Presepsin to Safely Reduce Antibiotics in Preterm Infants: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 900
- 试验地点
- 2
- 主要终点
- the incidence of culture-proven early-onset sepsis
研究概览
简要总结
In the Netherlands, more than 85% of the preterm infants born <32 weeks gestational age get antibiotics directly after birth because of the risk of infection with a bacteria. However, only 1 in 70 of these preterm babies actually has a bacterial infection. The use of antibiotics after birth can lead to problems on short term (bowel infection, infection with a bacteria later on or death) or long term (asthma, allergy, obesity).
The goal of the PRESAFE trial is to investigate whether addition of a biomarker (presepsin) to the Dutch early-onset neonatal sepsis (EOS) guideline safely reduces unnecessary empirical antibiotic exposure after birth in preterm infants born before 32 weeks gestational age. In this 874-subject multicenter, randomized clinical trial with a concurrent observational cohort, the hypothesis to be tested is that by adding presepsin to the national guideline the amount of unnecessary empirical antibiotic exposure after birth will be reduced with at least 30% without increase in infants with untreated sepsis. The study targets a population of clinical stable very preterm infants with risk factors for eary-onset neonatal sepsis. Antibiotic administration after birth is started to pre-emptively treat EOS.
By adding a presepsin-guided step to the Dutch EOS guideline for those infants qualifying for antibiotic treatment, it is assumed that the rate of antibiotic administration can be reduced. However, it is imperative that this reduction in antibiotics is not outweighed by an increase in (culture proven) EOS. Therefore, the co-primary outcomes of the study are: 1) the incidence of culture-proven EOS (non-inferiority) and 2) unnecessary antibiotics prescription i.e. antibiotic administration for ≤ 3 days when started within the first 72 hours after birth (superiority). Secondary outcomes include sepsis-related severity of illness, total number of antibiotic days when started < 72 hours after birth, and the composite outcome of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), or death until discharge from the initial hospital.
详细描述
STUDY POPULATION
All infants born at a gestational age of 24+0 to 31 6/7 weeks are eligible for enrollment. As part of standard care all infants will be screened and classified according to the Dutch EOS guideline for the indication of starting empirical antibiotics:
i. Infants at low risk of EOS who do not have an indication for empirical antibiotics according to the Dutch EOS guideline;
ii. Infants at high risk of EOS defined as: 1) suspected or confirmed diagnosis of maternal sepsis; 2) suspected or proven EOS in other infants (in case of multiple births) or infants born to mothers with previous infant with GBS disease/infection; 3) unexplained respiratory insufficiency requiring invasive mechanical ventilation and FiO2>0.40 or non-invasive ventilation with FiO2 >0.60 at time of randomization; 4) ongoing hemodynamic instability requiring inotrope medication or more than one 10 ml/kg fluid bolus at time of randomization; 5) strong clinical concern for sepsis due to physical exam findings (i.e. minimal responsiveness, poor tone).
iii. Infants at moderate risk of EOS who should be treated with empirical antibiotics based on the Dutch EOS guideline. In this group of infants the risks and benefits of receiving empiric antibiotics remain unclear and clinical equipoise is suggested.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants born at a gestational age of 24+0 to 31 6/7 weeks
- •Moderate risk of early-onset neonatal sepsis, i.e. infants who should be treated with empirical antibiotics based on the Dutch EOS guideline.
排除标准
- •low risk of early-onset neonatal sepsis who do not have an indication for empirical antibiotics according to the Dutch EOS guideline;
- •high risk of early-onset neonatal sepsis defined as:
- •suspected or confirmed diagnosis of maternal sepsis;
- •suspected or proven EOS in other infants (in case of multiple births) or infants born to mothers with previous infant with GBS disease/infection;
- •unexplained respiratory insufficiency requiring invasive mechanical ventilation and FiO2>0.40 or non-invasive ventilation with FiO2 >0.60 at time of randomization;
- •ongoing hemodynamic instability requiring inotrope medication or more than one 10 ml/kg fluid bolus at time of randomization;
- •strong clinical concern for sepsis due to physical exam findings (i.e. minimal responsiveness, poor tone).
结局指标
主要结局
the incidence of culture-proven early-onset sepsis
时间窗: 72 hours after birth
non-inferiority
presence of unnecessary antibiotics prescription
时间窗: 72 hours after birth
antibiotic administration for ≤3 days when started within the first 72 hours after birth (superiority)
次要结局
- total number of antibiotic days when started < 72 hours after birth(from birth until discharge from initial hospital (up to 6 months))
- sepsis-associated severity of illness (meningitis)(from birth until discharge from initial hospital (up to 6 months))
- sepsis-associated severity of illness (nSOFA)(from birth until discharge from initial hospital (up to 6 months))
- sepsis-associated severity of illness (death)(from birth until discharge from initial hospital (up to 6 months))
- Presence of necrotizing enterocolitis and/or late-onset sepsis and/or death(from birth until discharge from initial hospital (up to 6 months))
研究者
Douwe Visser
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)