Validation of Biomarkers Performance to Reduce Antibiotics overUse in newBorns With Suspected Clinical Signs of InfectionS (RUBIS)

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 related 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. This explains why 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.

A previous study (EMERAUDE) aimed to identify new biomarkers to early exclude the diagnosis of LOS, in order to limit antibiotic overuse. This study including 230 neonates revealed high performances of IL6, IL10, NGAL and combinations of PCT/IL10 and PTX3/NGAL.

The main objective of the present study will be to validate the performances of these biomarkers in another cohort. The secondary objectives will be to explore transcriptomic biomarkers and salivary biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Neonatal Late Onset Sepsis
• Intervention / Treatment: Diagnostic test: Newborns suspected of Infections

• Study Type: Observational
• Enrollment (Estimated): 358

Contacts and Locations

• Study Contact: Name: Marine BUTIN, Pr; Phone Number: +33 4 27 85 52 84; Email: marine.butin@chu-lyon.fr
• Study Contact Backup: Name: Sophie TROUILLET-ASSANT; Phone Number: +33 4 72 67 87 80; Email: sophie.trouillet-assant@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • neonatal Intensive care unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, France
    • Contact: Marine BUTIN, Pr; Phone Number: +33 4 27 85 52 84; Email: marine.butin@chu-lyon.fr
  • Grenoble, France, 38700
    • Recruiting
    • Hôpital Couple-Enfant - CHU Grenoble Alpes
    • Contact: LAYLI ALIN, MD; Phone Number: 00334 27 85 52 84; Email: lalin@chu-grenoble.fr
  • Nantes, France, 44300
    • Recruiting
    • Neonatal intensive care unit, Hôpital femme-maternité
    • Contact: FLAMANT Cyril, Pr; Phone Number: +33 2.40.08.34.83; Email: cyril.flamant@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newborns aged ≥ 7 days hospitalized in one of the 2 neonatal intensive care units (Nantes or Lyon) for whom an infection is suspected.

Description

Inclusion Criteria:

• Patient hospitalized in the NICU of one of the two recruiting centers at the time of inclusion
• Patients aged ≥ 7 days
• Patients weighted ≥ 500 g the day of blood sample
• patients with suggestive signs of LOS including at least one of the following:Fever > 38°C; tachycardia > 160bpm; capillary refill time > 3 seconds; grey and/or pale skin complexion; apnea/ bradycardia syndrome, bloating; vomiting; 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; or any other condition for which the clinician suspected an infection
• patients with a standard of care blood sampling, including at least a blood culture;

Exclusion Criteria:

• Patient treated with antibiotics for a bacteriologically confirmed infection at the time of sampling or within 48 hours prior to sampling
• Patient who underwent surgery within the previous 7 days
• Patients vaccinated within the previous 7 days
• Patient who received treatment with systemic corticosteroid therapy in the 48 hours prior to sampling
• Patient with severe combined immunodeficiency
• Opposition from parent(s)/guardian(s)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of late onset sepsis	The primary outcome measure will be determined by an independent adjudication committee that will classify the patients into the following categories : infection, non infected or undetermined. This committee will be blinded to the biomarkers of the study. It will be composed of two neonatologists and a pediatrician specialized in pediatric infectious diseases. The diagnostic performance of the biomarkers combination will be based on the adjudication committee classification (gold standard).	72 hours maximum after inclusion

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: biomarker; preterm neonates; NICU; antibiotic use; neonatal sepsis,; diagnostic,
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Neonatal Sepsis; Disease
• Other Study ID Numbers: 69HCL23_0633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No