Utility of Presepsin in Children Sepsis

NCT ID: NCT02643121

Last Updated: 2016-01-01

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2017-01-31

Brief 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).

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.

Conditions

Sepsis Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

therapy sepsis

Intervention Type: OTHER

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.

No interventions assigned to this group

Interventions

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• 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

Control

• no informed consent

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 216 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brno University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jiří Žurek

M.D., Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jiří Žurek, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Anesthesia and Intensive Care, University Children´s Hospital

Locations

Faculty Hospital Brno

Brno, , Czechia

Countries

Czechia

Other Identifiers

KDAR 19 - 1

Identifier Type: -

Identifier Source: org_study_id