Presepsin to Safely Reduce Antibiotics in Preterm Infants

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

Interventions

DIAGNOSTIC_TEST

Presepsin

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.

DIAGNOSTIC_TEST

Standard Care

Standard care according to the Dutch EOS guideline

Sponsors & Collaborators

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

  lead OTHER

Principal Investigators

• Douwe Visser, MD PhD · Amsterdam UMC

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-09-23

Primary Completion

2027-01-01

Completion

2027-01-01

Countries

• Netherlands

Study Locations