Safely Reduce Newborn Antibiotic Exposure With the Early-onset Sepsis Calculator
- Conditions
- Early-Onset Sepsis, NeonatalEOS
- Interventions
- Device: EOS calculator
- Registration Number
- NCT05274776
- Lead Sponsor
- prof. dr. Frans B. Plötz
- Brief Summary
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.
- Detailed Description
Suspicion of EOS is often based on risk factors and nonspecific clinical symptoms, such as maternal fever during labor or rapid breathing in the newborn. The combination of the difficulty to recognize EOS in time and the risk of serious consequences of EOS not treated timely has resulted in a low threshold for the start of empirical antibiotic therapy. This has led to significant overtreatment.
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1830
- postmenstrual age of 34 weeks or more;
- 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.
- major congenital anomalies;
- language barrier (lack of effective communication or whenever it hinders understanding).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EOS Calculator 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.
- Primary Outcome Measures
Name Time Method Co-primary superiority outcome: antibiotic therapy started within 24 hours after birth 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.
Second co-primary non-inferiority outcome (safety): proportion of patients with hemodynamic support 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 0-14 days after birth First co-primary non-inferiority outcome (safety): proportion of patients with respiratory support 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 defined as any form of respiratory support (invasive ventilation, continuous positive airway pressure (CPAP), high flow nasal cannula (HFNC), low flow oxygen) during the first week of life.Fourth co-primary non-inferiority outcome (safety): proportion of patients with proven EOS 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.
- Secondary Outcome Measures
Name Time Method Antibiotic therapy started between 24-72 hours after birth 24-72 hours after birth The proportion of antibiotic therapy started for suspected and, or proven EOS if symptoms started between 24-72 hours after birth.
Duration of antibiotic therapy 0-14 days after birth The total duration of antibiotic therapy: date and time of first administration of intravenous antibiotic therapy, and date and time of the last administration of intravenous antibiotic therapy.
Questionnaire: quality of life 14-28 days after birth To get an impression of the impact of (suspected) early-onset sepsis on the quality of life (QoL) of both parents/guardians and their child, parents/guardians will be asked to fill in a questionnaire on day 14 after birth. The first part collects information on medical factors after hospitalization (side effects, number of medical visits, readmission, and medication use) and basic needs of the newborn (sleep quality of the patient, (breast)feeding success rate). The second part addresses the subjective parental/guardian evaluation of the impact of newborns' admission, and parental/guardian projection of future QoL of their newborn. Statements with six possible answers will be used: 'not at all, a little, on average, more than average, a lot, not applicable' or 'poor, fair, good, very good, excellent, not applicable'. Participants will not score on a numbered scale but tick the answer (in text) that apply best. The last part of the questionnaire collects demographic data.
Trial Locations
- Locations (10)
FlevoHospital
🇳🇱Almere, Netherlands
Amstelland Hospital
🇳🇱Amstelveen, Netherlands
OLVG
🇳🇱Amsterdam, Netherlands
Martini Hospital
🇳🇱Groningen, Netherlands
Spaarne Hospital
🇳🇱Haarlem, Netherlands
Northwest Clinics
🇳🇱Alkmaar, Netherlands
Dijklander Hospital
🇳🇱Hoorn, Netherlands
Canisius-Wilhelmina Hospital
🇳🇱Nijmegen, Netherlands
Máxima Medical Center
🇳🇱Veldhoven, Netherlands
Zaans Medical Centre
🇳🇱Zaandam, Netherlands