Probiotic Supplementation in Extremely Preterm Infants in Scandinavia: A Double-blinded Randomized Controlled Multicenter Trial to Reduce the Risk of Necrotizing Enterocolitis and Mortality
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,600
- 试验地点
- 2
- 主要终点
- Necrotizing enterocolitis (NEC)
研究概览
简要总结
The primary aim of this research is to determine whether supplementation with probiotics during the first weeks of life reduces the risk of necrotizing enterocolitis (NEC) and neonatal mortality and is safe to use among extremely preterm (EPT) infants born before gestational week 28.
P: The study population include EPT infants (n= 1620) born at six tertiary neonatal units in Sweden and four units in Denmark.
I: This is a double-blinded multicenter randomized controlled trial where infants in the intervention group will as soon as they tolerate 3 mL breastmilk per feed receive a probiotic combination of Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus diluted in 3 mL breastmilk and given once daily until gestational week 34.
C: The control group will receive 3 mL breastmilk without probiotic supplementation (blinded) daily.
O: Primary outcome variables is a composite endpoint of incidence of NEC and mortality. Secondary outcomes include incidence of sepsis, duration of hospital stay, use of antibiotics, feeding tolerance, growth, and body composition after hospital discharge.
Patient benefit: To provide evidence on the usage of probiotics among EPT infants that are not currently covered by clinical recommendations. As EPT infants have the highest risk for NEC and mortality our results have the potential to change current recommendations and improve patient outcomes, decrease mortality, shorten hospitalization, and decrease overall health-care costs.
详细描述
Study plan
PURPOSE AND AIMS Studies have shown conclusive results on reduced incidence of necrotizing enterocolitis (NEC) in preterm infants born after 28 gestational weeks (1, 2). However, previous research has been underpowered for extremely preterm (EPT) infants and thus, the efficacy in this group of infants is not fully eluted. Therefore, the Swedish guidelines for probiotic supplementation in neonatal care currently excludes EPT infants from being eligible to receive probiotic supplementation (3). Notably, EPT infants is the patient group with highest mortality and NEC rate, and thus most at need for strategies that can reduce this incidence (4). We believe our study design will enable to answer if probiotic supplementation can be expanded to also include EPT infants.
Overall aim The overall aim is to determine whether early probiotic supplementation can be used as a preventable nutritional intervention to reduce the risk of NEC and neonatal mortality among EPT infants (born less than 28 gestational weeks) using a double-blinded randomized control design. Probiotic supplement effect on other common neonatal morbidities will also be studied. The study will be carried out at the neonatal intensive care unit (NICU) at Karolinska University Hospital and collaborating tertiary neonatal centres in Sweden and in Denmark.
Primary aim
- To determine whether the usage of probiotic supplementation will reduce the incidence of a composite endpoint of NEC and neonatal mortality among EPT infants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 22 Weeks 至 28 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All extremly preterm infants born beween gestational age 22+0 to 27+6
排除标准
- •Patients with severe complications and low chance of survival detected wihin the first 72 hours of life
- •Patients with major congenital-anomalies
- •Patients included in other interventional trials with the same or overlapping oucome measures.
结局指标
主要结局
Necrotizing enterocolitis (NEC)
时间窗: Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks.
verified NEC \>/= Bell sage II
Death
时间窗: Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks
次要结局
- Anibiotic use(Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks)
- Feeding intolerance(Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks)
- Gut microbiome analysis(immediately after inclusion, 14 days of life, 34 week of gestational age and 12 months corrected age.)
- Sepsis(Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks)
研究者
Alexander Rakow
Alexander Rakow MD PhD, Principal Investigator, Clinical Director Department of Neonatology, Karolinska University Hospital
Region Stockholm