Clinical trial NCT04067674: Septic Shock-induced Immunosuppression
Official title: Evaluation of Immunosuppression in Septic Shock: Biomarkers and Pharmacological Restoration
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Septic Shock
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-08-26
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with septic shock

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


Eligibility criteria: 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

Primary outcomes:
measure: Major Histocompatibility Complex (MHC) class II expression rate
timeFrame: at day 3 post septic shock diagnosis
Secondary outcomes:
measure: ICU-acquired infections occurence
timeFrame: 28 days post septic shock diagnosis
measure: mortality rate
timeFrame: 28 days post septic shock diagnosis
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hôpital Edouard Herriot
Study officials:
affiliation: Hospices Civils de Lyon
name: Fabienne VENET, PhD
role: PRINCIPAL_INVESTIGATOR
References: