Neutrophil Extracellular Traps and Neonatal (PV4991) & Pediatric Sepsis (PV5063)

This study is designed to assess the role of neutrophil extracellular traps (NETs) in neonatal and pediatric sepsis as well as to evaluate markers of NETs formation as early predictors of neonatal and pediatric sepsis.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Other: Markers of NET formation

Detailed Description

Severe infection resulting in sepsis is recognized as a leading cause of morbidity and mortality worldwide (Stehr and Reinhart, 2013). The incidence of sepsis in developed nations has been increasing while overall mortality is decreasing, but still remains around 30% (Mayr et al., 2014). Moreover, morbidity in survivors is often functionally devastating, and may include neurological impairment, chronic organ dysfunction, increased days admitted to hospital, and high rates of mortality postdischarge (Prescott et al., 2014). Emotional, social, and financial costs to individuals and health care systems are immense (Brun-Buisson et al., 2003).

Neutrophils are the first line of innate immune defense against infectious agents. In addition, neutrophils' ability to eliminate pathogens by phagocytosis and/or degranulation, it has recently been demonstrated that neutrophils can bind to and kill a wide range of microorganisms by forming neutrophil extracellular traps (NETs) (Brinkmann et al., 2004). This novel mechanism consists of the release of web-like structures of DNA decorated with histones and antimicrobial proteins, known as NETs. Microbes are immobilized in these traps, which contain a lethal concentration of antimicrobial agents killing a broad range of microorganisms, including gram-negative and gram-positive bacteria, fungi, viruses, and protozoa (Brinkmann et al., 2004, Fuchs et al., 2010, Camicia et al., 2014).

The role of NETs in pediatric infection is not well understood. We hypnotize that children are capable of forming NETs and that NETosis plays an important role in pediatric sepsis. This study is designed to assess the role of neutrophil extracellular traps (NETs) in neonatal and pediatric sepsis as well as to evaluate markers of NETs formation as early predictors of neonatal and pediatric sepsis.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • University Medical Center Hamburg-Eppendorf
    • Contact: Michael C Boettcher, M.D.; Phone Number: +4915222815153; Email: m.boettcher@uke.de
  • Hamburg, Germany, 22763
    • Recruiting
    • Altona Children's Hospital
    • Contact: Michael Boettcher, M.D.; Phone Number: +4015222815153; Email: m.boettcher@uke.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All children with suspected sepsis

Description

Inclusion Criteria:

1. Signed informed consent by the parent or guardian of the patient
2. Chronological age below 90 days (= neonatal branch) or below 18 years (pediatric branch)
3. Suspicion of sepsis infection

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
Actual Sepsis; For infants below 44 weeks inclusive of corrected age clinical sepsis is defined, according to the Expert Meeting on Neonatal and Pediatric Sepsis (Report on the Expert Meeting on Neonatal and Pediatric Sepsis - 8 June 2010, EMA London). Confirmed sepsis is defined as positive culture for pathogens in a sample from a normally sterile site and at least one laboratory sign or clinical sign (not shown) For children above 44 weeks corrected age clinical sepsis is defined according to the Goldstein criteria (Goldstein et al, 2005). Confirmed sepsis: positive culture for pathogens in a sample from a normally sterile site and at least one laboratory sign or clinical sign (not shown)	Other: Markers of NET formation; i.e. Plasma DNA, Histone, MPO, DNase; Other Names: Typical biomarkers of NETosis
Suspected Sepsis; None of the above.	Other: Markers of NET formation; i.e. Plasma DNA, Histone, MPO, DNase; Other Names: Typical biomarkers of NETosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Extracellular Traps	Neutrophil Extracellular Traps are measured by serum markers	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sepsis	Sepsis is defined according to the Goldstein criteria 2015.	2 weeks

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: October 1, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): June 23, 2017
• Last Update Submitted That Met QC Criteria: June 22, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: PV4991 & PV5063