Utility of Presepsin in Children Sepsis

Sepsis Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02643121
• Other study ID #: KDAR 19 - 1
• Status: Active, not recruiting
• Phase: N/A
• First received: December 8, 2015
• Last updated: December 31, 2015
• Start date: January 2014
• Est. completion date: January 2017

Study information

• Verified date: December 2015
• Source: Brno University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: Ethics Committee
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: January 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 1 Month to 216 Months

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Sepsis
• Sepsis Syndrome
• Systemic Inflammatory Response Syndrome
• Toxemia

Intervention

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

Locations

Country	Name	City	State
Czech Republic	Faculty Hospital Brno	Brno

Sponsors (1)

Lead Sponsor	Collaborator
Brno University Hospital

Country where clinical trial is conducted

Czech Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Primary	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	Yes
Secondary	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	Yes