REAnimation Low Immune Status Markers

NCT02638779 | Completed

• 2 other identifiers: 69HCL15_03792015-A01293-46
• Study Type: interventional
• Target: 552
• Locations: 1 country
• Sites: 1

Brief Summary

The fact that sepsis disrupts immune system homeostasis by inducing an initial cytokine storm, that participates to occurrence of organ failures and early death, followed by a compensatory anti-inflammatory response leading to immunosuppression, is now well established. This immunomodulating response results in a higher risk of secondary infections and is associated to 2/3 of deaths related to septic shocks. Follow up of patients' immune status with time is crucial to guide therapy management. Objective of REALISM project is to demonstrate existence of this immunosuppression phase, by providing strong epidemiologic data for septic shock patients, but also by extension to other situations of inflammatory aggressions like severe severe trauma or burns, or major surgery. This project will provide tools to predict occurrence of secondary infections and guide patient management by comparing innovating immunomonitoring tools to reference tests non already adapted to a routine patient management. Targeted populations are adult patients hospitalized for septic shock, severe trauma (including severe burn) or major surgery and healthy volunteers, whom blood samples will serve to validate reference intervals of the two reference tests.

Conditions

Septic Shock; Severe Trauma; Severe Burn; Major Surgery

Keywords

Septic shock; severe trauma; severe burn; major surgery; immunosuppression; Healthcare-Associated Infections

Outcome Measures

Primary Outcomes (1)

• Percentage of patients meeting the definition of of injury-induced-immunosuppression

  The immunosuppression status will be determined from two immunological reference tests: (1) lymphocyte proliferation in response to ex vivo T cell stimulation (adaptive immunity) (Poujol et al., 2014) and (2) the production of tumor necrosis factor (TNF) by monocytes in response to ex vivo stimulation by lipopolysaccharide (LPS) (innate immunity) (Duffy et al., 2014). The values measured will be defined as normal or abnormal, depending on whether they are within reference intervals (RI) derived from an independent set of healthy volunteers. For this purpose, the definition of immunosuppression will be: an abnormal result in at least one of the two "reference" tests (outside the reference intervals defining normal values), and on at least two consecutive samples. The same reference test must be abnormal in two successive samples examined for the patient to be considered immunosuppressed.

  Up to 2 months after injury

Secondary Outcomes (5)

• Proportion of patients with a deficiency of the innate or adaptive immunity

  Up to 2 months after injury

• Comparison of performance of the reference tests and new biomarkers for the diagnosis of immunosuppression

  Up to one week after injury

• Correlation between the immunosuppression status and the incidence of healthcare-associated infections

  Up to 28 days after injury

• Correlation between immunosuppression and mortality

  Up to 90 days after injury

• Comparison of immune status before and after surgery in the population of surgical patients

  Up to 2 months after surgery

Study Arms (1)

Blood sampling

EXPERIMENTAL

Blood sampling will be performed in all patients and healthy volunteers

Biological: Blood sampling

Interventions

Blood sampling BIOLOGICAL

Specific Blood sampling will be performed in patients and healthy volunteers

Blood sampling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or next of kin having been informed of the conditions of the study and having signed the informed consent form
• Patient hospitalized for :
• Septic shock
• Severe trauma (including severe burn)
• Major surgery
• Normal clinical examination
• Signed informed consent form
• Person with social security insurance

You may not qualify if:

• Patient with severe neutropenia (neutrophil count \<0.5 g/l)
• Patients receiving immunosuppressive therapy
• Patients receiving corticosteroids (IV or Per os)
• Use of therapeutic antibodies
• Patient with innate or acquired immune deficiency (for example severe combined immunodeficiency, HIV or AIDS, any stage)
• Patients for whom a care limitation was pronounced at time of enrolment
• Anticipated length of stay before discharge from the ICU is estimated at less than 48 hours
• Participation in an intervention study
• Pregnant or breastfeeding women
• Patient with no social security insurance, with restricted liberty or under legal protection
• Person with an infectious syndrome during the last 90 days
• Extreme physical stress within the last week
• Person having received within the last 90 days, a treatment based on
• Antivirals
• Antibiotics

Sponsors & Collaborators

• Hospices Civils de Lyon: lead
• Bioaster: collaborator
• Sanofi: collaborator
• BioMérieux: collaborator

Study Sites (1)

Service d'Anesthésie Réanimation - Hôpital Edouard Herriot

Lyon, 69437, France

Location

Related Publications (5)

• Rol ML, Venet F, Rimmele T, Moucadel V, Cortez P, Quemeneur L, Gardiner D, Griffiths A, Pachot A, Textoris J, Monneret G; REALISM study group. The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients. BMJ Open. 2017 Jun 21;7(6):e015734. doi: 10.1136/bmjopen-2016-015734.

  PMID: 28637738 RESULT

• Venet F, Textoris J, Blein S, Rol ML, Bodinier M, Canard B, Cortez P, Meunier B, Tan LK, Tipple C, Quemeneur L, Reynier F, Leissner P, Vedrine C, Bouffard Y, Delwarde B, Martin O, Girardot T, Truc C, Griffiths AD, Moucadel V, Pachot A, Monneret G, Rimmele T; REALISM study group. Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury. Crit Care Med. 2022 Apr 1;50(4):565-575. doi: 10.1097/CCM.0000000000005270.

  PMID: 34534131 RESULT

• Mallet F, Diouf L, Meunier B, Perret M, Reynier F, Leissner P, Quemeneur L, Griffiths AD, Moucadel V, Pachot A, Venet F, Monneret G, Lepape A, Rimmele T, Tan LK, Brengel-Pesce K, Textoris J. Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study. Front Immunol. 2021 Nov 2;12:698808. doi: 10.3389/fimmu.2021.698808. eCollection 2021.

  PMID: 34795661 RESULT

• Peronnet E, Blein S, Venet F, Cerrato E, Fleurie A, Llitjos JF, Kreitmann L, Terraz G, Conti F, Gossez M, Rimmele T, Textoris J, Lukaszewicz AC, Brengel-Pesce K, Monneret G; REAnimation Low Immune Status Marker (REALISM) Study Group. Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study. Crit Care Med. 2023 Jun 1;51(6):808-816. doi: 10.1097/CCM.0000000000005832. Epub 2023 Mar 14.

  PMID: 36917594 RESULT

• Bodinier M, Peronnet E, Brengel-Pesce K, Conti F, Rimmele T, Textoris J, Vedrine C, Quemeneur L, Griffiths AD, Tan LK, Venet F, Maucort-Boulch D, Monneret G; REALISM study group. Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients. Front Immunol. 2021 Nov 29;12:795052. doi: 10.3389/fimmu.2021.795052. eCollection 2021.

  PMID: 34912347 DERIVED

MeSH Terms

Conditions

Shock, Septic; Wounds and Injuries; Burns; Cross Infection

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 23, 2015
• Study Start: December 11, 2015
• Primary Completion: June 27, 2018
• Study Completion: June 27, 2018
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)