Utility of Presepsin in Children Sepsis

Diagnostic and Prognostic Utility of Presepsin for Sepsis and Systemic Inflammatory Response Syndrome in Children

Presepsin (formerly CD14), is a glycoprotein receptor occurring at the surface of monocytes/macrophages. CD14 binds to lipopolysaccharide (LPS) complexes and LPS binding protein (LPB), which triggers the activation of toll-like receptor 4 (TLR4), resulting in the production of numerous pro-inflammatory cytokines. Following Presepsin activation by bacterial products, the CD14 complex is released in the circulation as its soluble form (sCD14), which in turn is cleaved by a plasma protease to generate a sCD14 fragment called sCD14-subtype (sCD14- ST). Plasma levels of sCD14 can be measured using an automated chemo-luminescent assay (PATHFAST).

Study Overview

• Status: Unknown
• Conditions: Sepsis Syndrome
• Intervention / Treatment: Other: therapy sepsis

Detailed Description

Severe sepsis and septic shock represent major challenges of modern intensive care medicine, and still recently published international guidelines demand ongoing research about the pathophysiology, diagnostics and treatment. Currently, the diagnosis of sepsis is based on the presence of systemic inflammatory response syndrome (SIRS) criteria in the presence of a known infection. However, non-infectious SIRS associated with acute tissue injury and innate immune activation can induce clinical syndromes analogous to sepsis, including multiple trauma, pancreatitis, burns, and autoimmune diseases.

Within the field of infectious diseases, a biomarker may be used for identifying a high risk group or predisposing condition, as an aid to identification of the disease, or to direct therapy and stratify patients according to their specific risk factors, and/or as an aid to therapeutic management in order to avoid relapse of infection. Within the recent years, dozens of potential biomarkers of infection have been described. The diagnostic performance of biomarkers is usually measured in terms of sensitivity, specificity, and by likelihood ratios and area under the ROC (Receiver Operating Characteristics) curves.

Recently, several researches devolved their interest in discovering pathways involved in the innate immunity. Mediators involved in the recognition and elimination of bacterial endotoxins have been identified as new candidate biomarkers of sepsis, namely lipopolysaccharide binding protein (LBP) and soluble fractions of the membrane cluster of differentiation 14 (mCD14). Membrane CD14 is a multifunctional glycosylphosphatidylinositol-anchored membrane protein (cell surface glycoprotein), constitutively expressed by various cells, including monocytes, macrophages, neutrophils, etc. CD14 is a pattern recognition receptor for bacterial molecules, namely lipopolysaccharides (LPS) from Gram-negative bacteria and peptidoglycans together with lipoteichoic acid from Gram-positive bacteria. CD14 is crucial in activating the toll-like receptor 4 (TLR4)-specific proinflammatory signaling cascade and ultimately, initiating the inflammatory reaction against invading microorganisms. In the course of inflammatory reaction, plasma protease activity generates soluble CD14 fragments (sCD14), presepsin.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Czech Republic
  • Brno, Czech Republic, 625 00
    • Faculty hospital Brno

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Childrens with SIRS or septic state who will be admitted to the Department of Anesthesia and Intensive Care of the University Children´s Hospital Brno, Czech Republic. Infections, sepsis, severe sepsis, septic shock and multiple organ dysfunction syndrome (MODS) will be defined according to commonly used criteria - by International pediatric sepsis consensus conference. The samples from children undergoing elective surgery will be used as a controls, i.e. samples from patients without signs of infection.

Description

Sepsis/SIRS Patients

Inclusion Criteria:

• children aged 1 - 216 months
• clinical data to enable classification into sepsis or SIRS
• written informed consent by the legally authorized representative

Exclusion Criteria:

• no informed consent

Control

Inclusion Criteria:

• children aged 1 - 216 months
• does not meet clinical criteria for sepsis or SIRS
• written informed consent by the legally authorized representative

Exclusion Criteria:

• no informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
children with sepsis, SIRS; Data will be collected and analyzed from childrens with SIRS or septic state who will be admitted to the Department of Anesthesia and Intensive Care of the University Children´s Hospital Brno, Czech Republic. Infections, sepsis, severe sepsis, septic shock and multiple organ dysfunction syndrome (MODS) will be defined according to commonly used criteria - by International pediatric sepsis consensus conference.	Other: therapy sepsis; Treatment of sepsis varies depending on the site and cause of the initial infection, the organs affected and the extent of any damage
control group, healthy children; The samples children undergoing elective surgery will be used as a controls, i.e. samples from patients without signs of infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of presepsin	Assessed the presepsin diagnostic accuracy of presepsin in diagnosing children sepsis and in discriminating systemic inflammatory response syndrome (SIRS) from sepsis. Diagnostic accuracies presented as area under the curve (AUC) for sCD14-ST.	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of presepsin	Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to other inflammatory markers in children with SIRS and suspected sepsis or septic shock. Receiver operating characteristic (ROC) curve analysis will performed for presepsin and compared to ROC curve analysis of current available infection biomarkers.	up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Sepsis mortality in children remains high despite advances in diagnosis and treatment. Early identification and risk stratification is a key point in the triage of patients with sepsis. The aim of the study is identifying and testing of presepsin with improved sensitivity and specifity for the presence of sepsis, and prediction of morbidity and mortality.	up to 36 months

Collaborators and Investigators

• Sponsor: Brno University Hospital
• Investigators: Principal Investigator: Jiří Žurek, M.D., Ph.D., Department of Anesthesia and Intensive Care, University Children´s Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: December 8, 2015
• First Submitted That Met QC Criteria: December 28, 2015
• First Posted (Estimate): December 31, 2015

Study Record Updates

• Last Update Posted (Estimate): January 1, 2016
• Last Update Submitted That Met QC Criteria: December 31, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Disease; Shock; Sepsis; Toxemia; Syndrome; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: KDAR 19 - 1