Presepsin to Safely Reduce Antibiotics in Preterm Infants

NCT06100614 | Recruiting DMC

• 1 other identifier: 10140022210043
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 1

Brief Summary

In the Netherlands, more than 85% of the preterm infants born \<32 weeks gestational age get antibiotics directly after birth because of the risk of infection with a bacteria. However, only 1 in 70 of these preterm babies actually has a bacterial infection. The use of antibiotics after birth can lead to problems on short term (bowel infection, infection with a bacteria later on or death) or long term (asthma, allergy, obesity). The goal of the PRESAFE trial is to investigate whether addition of a biomarker (presepsin) to the Dutch early-onset neonatal sepsis (EOS) guideline safely reduces unnecessary empirical antibiotic exposure after birth in preterm infants born before 32 weeks gestational age. In this 874-subject multicenter, randomized clinical trial with a concurrent observational cohort, the hypothesis to be tested is that by adding presepsin to the national guideline the amount of unnecessary empirical antibiotic exposure after birth will be reduced with at least 30% without increase in infants with untreated sepsis. The study targets a population of clinical stable very preterm infants with risk factors for eary-onset neonatal sepsis. Antibiotic administration after birth is started to pre-emptively treat EOS. By adding a presepsin-guided step to the Dutch EOS guideline for those infants qualifying for antibiotic treatment, it is assumed that the rate of antibiotic administration can be reduced. However, it is imperative that this reduction in antibiotics is not outweighed by an increase in (culture proven) EOS. Therefore, the co-primary outcomes of the study are: 1) the incidence of culture-proven EOS (non-inferiority) and 2) unnecessary antibiotics prescription i.e. antibiotic administration for ≤ 3 days when started within the first 72 hours after birth (superiority). Secondary outcomes include sepsis-related severity of illness, total number of antibiotic days when started \< 72 hours after birth, and the composite outcome of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), or death until discharge from the initial hospital.

Conditions

Early-Onset Neonatal Sepsis

Keywords

preterm infants; antibiotics; presepsin

Outcome Measures

Primary Outcomes (2)

• the incidence of culture-proven early-onset sepsis

  non-inferiority

  72 hours after birth

• presence of unnecessary antibiotics prescription

  antibiotic administration for ≤3 days when started within the first 72 hours after birth (superiority)

  72 hours after birth

Secondary Outcomes (5)

• sepsis-associated severity of illness (nSOFA)

  from birth until discharge from initial hospital (up to 6 months)

• sepsis-associated severity of illness (meningitis)

  from birth until discharge from initial hospital (up to 6 months)

• sepsis-associated severity of illness (death)

  from birth until discharge from initial hospital (up to 6 months)

• total number of antibiotic days when started < 72 hours after birth

  from birth until discharge from initial hospital (up to 6 months)

• Presence of necrotizing enterocolitis and/or late-onset sepsis and/or death

  from birth until discharge from initial hospital (up to 6 months)

Study Arms (2)

Presepsin-guided therapy

EXPERIMENTAL

The decision to start empirical antibiotics in this group will be based on presepsin measurement within four hours after birth. When the presepsin value is above the cut-off value of 645 pg/ml, antibiotics will be ordered and administered within 4 hours of life and discontinued following the criteria of the Dutch EOS guideline. When the presepsin level is below the cut-off value of 645 pg/ml, the treating physician will not start antibiotic treatment. These infants will be closely observed for at least 72 hours. In case of deterioration of the clinical condition within this observation period, the clinician can decide to perform a sepsis evaluation and start with antibiotic treatment.

Diagnostic Test: Presepsin

Standard care

ACTIVE COMPARATOR

Standard care according to the Dutch EOS guideline. Presepsin will be determined with the treating physician blinded for the test result. In the Dutch EOS guideline maternal and neonatal risk factors for EOS are categorized as red flags or minor criteria. In the presence of 1 red flag or ≥ 2 minor criteria it is advised to perform a blood culture (= sepsis evaluation) and start empirical antibiotics for EOS suspicion. Antibiotic treatment will be advised to discontinue when blood culture turns back negative, reassuring the infants clinical condition with no other indicators of possible infection (e.g. CRP).

Diagnostic Test: Standard Care

Interventions

Presepsin DIAGNOSTIC_TEST

Umbilical cord blood or blood from the first routine venous puncture within four hours after birth will be used for presepsin determination. Presepsin measurement can be performed in 100 μl plasma with "PATHFAST™ Presepsin" which is a rapid chemiluminescent enzyme immunoassay (Mitsubishi Chemical Medience corporation, Tokyo, Japan) with results available within 15 minutes.

Presepsin-guided therapy

Standard Care DIAGNOSTIC_TEST

Standard care according to the Dutch EOS guideline

Standard care

Eligibility Criteria

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

You may qualify if:

• Infants born at a gestational age of 24+0 to 31 6/7 weeks
• Moderate risk of early-onset neonatal sepsis, i.e. infants who should be treated with empirical antibiotics based on the Dutch EOS guideline.

You may not qualify if:

• low risk of early-onset neonatal sepsis who do not have an indication for empirical antibiotics according to the Dutch EOS guideline;
• high risk of early-onset neonatal sepsis defined as:
• suspected or confirmed diagnosis of maternal sepsis;
• suspected or proven EOS in other infants (in case of multiple births) or infants born to mothers with previous infant with GBS disease/infection;
• unexplained respiratory insufficiency requiring invasive mechanical ventilation and FiO2\>0.40 or non-invasive ventilation with FiO2 \>0.60 at time of randomization;
• ongoing hemodynamic instability requiring inotrope medication or more than one 10 ml/kg fluid bolus at time of randomization;
• strong clinical concern for sepsis due to physical exam findings (i.e. minimal responsiveness, poor tone).

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Neonatal Sepsis

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 Officials

• Douwe Visser, MD PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Douwe Visser, MD PhD

CONTACT

+31205669111; d.h.visser@amsterdamumc.nl

Charlotte Nusman, MD PhD

CONTACT

+31205669111; c.m.nusman@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 15, 2023
• First Posted: October 25, 2023
• Study Start: September 23, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available after publication of the main article in peer-reviewed journal.

Locations

NL (1)