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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

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

Age range

7 day–14 day

Sex eligibility

All sexes

Study type

Observational

Primary location

neonatal Intensive care unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, France, Bron, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Newborns suspected of Infections

Diagnostic Test

This study will include NICU newborns of at least 7 days of life with suggestive signs of neonatal sepsis. The results will be extrapolated to this same population.

Primary outcomes

Diagnosis of late onset sepsis

Time frame: 72 hours maximum after inclusion

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).

Study contacts

Contact information is provided by the study sponsor or research team.

Marine BUTIN, Pr

CONTACT

[email protected]

+33 4 27 85 52 84

Sophie TROUILLET-ASSANT

CONTACT

[email protected]

+33 4 72 67 87 80

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: RUBIS

Important dates

Study start: 2023
Primary completion: 2027
Study completion: 2027
First posted: Sep 28, 2023
Registry last updated: Sep 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed