Immunology of Septic Shock Clinical Trial
— IMMUNOSEPSISOfficial title:
Evaluation of Immunosuppression in Septic Shock: Biomarkers and Pharmacological Restoration (IMMUNOSEPSIS)
Septic syndromes (systemic inflammatory response associated with infection) remain a major
although largely under-recognized health care problem and represent the first cause of
mortality in intensive care units. 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 immunologic 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
(CMV or 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. Both arms of immunity (innate and adaptive) are indeed
markedly suppressed (including enhanced leukocyte apoptosis, lymphocyte anergy and
deactivated monocyte functions). New promising therapeutic avenues are currently emerging
from those recent findings such as adjunctive immunostimulation for the most
immunosuppressed patients. The prerequisite for immunostimulation administration (IFNg,
GM-CSF, IL-7) however relies on the investigators capacity in identifying the patients who
could benefit from it, as there is no clinical sign of immune dysfunctions. The main
objectives are:
1. to identify the best biomarkers for sepsis-induced immunosuppression and
2. to evaluate ex vivo whether drugs could rejuvenate immune functions.
| Status | Recruiting |
| Enrollment | 160 |
| Est. completion date | December 2016 |
| Est. primary completion date | December 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - septic shock is defined by an identifiable site of infection, persisting hypotension despite fluid resuscitation requiring vasopressor therapy, and evidence of a systemic inflammatory response Exclusion Criteria: - age < 18 - immunosuppressive disease (HIV, cancer, primary immune deficiency) - immunosuppressive treatment or corticoid treatment (dosage > 10mg/day or cumulative dose >700 mg equivalent prednisolone) - aplasia as defined by number of circulating neutrophils < 500 cells / mm3 - extracorporeal circulation during the month prior ICU admission |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| France | Hospices Civils de Lyon - Hopital Edouard Herriot | Lyon |
| Lead Sponsor | Collaborator |
|---|---|
| Hospices Civils de Lyon |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | mortality | 28 days post diagnosis | Yes | |
| Secondary | occurrence of nosocomial infection | 28 days post diagnosis | Yes | |
| Secondary | decreased monocyte HLA-DR expression | day 3 post diagnosis | No |