NCT05274776

Safely Reduce Newborn Antibiotic Exposure With the Early-onset Sepsis Calculator: a Cluster Randomized Study (EOS Calculator RCT)

Status unknown NA Last updated 31 January 2024

What this trial tests

NA trial testing EOS calculator in Early-Onset Sepsis, Neonatal in 1,830 participants. Status unknown.

Timeline

12 April 2022

Primary endpoint
1 April 2024

1 October 2024

Quick facts

Lead sponsor	prof. dr. Frans B. Plötz
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	1,830
Start date	12 April 2022
Primary completion	1 April 2024
Estimated completion	1 October 2024
Sites	10 locations across Netherlands

Drugs / interventions tested

• EOS calculator

Conditions studied

• Early-Onset Sepsis, Neonatal — all drugs for Early-Onset Sepsis, Neonatal →
• EOS — all drugs for EOS →

Sponsor

prof. dr. Frans B. Plötz

Who can join

Under 24 Hours, any sex, with Early-Onset Sepsis, Neonatal or EOS. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Co-primary superiority outcome: antibiotic therapy started within 24 hours after birth
  Time frame: 0-24 hours after birth
  The proportion of patients that started antibiotic therapy for suspected and, or proven EOS in the first 24 hours after birth.
• First co-primary non-inferiority outcome (safety): proportion of patients with respiratory support
  Time frame: 0-14 days after birth
  A composite non-inferiority outcome regarding the presence of one or more of the following four predefined safety criteria, namely 1) the need for any respiratory support, and/or 2) the need for an intravascular fluid bolus for hemodynamic instability due to sepsis, and/or 3) referral to a Neonatal Intensive Care Unit (NICU) for sepsis treatment, and/or 4) proven EOS. \- Respiratory support is de
• Second co-primary non-inferiority outcome (safety): proportion of patients with hemodynamic support
  Time frame: 0-14 days after birth
  \- Intravascular fluid bolus is defined as the intravenous administration of a fluid bolus of 10ml/kg within 15-30 minutes. It is the first step in the treatment of hemodynamically unstable newborns due to sepsis.
• Third co-primary non-inferiority outcome (safety): proportion of patients referred to a NICU for sepsis treatment
  Time frame: 0-14 days after birth
• Fourth co-primary non-inferiority outcome (safety): proportion of patients with proven EOS
  Time frame: 0-14 days after birth
  \- Proven EOS is defined as a blood or cerebrospinal fluid (CSF) culture obtained within 72 hours after birth growing a pathogenic bacterial species.

Sponsor's own description

Newborns are at risk for early-onset sepsis (EOS), which occurs within 72 hours after birth. The incidence of proven EOS is 0.5-2.0 per 1000 live births. The annual birth rate in the Netherlands is around 170.000, consequently the number of EOS cases varies between 85 to 340. However, about 5%, thus 8500, of late preterm and term newborns receive empiric antibiotic therapy in compliance with the current Dutch guideline. An alternative is the CE certified EOS calculator application, which calculates an individual EOS risk with treatment advice. In this prospective cluster-randomized multicenter trial the current Dutch guideline will be compared with the EOS calculator in newborns at risk for EOS.

The primary objectives of this study are:

1. To investigate whether the use of the EOS calculator reduces antibiotic exposure in newborns with suspected EOS in the first 24 hours after birth.
2. To investigate the presence of one or more of the following four predefined safety criteria, namely 1) the need for any respiratory support, and/or 2) the need for an intravascular fluid bolus for hemodynamic instability due to sepsis, and/or 3) referral to a Neonatal Intensive Care Unit for sepsis treatment, and/or 4) proven EOS.

Secondary objectives of the study are:

1. To investigate if the use of the EOS calculator decreases the total duration of antibiotic therapy in newborns with suspected EOS.
2. To investigate if the use of the EOS calculator decreases the percentage of antibiotic therapy started for suspected and, or proven EOS if symptoms started between 24-72 hours after birth.
3. To study the impact of (suspected) EOS on parents/guardians.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Evaluating safety and effectiveness of the early-onset sepsis calculator to reduce antibiotic exposure in Dutch at-risk newborns: a protocol for a cluster randomised controlled trial.
   van der Weijden BM, van der Weide MC, Plötz FB, Achten NB. · · 2023 · cited 7× · PMID 36787971 · DOI 10.1136/bmjopen-2022-069253
2. Safety and effectiveness of the early-onset sepsis calculator to reduce antibiotic exposure in at-risk newborns: a cluster-randomised controlled trial.
   van der Weijden BM, Janssen SWCM, van der Weide MC, Cornelisse-van Vugt RJPM, et al · · 2025 · PMID 40831464 · DOI 10.1016/j.eclinm.2025.103419