Presepsin to safely reduce antibiotics in preterm infants (PRESAFE): a randomized controlled trial with a concurrent observational study.

Presepsin to safely reduce antibiotics in preterm infants (PRESAFE): a randomized controlled trial with a concurrent observational study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Presepsin to safely reduce antibiotics in preterm infants (PRESAFE): a randomized controlled trial with a concurrent observational study. Charlotte M. Nusman, H. (Rob) Taal, Daniel C. Vijlbrief, Vincent Bekker, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7240890/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Feb, 2026 Read the published version in Trials → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Accurate and rapid diagnosis of early-onset neonatal sepsis (EOS) in preterm infants remains problematic due to lack of specific symptoms and diagnostic tools. Following the Dutch EOS guidelines, over 80% of infants born <32 weeks of gestation 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 and long term complications. The biomarker presepsin, also known as soluble CD14 subtype, may be used to reduce antibiotic prescription in preterm infants after birth. The objective of this study is to investigate whether adding a presepsin-guided decision to the guideline safely reduces antibiotic exposure directly after birth in preterm infants. Secondly, the diagnostic accuracy of presepsin for EOS will be evaluated. Methods: The PRESAFE trial is a multicentre, randomized controlled trial (RCT), including a concurrent observational study. Presepsin levels are determined from umbilical cord blood or during first regular blood draw in all infants born <32 weeks gestation. Infants who qualify for empirical antibiotics according to the Dutch EOS guideline are categorized as moderate or high risk for EOS based on prespecified high risk criteria. Infants not qualifying for empirical antibiotics are categorized as low risk. Preterm infants with a moderate risk for EOS are randomized 1:1 into an intervention arm and a comparator arm. In infants allocated to the intervention arm, empirical antibiotics will only be started above a prespecified presepsin level of ≥645pg/ml. In the comparator arm infants will be treated according to standard of care following the Dutch EOS guideline, equivalent to starting empirical antibiotics. The co-primary outcomes of the RCT are the incidence of culture-proven EOS (non-inferiority) and unnecessary antibiotics administration (superiority). The required sample size for the RCT is 900 patients. Infants with a high- or low-risk of EOS are excluded for randomization but included in a concurrent observational study, and treated according to the Dutch EOS guideline. The primary outcome of this part is diagnostic accuracy of presepsin. Discussion: The findings of the RCT will provide evidence for safe and effective reduction of administration of antibiotics for suspected EOS in infants born <32 weeks of gestation. The observational study will provide more insight in diagnostic accuracy of all infants born <32 weeks of gestation. Trial registration: ClinicalTrials.gov NCT06100614. First registered on October 25, 2023. Preterm infants early-onset sepsis antibiotics biomarker Full Text Cite Share Download PDF Status: Published Journal Publication published 27 Feb, 2026 Read the published version in Trials → Version 1 posted Editorial decision: Minor revision 14 Jan, 2026 Reviewers agreed at journal 02 Oct, 2025 Reviewers invited by journal 02 Oct, 2025 Editor assigned by journal 11 Aug, 2025 First submitted to journal 29 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7240890","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":523832325,"identity":"aac1d858-8df0-4c4c-a93e-04b85dfbf573","order_by":0,"name":"Charlotte M. 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Following the Dutch EOS guidelines, over 80% of infants born \u0026lt;32 weeks of gestation 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 and long term complications. The biomarker presepsin, also known as soluble CD14 subtype, may be used to reduce antibiotic prescription in preterm infants after birth. The objective of this study is to investigate whether adding a presepsin-guided decision to the guideline safely reduces antibiotic exposure directly after birth in preterm infants. Secondly, the diagnostic accuracy of presepsin for EOS will be evaluated.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods: The PRESAFE trial is a multicentre, randomized controlled trial (RCT), including a concurrent observational study. Presepsin levels are determined from umbilical cord blood or during first regular blood draw in all infants born \u0026lt;32 weeks gestation. Infants who qualify for empirical antibiotics according to the Dutch EOS guideline are categorized as moderate or high risk for EOS based on prespecified high risk criteria. Infants not qualifying for empirical antibiotics are categorized as low risk. Preterm infants with a moderate risk for EOS are randomized 1:1 into an intervention arm and a comparator arm. In infants allocated to the intervention arm, empirical antibiotics will only be started above a prespecified presepsin level of ≥645pg/ml. In the comparator arm infants will be treated according to standard of care following the Dutch EOS guideline, equivalent to starting empirical antibiotics. The co-primary outcomes of the RCT are the incidence of culture-proven EOS (non-inferiority) and unnecessary antibiotics administration (superiority). The required sample size for the RCT is 900 patients. Infants with a high- or low-risk of EOS are excluded for randomization but included in a concurrent observational study, and treated according to the Dutch EOS guideline. The primary outcome of this part is diagnostic accuracy of presepsin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDiscussion: The findings of the RCT will provide evidence for safe and effective reduction of administration of antibiotics for suspected EOS in infants born \u0026lt;32 weeks of gestation. The observational study will provide more insight in diagnostic accuracy of all infants born \u0026lt;32 weeks of gestation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTrial registration:\u0026nbsp;ClinicalTrials.gov NCT06100614. 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