Clinical trial NCT02638779: REAnimation Low Immune Status Markers
Official title: REAnimation Low Immune Status Markers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Shock
Severe Trauma
Severe Burn
Major Surgery
Keywords: Septic shock
severe trauma
severe burn
major surgery
immunosuppression
Healthcare-Associated Infections
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
Collaborators: name: Bioaster
name: BioMérieux
name: Sanofi
First posted: 2015-12-23
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: Inclusion criteria for patients

* 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

Inclusion criteria for healthy volunteers

* Normal clinical examination
* Signed informed consent form
* Person with social security insurance

Exclusion criteria for patients

* 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
* Hematological disease under treatment, or treated within 5 years before inclusion
* End of chemotherapy within the 6 months prior to inclusion
* 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
* Extra-corporeal circulation in the month preceding inclusion in case of cardiac surgery
* Pregnant or breastfeeding women
* Patient with no social security insurance, with restricted liberty or under legal protection

Exclusion criteria for healthy volunteers

* 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
  * Antiparasitics
  * Antifungics
* Person having received within the last 15 days, a treatment based on non-steroidal anti-inflammatory drugs (NSAIDs)
* Person having received within the last 24 months, a treatment based on

  * Immunosuppressive therapy
  * Corticosteroids (IV or Per os)
  * Therapeutic antibodies
  * Chemotherapy
* History of :

  * innate or acquired immune deficiency
  * Hematological disease
  * Solid tumor
  * Severe chronic disease
  * Surgery or hospitalization within the last 2 years
  * Pregnancy within the last year
* Participation to a phase I clinical assay during the last year
* Pregnant or breastfeeding women
* Person with restricted liberty or under legal protection

Primary outcomes:
measure: Percentage of patients meeting the definition of of injury-induced-immunosuppression
timeFrame: Up to 2 months after injury
Secondary outcomes:
measure: Proportion of patients with a deficiency of the innate or adaptive immunity
timeFrame: Up to 2 months after injury
measure: Comparison of performance of the reference tests and new biomarkers for the diagnosis of immunosuppression
timeFrame: Up to one week after injury
measure: Correlation between the immunosuppression status and the incidence of healthcare-associated infections
timeFrame: Up to 28 days after injury
measure: Correlation between immunosuppression and mortality
timeFrame: Up to 90 days after injury
measure: Comparison of immune status before and after surgery in the population of surgical patients
timeFrame: Up to 2 months after surgery
Other outcomes:
Locations:
city: LYON cedex 03
country: France
facility: Service d'Anesthésie Réanimation - Hôpital Edouard Herriot
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.