Interest of the Presepsin Assay as a Biomarker of Bacterial Infection, in the Management of Newborns and Infants Under 3 Months of Age Admitted for Fever in Pediatric Emergency Service (Presepsin) (presepsin)

Interest of the Presepsin Assay as a Biomarker of Bacterial Infection, in the Management of Newborns and Infants Under 3 Months of Age Admitted for Fever in Pediatric Emergency Service

The purpose of this study is to validate presepsin as a biological marker for identifying bacterial fever among febrile syndromes of infants under three months of age. Clearly, our goal is to determine if this marker can help us distinguish a viral infection from a bacterial infection. Indeed, presepsin would be specific for bacterial infection, and rise earlier in the blood during infection than biological markers currently used. Such validation could improve the precocity of the therapeutic management by a better targeted antibiotic therapy, and the limitation of invasive complementary examinations (lumbar puncture), in infants for whom the fear of a bacterial infection leads to examinations and systematic treatments.

Study Overview

• Status: Terminated
• Conditions: Fever; Newborn Sepsis
• Intervention / Treatment: Diagnostic test: Prespesin assay on PATHFAST analyser

Detailed Description

An exploratory proof of concept that evaluates an innovative and minimally invasive diagnostic technique, with brief, monocentric longitudinal follow-up, this study aims to validate presepsin as a biomarker for identifying bacterial fever among febrile syndromes of infants under three months of age. Presepsin is thought to be specific for sepsis, and would rise earlier in the blood during sepsis than biomarkers currently used. Such validation could improve the precocity of the therapeutic management by a better targeted antibiotic therapy, and the limitation of invasive complementary examinations (lumbar puncture), in infants for whom the fear of a bacterial infection leads to examinations and systematic treatments.

To do this, we will study the discriminative power (bacterial or viral, verified, a posteriori, by the results of microbiological examinations such as blood cultures, cytobacteriology of urine, lumbar puncture, virological or bacteriological samples of stool and nasopharynx) and prognosis (comparison of initial signs of clinical severity and presepsin levels, length of hospitalization and hospitalization unit) of presepsin by comparing its blood levels to the usual biological markers (CRP, PCT, leukocytes, neutrophils, lymphocytes) in children less than 3 months old with fever. It will also be compared, a posteriori, the rate of presepsin between the group of children treated with antibiotics and the group of untreated children to verify that the rate of presepsin is predictive of the initiation of antibiotic treatment.

If in this study the superiority of presepsin is confirmed, it will also be evaluated, by a medico-economic study, the effect of a decision of care based on the interpretation of the blood presepsin level on downstream health costs and on the speed of care of children under 3 months with fever presenting to the emergency department by the commissioning of a delocalized analyzer. This device is, for the moment, available only in the laboratory.

The study plans to include 160 children under 3 months admitted to pediatric emergencies or pediatric resuscitation at Estaing Hospital in Clermont-Ferrand.

Participation in the study will not require additional venipuncture given the very small amount of blood sufficient for the presepsin assay. The diagnosis of the child will not be made according to the presepsin test, but according to the standard criteria, and its management will not be modified by his participation in the study. Thus, the study presents neither benefit nor risk for the participants.

• Study Type: Observational
• Enrollment (Actual): 31

Contacts and Locations

Study Locations

• France
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63003
      • CHU de Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children under 3 months old with fever, a rectal temperature greater than or equal to 38 ° C, presenting at the pediatric emergency of the Estaing Hospital or directly in pediatric intensive care unit of the Estaing Hospital.

Description

Inclusion Criteria:

• Children under 3 months old with fever, a rectal temperature greater than or equal to 38 ° C, presenting at the pediatric emergency of the Estaing Hospital or directly in pediatric intensive care unit of the Estaing Hospital.
• Coverage by a social security scheme

Exclusion Criteria:

• Failure to perform a blood test
• Children who received antibiotics before admission.
• Refusal of participation by the legal representatives of the child
• Concomitant participation of the child in a therapeutic trial or other clinical study that may influence the results of this research

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bacterial group; Newborns or infants less dans 3 months old with fever and positive bacterial sample.	Diagnostic test: Prespesin assay on PATHFAST analyser; Collection of parental non-opposition by the doctor taking care of the child. Addition of an additional 500μl tube to the usual blood sampling as part of the protocol for the management of children under 3 months of age with fever. This blood test contains CRP, PCT, NFS, Hemoculture. There is no additional venipuncture. This blood sample is taken by the nurse after parental non-opposition. Transfer of the sample to the laboratory. In the laboratory, centrifugation of the sample, taking the plasma alone which will be frozen. Delayed assay of presepsin, in series, after thawing of samples. Collection of data and analyzes by the principal investigator in collaboration with the statistician methodologist. The immunoassay of presepsin with PATHFAST is based on chemiluminescence.
Viral group; Newborns or infants less dans 3 months old with fever and positive viral sample.	Diagnostic test: Prespesin assay on PATHFAST analyser; Collection of parental non-opposition by the doctor taking care of the child. Addition of an additional 500μl tube to the usual blood sampling as part of the protocol for the management of children under 3 months of age with fever. This blood test contains CRP, PCT, NFS, Hemoculture. There is no additional venipuncture. This blood sample is taken by the nurse after parental non-opposition. Transfer of the sample to the laboratory. In the laboratory, centrifugation of the sample, taking the plasma alone which will be frozen. Delayed assay of presepsin, in series, after thawing of samples. Collection of data and analyzes by the principal investigator in collaboration with the statistician methodologist. The immunoassay of presepsin with PATHFAST is based on chemiluminescence.
Negatives Microbiological samples; Newborns or infants less dans 3 months old with fever and negatives microbiological samples.	Diagnostic test: Prespesin assay on PATHFAST analyser; Collection of parental non-opposition by the doctor taking care of the child. Addition of an additional 500μl tube to the usual blood sampling as part of the protocol for the management of children under 3 months of age with fever. This blood test contains CRP, PCT, NFS, Hemoculture. There is no additional venipuncture. This blood sample is taken by the nurse after parental non-opposition. Transfer of the sample to the laboratory. In the laboratory, centrifugation of the sample, taking the plasma alone which will be frozen. Delayed assay of presepsin, in series, after thawing of samples. Collection of data and analyzes by the principal investigator in collaboration with the statistician methodologist. The immunoassay of presepsin with PATHFAST is based on chemiluminescence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Presepsin	Presepsin rate measured in picograms / milliliters, using the PATHFAST analyzer.	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of C-reactive protein	CRP level in milligrams / Liter	Day 0
Measure of Procalcitonin	PCT rate in microgram/ Liter	Day 0
Length of hospital stay	comparison between the presepsin rate and the duration of hospitalization to verify the prognostic power of presepsin (Day)	through study completion, an average of one week
Total costs	Total costs represents cost of presepsin assay, cost of CRP and PCT assay, average cost per day of a hospital stay of a febrile child less than 3 months depending on the unit, laboratory personal cost (in euros). This allows the evaluation, by a medico-economic study, of the effect of a decision of care based on the interpretation of the blood pressepsin level on the downstream health costs and on the speed of taking care of patients children under 3 months with fever presenting to the emergency department by setting up a delocalized analyzer.	through study completion, an average of one week

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Mitsubishi Chemical Europe
• Investigators: Principal Investigator: POIRIER Véronique, Chu Estaing

Publications and helpful links

General Publications

• Pugni L, Pietrasanta C, Milani S, Vener C, Ronchi A, Falbo M, Arghittu M, Mosca F. Presepsin (Soluble CD14 Subtype): Reference Ranges of a New Sepsis Marker in Term and Preterm Neonates. PLoS One. 2015 Dec 31;10(12):e0146020. doi: 10.1371/journal.pone.0146020. eCollection 2015.
• Okamura Y, Yokoi H. Development of a point-of-care assay system for measurement of presepsin (sCD14-ST). Clin Chim Acta. 2011 Nov 20;412(23-24):2157-61. doi: 10.1016/j.cca.2011.07.024. Epub 2011 Aug 3.
• Chenevier-Gobeaux C, Bardet V, Poupet H, Poyart C, Borderie D, Claessens YE. Presepsin (sCD14-ST) secretion and kinetics by peripheral blood mononuclear cells and monocytic THP-1 cell line. Ann Biol Clin (Paris). 2016 Jan-Feb;74(1):93-7. doi: 10.1684/abc.2015.1112.
• Pizzolato E, Ulla M, Galluzzo C, Lucchiari M, Manetta T, Lupia E, Mengozzi G, Battista S. Role of presepsin for the evaluation of sepsis in the emergency department. Clin Chem Lab Med. 2014 Oct;52(10):1395-400. doi: 10.1515/cclm-2014-0199.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Actual): July 29, 2020
• Study Completion (Actual): July 29, 2020

Study Registration Dates

• First Submitted: August 26, 2019
• First Submitted That Met QC Criteria: August 30, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: biomarker; fever; newborns; presepsin; infants under 3 months of age; paediatric emergency
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Bacterial Infections and Mycoses; Body Temperature Changes; Emergencies; Fever; Bacterial Infections
• Other Study ID Numbers: RNI 2019 POIRIER; 2019-A00704-53 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No