Hepcidin: a Prognostic Marker of Morbidity and Mortality in Severe Sepsis?

Severe Sepsis or Septic Shock Clinical Trial

— HEP-SEPSIS  

Official title:

Hepcidin: a Prognostic Marker of Morbidity and Mortality in Severe Sepsis?

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03682003
• Other study ID #: 35RC13_9906_HEP-SEPSIS
• Status: Active, not recruiting
• Start date: October 1, 2014
• Est. completion date: December 1, 2019

Study information

• Verified date: September 2018
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 114
• Est. completion date: December 1, 2019
• Est. primary completion date: July 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis
• Severe Sepsis or Septic Shock
• Shock, Septic
• Toxemia

Intervention

Diagnostic Test:
• blood diagnostic tests
blood tests are performed to determine hepcidin, IL-6, CRP, PCT, serum iron, ferritin, transferrin and transferrin saturation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of plasma hepcidin assayed at admission to intensive care on mortality at D28 in patients with severe sepsis.	Sensitivity of plasma hepcidin assayed at admission to intensive care on mortality at D28 in patients with severe sepsis.	day 28
Secondary	mortality at day 90	mortality at day 90	day 90
Secondary	occurrence of care-related infections as defined by the Center for Disease Control and Prevention during hospitalization	occurrence of care-related infections as defined by the Center for Disease Control and Prevention during hospitalization	day 90
Secondary	occurrence of new organ failure (SOFA) or the aggravation of an existing organ failure on seventh day of sepsis	occurrence of new organ failure (SOFA) or the aggravation of an existing organ failure on seventh day of sepsis	day 90