Evaluation of bioMarkErs to Reduce Antibiotics Use in hospitalizeD nEonates

NCT03299751 | Completed

• 1 other identifier: 69HCL17_0492
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 2

Brief Summary

Late-onset neonatal sepsis (LOS), occurring in newborn of at least 7 days of life, is frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe (mortality, neurologic and respiratory impairments). Despite its high prevalence, a reliable diagnostic remains difficult. Currently, nonspecific clinical signs that might be linked to other neonatal conditions, such as prematurity and birth defects are used to determine the diagnosis of LOS. Laboratory results of biological markers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) are often delayed in comparison with LOS onset. Blood culture results are too late and lack sensitivity. Excessive antibiotic use is observed in a large proportion of NICU hospitalized newborns. This results in an increased antibiotic resistance, microbiota modification, neonatal complications (pulmonary, ophthalmologic and neurologic) and mortality. The primary objective is to identify, on a cohort of 250 patients, the optimal biomarker combination with good diagnostic performance (i.e. with maximal Area Under the ROC Curve) to early exclude a LOS diagnostic in newborns of at least 7 days of life with suggestive signs. This identification will be carried out, as a secondary objective, with a sub-group of pre-term neonates whose birth weight is less than 1500 grams. The diagnostic value of the clinical signs that are suggestive of LOS will also be determined (sensitivity, specificity, negative and positive predictive values). Once identified, the biomarker combination is expected to reduce unjustified antibiotic use.

Conditions

Late-Onset Neonatal Sepsis

Keywords

neonatal sepsis; biomarker combination; diagnostic; antibiotic use; newborn; preterm neonates; NICU

Outcome Measures

Primary Outcomes (1)

• LOS diagnosis in NICU newborns of at least 7 days of life with suggestive clinical signs, confirmed by adjudication committee

  The primary outcome measure will be determined by an independent adjudication committee that will classify the patients into the following categories: infected, not infected or unclassified patients. This committee will be blinded to the biomarkers that will be used to identify a combination with the best negative predictive value. It will be composed of two neonatologists and a pediatrician specialized in the child infectious diseases. The diagnostic performance of the biomarkers combination will be based on the adjudication committee

  hour 48

Secondary Outcomes (1)

• LOS diagnosis in NICU preterm neonates, whose weight at birth is less than 1500 grams, of at least 7 days of life, with suggestive clinical signs, confirmed by adjudication committee.

  Hour 48

Study Arms (1)

NICU newborns of at least 7 days of life with suggestive signs

EXPERIMENTAL

Biological: Diagnostic performances of biomarkers combination

Interventions

Diagnostic performances of biomarkers combination BIOLOGICAL

A blood sample of 400µL will be drawn at inclusion, when neonatal sepsis is suspected, at the same time of a venipuncture prescribed for standard care. The dosage of 11 biomarkers will be performed in a central laboratory. The adjudication committee composed with 3 neonatalogists will classify patients in 3 groups (infected, not infected or unclassified patients), based on their clinical and biological data obtained, through the standard of care practice, during the 48 hours following inclusion. The adjudication committee will be blinded to the biomarkers results. The adjudication committee composed with 3 neonatalogists will classify patients in 3 groups (infected, not infected or unclassified patientsconfirmed infection, refuted infection), based on their clinical and biological data obtained, through the standard of care practice, during the 48 hours following inclusion. The adjudication committee will be blinded to the biomarkers results.

NICU newborns of at least 7 days of life with suggestive signs

Eligibility Criteria

• Age: 7 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• patients hospitalized in NICU;
• patients with suggestive signs of LOS including at least one of the following:
• o Fever \> 38°C; tachycardia \> 160bpm160 bpm; capillary refill time \> 3 seconds; grey and/or pale skin complexion; apnea/ bradycardia syndrome,; bloating; rectal bleeding; hypotonia; lethargy; seizures without other obvious cause; increased ventilatory support and/or increased FiO2; cutaneous rash; inflammation at the needle-puncture site of the central venous catheter;
• patients with a standard of care blood sampling, including at least a blood culture;
• consent form signed by at least one parent/ legal representative.

You may not qualify if:

• patients treated with antibiotics for a bacteriologically confirmed infection at the moment of/ or 48 hours before blood sampling

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Hospices Civils de Lyon

Bron, 69500, France

Location

CHU de Nantes

Nantes, France

Location

Related Publications (1)

• Pons S, Trouillet-Assant S, Subtil F, Abbas-Chorfa F, Cornaton E, Berthiot A, Galletti S, Plat A, Rapin S, Trapes L, Generenaz L, Brengel-Pesce K, Callies A, Plaisant F, Claris O, Portefaix A, Flamant C, Butin M. Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study. Biomedicines. 2023 Jun 13;11(6):1703. doi: 10.3390/biomedicines11061703.

  PMID: 37371798 BACKGROUND

MeSH Terms

Conditions

Neonatal Sepsis; Disease

Condition Hierarchy (Ancestors)

Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 3, 2017
• Study Start: November 22, 2017
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)