Safely Reduce Newborn Antibiotic Exposure With the Early-onset Sepsis Calculator
NCT ID: NCT05274776
Last Updated: 2024-02-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
1830 participants
INTERVENTIONAL
2022-04-12
2024-10-31
Brief Summary
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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.
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Detailed Description
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The current standard of care in the Netherlands is the Dutch Society of the Nederlands (NVK) guideline "Prevention and treatment of early-onset neonatal infections", which is an adaptation of the 2012 version of the National Institute for Health and Care Excellence (NICE) guideline "Antibiotics for early-onset neonatal infection: antibiotics for the prevention and treatment of early-onset neonatal infection". The NVK guideline uses risk factors and symptoms to categorically indicate which newborns need antibiotic therapy. Evaluating its use in 9 Dutch hospitals, limited adherence was found, especially when antibiotics were recommended by the guideline but withheld by the clinicians. This limited adherence indicates that it is desirable to amend the current guideline or to investigate the use of an alternative method.
A new method for determining which newborns need antibiotic therapy is the "EOS calculator". Developed in the United States, this method uses a combination of detailed information about 5 maternal risk factors and the presence of clinical neonatal symptoms to calculate an individual EOS risk and treatment advice.
For the Dutch situation, equipoise between the current NVK guideline and the EOS calculator can be established given balance of risk for both over- and undertreatment of EOS for both strategies. A large body of evidence now supports the safety of the EOS calculator approach, but validation outside of the North-American setting is limited, especially for safety outcomes.
A prospective cluster-randomized Dutch validation study of the EOS calculator is needed before implementation because of the following reasons:
1. Multicenter validation of actual EOS calculator use has not been performed in the Netherlands.
2. To date, no randomized prospective study of EOS calculator use with safety as an outcome measure has been performed. Specifically, there are no studies that take into account the potential effects of a treatment delay due to EOS calculator use. This especially holds true for cases that are clinically suspect for EOS, but not culture-confirmed.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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NVK Guidelines
The NVK guidelines use 8 maternal and 15 neonatal risk factors, each categorized as either red flag or non-red flag. These criteria guide clinicians on the management in case of suspected EOS. Briefly, antibiotic treatment is recommended if at least one red flag and, or, two or more non-red flags are present. An observation period of at least 12 hours is recommended if one non-red flag is present. Antibiotics are recommended when an infection is suspected during this observation. Newborns without EOS risk factors, with a good clinical condition, and a gestational age of more than 36 weeks will be discharged. If the guidelines recommend an observation period, the newborn with a good clinical condition is discharged after repeating physical examination. In case antibiotic treatment is started, discharge depends on the duration of treatment and the clinical course. At discharge, parents are instructed to call the hospital in case of signs of infection within the first 14 days of life.
No interventions assigned to this group
EOS Calculator
Using the EOS calculator application between 0-24 hours after birth, maternal EOS risk factors combined with the physical examination of the newborn are used to assign a risk category and accompanying clinical recommendation based on estimated EOS incidence for each newborn at-risk for an infection. The EOS calculator results are used to guide clinical management on performing either a diagnostic work-up and start of antibiotics for (suspected) EOS, or a conservative approach with routine controls of vital parameters every 3 hours. In case of routine controls, re-evaluation of physical appearance by a pediatric resident or pediatrician will take place within 24 hours postpartum. Newborns will be observed for at least 24 hours. In case antibiotics are started, the need for further treatment is depending on blood culture results, infection parameters, and clinical condition of the newborn. Discontinuation of antibiotics and discharge is at the discretion of the treating physician.
EOS calculator
For this study the EOS calculator was developed as a mobile application (by everywhereIM), including CE marking. It is concerned a medical device for health care professionals.
Interventions
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EOS calculator
For this study the EOS calculator was developed as a mobile application (by everywhereIM), including CE marking. It is concerned a medical device for health care professionals.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* age between 0-24 hours;
* at least one EOS risk factor or clinical sign of infection (suspected of EOS) present within the first 24 hours of life;
* parental/guardian consent.
Exclusion Criteria
* language barrier (lack of effective communication or whenever it hinders understanding).
24 Hours
ALL
No
Sponsors
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Dutch Society of Pediatrics
UNKNOWN
Zorgevaluatie Nederland
UNKNOWN
Care4Neo
UNKNOWN
everywhereIM
UNKNOWN
prof. dr. Frans B. Plötz
OTHER
Responsible Party
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prof. dr. Frans B. Plötz
Professor of Pediatric Health Care Evaluation
Principal Investigators
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Frans B. Plötz, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Amsterdam UMC, Tergooi Ziekenhuizen
Niek B. Achten, MD, PhD
Role: STUDY_DIRECTOR
Erasmus Medical Center
Bo M. van der Weijden, MD
Role: STUDY_DIRECTOR
Amsterdam UMC, Tergooi Ziekenhuizen
Locations
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Northwest Clinics
Alkmaar, , Netherlands
FlevoHospital
Almere Stad, , Netherlands
Amstelland Hospital
Amstelveen, , Netherlands
OLVG
Amsterdam, , Netherlands
Martini Hospital
Groningen, , Netherlands
Spaarne Hospital
Haarlem, , Netherlands
Dijklander Hospital
Hoorn, , Netherlands
Canisius-Wilhelmina Hospital
Nijmegen, , Netherlands
Máxima Medical Center
Veldhoven, , Netherlands
Zaans Medical Centre
Zaandam, , Netherlands
Countries
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Central Contacts
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References
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Sagori Mukhopadhyay, Karen M. Puopolo; Neonatal Early-Onset Sepsis: Epidemiology and Risk Assessment. Neoreviews April 2015; 16 (4): e221-e230.
Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014 Jan;27(1):21-47. doi: 10.1128/CMR.00031-13.
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NVOG (Nederlandse Vereniging voor Obstetrie en Gynaecologie), NVK (Nederlandse Vereniging Kindergeneeskunde). Preventie en behandeling van early-onset neonatale infecties (Adaptatie van de NICE-richtlijn). 2017 p. 1-94.
Neonatal infection: antibiotics for prevention and treatment. London: National Institute for Health and Care Excellence (NICE); 2024 Mar 19. Available from http://www.ncbi.nlm.nih.gov/books/NBK571222/
van der Weijden BM, Achten NB, Bekhof J, Evers EE, Berk M, Kamps AWA, Rijpert M, Ten Tusscher GW, van Houten MA, Plotz FB. Multicentre study found that adherence to national antibiotic recommendations for neonatal early-onset sepsis was low. Acta Paediatr. 2021 Mar;110(3):791-798. doi: 10.1111/apa.15488. Epub 2020 Aug 10.
Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, Newman TB, Zupancic J, Lieberman E, Draper D. Stratification of risk of early-onset sepsis in newborns >/= 34 weeks' gestation. Pediatrics. 2014 Jan;133(1):30-6. doi: 10.1542/peds.2013-1689. Epub 2013 Dec 23.
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Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, Kipnis P, Escobar GJ. A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis. JAMA Pediatr. 2017 Apr 1;171(4):365-371. doi: 10.1001/jamapediatrics.2016.4678.
Achten NB, Klingenberg C, Benitz WE, Stocker M, Schlapbach LJ, Giannoni E, Bokelaar R, Driessen GJA, Brodin P, Uthaya S, van Rossum AMC, Plotz FB. Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis. JAMA Pediatr. 2019 Nov 1;173(11):1032-1040. doi: 10.1001/jamapediatrics.2019.2825.
Achten NB, Dorigo-Zetsma JW, van der Linden PD, van Brakel M, Plotz FB. Sepsis calculator implementation reduces empiric antibiotics for suspected early-onset sepsis. Eur J Pediatr. 2018 May;177(5):741-746. doi: 10.1007/s00431-018-3113-2. Epub 2018 Feb 18.
van der Weijden BM, Achten NB, Bekhof J, Evers EE, van Dongen O, Rijpert M, Kamps AWA, Ten Tusscher GW, van Houten MA, Plotz FB. Neonatal early-onset sepsis calculator recommended significantly less empiric antibiotic treatment than national guidelines. Acta Paediatr. 2020 Dec;109(12):2549-2551. doi: 10.1111/apa.15391. Epub 2020 Jun 17. No abstract available.
Achten NB, Klingenberg C, Plotz FB. Neonatal Early-Onset Sepsis Calculator and Antibiotic Therapy-Reply. JAMA Pediatr. 2020 May 1;174(5):508-509. doi: 10.1001/jamapediatrics.2019.6269. No abstract available.
Kerste M, Corver J, Sonnevelt MC, van Brakel M, van der Linden PD, M Braams-Lisman BA, Plotz FB. Application of sepsis calculator in newborns with suspected infection. J Matern Fetal Neonatal Med. 2016 Dec;29(23):3860-5. doi: 10.3109/14767058.2016.1149563. Epub 2016 Mar 7.
Achten, N. B., Zonneveld, R., Tromp, E., & Plotz, F. B. (2017). Association between sepsis calculator and infection parameters for newborns with suspected early onset sepsis. Journal of clinical neonatology, 6(3), 159-162.
Achten NB, Visser DH, Tromp E, Groot W, van Goudoever JB, Plotz FB. Early onset sepsis calculator implementation is associated with reduced healthcare utilization and financial costs in late preterm and term newborns. Eur J Pediatr. 2020 May;179(5):727-734. doi: 10.1007/s00431-019-03510-9. Epub 2020 Jan 2.
Achten NB, Dorigo-Zetsma JW, van Rossum AMC, Oostenbrink R, Plotz FB. Risk-based maternal group B Streptococcus screening strategy is compatible with the implementation of neonatal early-onset sepsis calculator. Clin Exp Pediatr. 2020 Oct;63(10):406-410. doi: 10.3345/cep.2020.00094. Epub 2020 Apr 16.
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Benitz WE, Achten NB. Technical assessment of the neonatal early-onset sepsis risk calculator. Lancet Infect Dis. 2021 May;21(5):e134-e140. doi: 10.1016/S1473-3099(20)30490-4. Epub 2020 Oct 29.
Achten NB, Plotz FB, Klingenberg C, Stocker M, Bokelaar R, Bijlsma M, Giannoni E, van Rossum AMC, Benitz WE. Stratification of Culture-Proven Early-Onset Sepsis Cases by the Neonatal Early-Onset Sepsis Calculator: An Individual Patient Data Meta-Analysis. J Pediatr. 2021 Jul;234:77-84.e8. doi: 10.1016/j.jpeds.2021.01.065. Epub 2021 Feb 3.
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van der Weijden BM, Janssen SWCM, van der Weide MC, Cornelisse-van Vugt RJPM, Ten Tusscher GW, Lutterman CAM, Kamps AWA, Lorente Flores CM, Hol J, van Laerhoven H, Rijpert M, Oeij NA, Schiering IAM, Obermann-Borst SA, Visser DH, van Leeuwen LM, Kornelisse RF, van Rossum AMC, Bijlsma MW, Plotz FB, Achten NB. Safety and effectiveness of the early-onset sepsis calculator to reduce antibiotic exposure in at-risk newborns: a cluster-randomised controlled trial. EClinicalMedicine. 2025 Aug 12;87:103419. doi: 10.1016/j.eclinm.2025.103419. eCollection 2025 Sep.
van der Weijden BM, van der Weide MC, Plotz FB, Achten NB. 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. BMJ Open. 2023 Feb 14;13(2):e069253. doi: 10.1136/bmjopen-2022-069253.
Related Links
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Webpage of Zorgevaluatie Nederland, where everybody can find all study-related information, documents and progress.
Other Identifiers
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NL78203.018.21
Identifier Type: -
Identifier Source: org_study_id
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