To investigate whether addition of a presepsin-guided step to the Dutch EOS guideline safely reduces unnecessary empirical antibiotic exposure directly after birth in preterm infants born
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In all patients <32 weeks of gestation presepsin levels will be determined in
plasma preferably derived from umbilical cord blood. The co-primary outcomes of
the RCT are: 1) the incidence of a culture-proven EOS (non-inferiority) and 2)
unnecessary antibiotics administration (superiority). The primary outcome of
the observational part is the diagnostic accuracy of presepsin directly after
birth for EOS.
Secondary outcome
Secondary outcomes include: sepsis-related severity of illness, total number of
antibiotic days (started <72 hours after birth), incidence of the composite
outcome of necrotizing enterocolitis, late-onset sepsis, or death, incidence of
bronchopulmonary dysplasia, intraventricular haemorrhage and/or periventricular
leukomalacia, retinopathy of prematurity. We further will evaluate the
neurocognitive outcome and related health care costs.
Background summary
Accurate and rapid diagnosis of early-onset neonatal sepsis (EOS) remains
problematic in preterm infants mainly due to the non-specific signs and
symptoms, and lack of reliable, rapid diagnostic tools. Over 80% of preterm
infants are empirically started on antibiotics directly after birth, while the
actual incidence of EOS varies between 1-2%. Unnecessary antibiotic exposure
leads to severe short term and long term complications. Presepsin is a
promising biomarker for reducing antibiotic exposure in preterm infants as
concentrations increase rapidly after infection onset and it has a high
specificity for bacterial infections.
Study objective
To investigate whether addition of a presepsin-guided step to the Dutch EOS
guideline safely reduces unnecessary empirical antibiotic exposure directly
after birth in preterm infants born <32 weeks gestation at moderate risk of
EOS. Secondly, the diagnostic accuracy of presepsin for EOS will be evaluated.
Study design
Multicenter, parallel groups, superiority and non-inferiority randomized
clinical trial (RCT) with a concurrent observational cohort.
Intervention
Intervention: empirical antibiotics will be started when the presepsin level is
>645 pg/ml. Comparator: standard care according to the Dutch guideline.
Study burden and risks
Participation in the study involves no additional punctures in the patients, as
the biomarker blood sample will be drawn from the umbilical cord or during a
regular blood draw within the first 4 hours after birth. Patients at low or
high risk of EOS are excluded from the RCT to reduce the extra risk for
antibiotic exposure in the low risk group and to reduce the risk for missing
EOS cases in the high risk group. For the included patients (who are at
moderate risk of EOS, and clinical equipoise is suggested for antibiotic
treatment versus no treatment), the hypothetical risk of developing sepsis
while not receiving antibiotics is covered by choosing a cut-off value of
presepsin with 100% sensitivity. Furthermore, all patients will be closely
monitored in an intensive care setting allowing clinicians to perform a sepsis
evaluation and start antibiotic treatment in case of clinical deterioration
within the study period.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Infants born between 24 and 31+6 weeks gestation are eligible for enrollment.
Infants at high- or low-risk of early-onset sepsis will be excluded for
randomization and included in the observational part of the study. Infants with
moderate risk for EOS are randomized 1:1.
Exclusion criteria
Infants at low-risk or high-risk for EOS are not eligible for enrollment in the
randomization part of the trial.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT06100614 |
| CCMO | NL85180.018.24 |