET, PhD

CONTACT

04 72 11 97 46; fabienne.venet@chu-lyon.fr

Valérie CERRO, CRA

CONTACT

06 29 357 357; valerie.cerro01@chu-lyon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 26, 2019
• Study Start: October 21, 2019
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: June 12, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)