Clinical trial NCT03682003: Hepcidin: a Prognostic Marker of Morbidity and Mortality in Severe Sepsis?
Official title: Hepcidin: a Prognostic Marker of Morbidity and Mortality in Severe Sepsis?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Severe Sepsis or Septic Shock
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2018-09-24
Enrollment: 114
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: Man or woman, older than or equal to 18 years, with severe sepsis or septic shock according to the criteria of the American College of Chest Physicians / Society of Critical Care Medicine (ACCP / SCCM),

Brief summary: Many biomarkers have been evaluated in sepsis, especially for prognostic purposes, but none has yet been shown to have sufficient sensitivity or specificity for routine use in clinical practice. However, highlighting a biomarker facilitating the evaluation of the severity of sepsis remains relevant in a pathology where survival is largely conditioned by the initiation of an early and adapted treatment. Recent evidence suggests that hepcidin, which is the key hormone for systemic regulation of iron metabolism, may be an interesting prognostic biomarker. The synthesis of this peptide is regulated by the iron stocks of the body, erythropoiesis, but also inflammation. The mechanisms inducing the expression of hepcidin during inflammation are multiple: interleukin-6 (IL-6) in particular, pro-inflammatory cytokine is a strong inducer of hepcidin. In addition, its expression is increased by the effect of lipopolysaccharide via Toll-like receptors . In septic patients, elevated levels of hepcidin or pro-hepcidin have been reported . A new role for hepcidin in the control of inflammatory and / or immune response has recently been reported. Thus, in a model of murine septic shock, the deleterious character of a lack of expression of hepcidin could be demonstrated . In humans, hepcidinemia has been shown to be a predictive factor in the development of immunotolerance in hepatic transplant patients. Hepcidin therefore plays a major role in the regulation of the inflammatory and / or immune response and in particular during sepsis. The investigators therefore hypothesize that hepcidin could be the marker of an adverse prognosis in septic patients expressing this

Detailed description: Many biomarkers have been evaluated in sepsis, especially for prognostic purposes, but none has yet been shown to have sufficient sensitivity or specificity for routine use in clinical practice. However, highlighting a biomarker facilitating the evaluation of the severity of sepsis remains relevant in a pathology where survival is largely conditioned by the initiation of an early and adapted treatment. Recent evidence suggests that hepcidin, which is the key hormone for systemic regulation of iron metabolism, may be an interesting prognostic biomarker. The synthesis of this peptide is regulated by the iron stocks of the body, erythropoiesis, but also inflammation. The mechanisms inducing the expression of hepcidin during inflammation are multiple: interleukin-6 (IL-6) in particular, pro-inflammatory cytokine is a strong inducer of hepcidin. In addition, its expression is increased by the effect of lipopolysaccharide via Toll-like receptors . In septic patients, elevated levels of hepcidin or pro-hepcidin have been reported . A new role for hepcidin in the control of inflammatory and / or immune response has recently been reported. Thus, in a model of murine septic shock, the deleterious character of a lack of expression of hepcidin could be demonstrated . In humans, hepcidinemia has been shown to be a predictive factor in the development of immunotolerance in hepatic transplant patients. Hepcidin therefore plays a major role in the regulation of the inflammatory and / or immune response and in particular during sepsis. The investigators therefore hypothesize that hepcidin could be the marker of an adverse prognosis in septic patients expressing this.

Primary endpoint is to evaluate the prognostic value of plasma hepcidin assayed on admission to intensive care on mortality at D28 in severe sepsis.

Sensitivity of plasma hepcidin assayed at admission to intensive care on mortality at D28 in patients with severe sepsis.

In a first step, a search for the hepcidin threshold value with the best sensitivity and specificity to predict death on D28 will be performed using a receiver operating characteristics (ROC) curve. This threshold value will be used to evaluate the primary endpoint and also determine specificity and positive and negative predictive values.

Eligibility criteria: Inclusion Criteria:

* man or woman,
* older than or equal to 18 years, in severe sepsis or septic shock according to the criteria of the American College of Chest Physicians / Society of Critical Care Medicine (ACCP / SCCM),
* no opposition from the patient, a relative or the legal representative

Exclusion Criteria:

* pregnant or lactating woman,
* patient with hemochromatosis.

Primary outcomes:
measure: Sensitivity of plasma hepcidin assayed at admission to intensive care on mortality at D28 in patients with severe sepsis.
timeFrame: day 28
Secondary outcomes:
measure: mortality at day 90
timeFrame: day 90
measure: occurrence of care-related infections as defined by the Center for Disease Control and Prevention during hospitalization
timeFrame: day 90
measure: occurrence of new organ failure (SOFA) or the aggravation of an existing organ failure on seventh day of sepsis
timeFrame: day 90
Other outcomes:
Locations:
Study officials:
affiliation: Rennes University Hospital
name: Nicolas Nesseler, MD
role: PRINCIPAL_INVESTIGATOR
References: