Effects of Closed-loop Automatic Control of the Inspiratory Fraction of Oxygen (FiO2-C) on Outcome of Extremely Preterm Infants - a Randomized Controlled Parallel Group Multicenter Trial for Safety and Efficacy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,065
- 试验地点
- 62
- 主要终点
- Primary outcome II: composite of death or neurodevelopmental impairment (NDI)
研究概览
简要总结
Extremely low gestational age neonates (ELGANs), i.e. those born at <28 weeks, frequently experience intermittent hypoxemic/hyperoxemic episodes. Observational data indicate that severe and prolonged hypoxemic episodes are associated with retinopathy of prematurity (ROP), impaired long-term development and death. Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the oxygen target range, decreases number and duration of hypo- and hyperoxemic episodes, and reduces caregivers' workload. The proposed observer-blinded randomized controlled trial was designed and will be powered to compare the effect of FiO2-C in addition to manual adjustments, in comparison with manual adjustments of FiO2 only, on death and severe complications of prematurity thought to be related to hypoxia/hyperoxia and neurodevelopmental impairment in ELGANs. The results of this trial may help to improve the quality of life of ELGANs and reduce the burden of significant morbidity as well as costs for health care and society
详细描述
Approximately 0.5% of all neonates (i.e., about 25,000 infants per year in Europe) are extremely low gestational age neonates (ELGANs), i.e. have a gestational age (GA) of <28 completed weeks at birth. ELGANs have higher incidences of mortality, retinopathy of prematurity (ROP), chronic lung disease and other risks of prematurity as well as severe neurodevelopmental impairment.
The vast majority of ELGANs require supplemental oxygen in addition to mechanical respiratory support (including CPAP). Irrespective of the SpO2 target, the vast majority of ELGANs suffers from recurrent intermittent hypoxemic and (as a consequence of inappropriate adjustments of FiO2) hyperoxemic episodes. Recurrent intermittent hypoxic episodes - i.e. wide fluctuations in oxygen levels - are associated with an increased risk of ROP and there are data that suggest that late deaths and neurodevelopmental impairment are also linked to them.
Continuous positive airway pressure (CPAP) has been shown to reduce extubation failure in preterm infants, which may in part be due to a reduced frequency and severity of apnea of prematurity and stabilized functional residual capacity during apnea. Keeping oxygen levels (i.e., SpO2) stable despite irregular breathing patterns in ELGANs, requires frequent adjustments of the FiO2 which is both challenging, time consuming, and often impossible due to limited personnel resources.
FiO2-Controllers have been developed by several manufacturers of infant ventilators. They reduce the burden of hyper-/hypoxemia in infants while being safe and accurate in very short-term studies. The effects of FiO2-C on clinically relevant outcome measures and the safety of long-term continuous application, however, have yet to be elucidated. Hence there is now a window of opportunity to assess this new technology for benefits and harms, before it is implemented into neonatal care without appropriate evaluation of its safety and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 48 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants with a gestational age (GA) at birth of 23+0/7 - 27+6/7 weeks
排除标准
- •Decision for palliative care
- •congenital anomalies
- •postnatal age > 48h
- •missing parental consent
- •lack of device enabling closed-loop automatic control of FiO2
结局指标
主要结局
Primary outcome II: composite of death or neurodevelopmental impairment (NDI)
时间窗: at 24 months of age corrected for prematurity
The primary outcome II is a composite of any of the following: • death or neurodevelopmental impairment (defined as at least one of the following components: motor disability (GMFCS 2-5), language or cognitive delay (language composite score \< 85 or cognitive composite score \< 85 on Bayley Scales of Infant Development, 3rd edition) or severe visual or hearing impairment (need for a hearing aid or cochlear implant)). In case of missing Bayley III test results, Bayley II results, other developmental test results or PARCA-R parent questionnaire results may substitute for the Bayley III test results in a hierarchical manner described in the study protocol. The primary outcome II will be analysed between the two intervention groups using chi2-test and Cochrane Mantel-Haenszel statistics will be presented (risk ratios and 95%-confidence intervals). The factors considered for randomization (center, sex and gestational age at birth (\<26 weeks and ≥26 weeks) will also be used for analysis.
Primary outcome I: composite outcome of death, severe retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC)
时间窗: until/at post-menstrual age (PMA) 36 weeks (death, BPD and NEC) and at latest at PMA 44 weeks for severity of ROP
The primary outcome I is a composite of any of the following: * Death * Severe retinopathy of prematurity (severe ROP, as defined in 7.3.1) * Chronic lung disease of prematurity (BPD, according to the physiological definition, which is described in detail in the study protocol) * Necrotizing enterocolitis (NEC, as defined in the study protocol) until discharge from hospital The primary endpoint I will be analysed between the two intervention groups using a stratified chi2-test and Cochrane Mantel-Haenszel statistics will be presented (risk ratios and 95%-confidence intervals). The factors considered for randomization (center, sex and gestational age at birth (\<26 weeks and ≥26 weeks) will also be used for analysis.
次要结局
- Neurodevelopmental impairment (NDI)(at 24 months of age corrected for prematurity)
- Bayley III: Motor composite score - numerical(at 24 months of age corrected for prematurity)
- Severe visual impairment(at 24 months of age corrected for prematurity)
- Death(24 months of age corrected for prematurity)
- Bayley III: Language composite score - numerical(at 24 months corrected age)
- ROP Severity Score(at latest at PMA 44 weeks)
- Severe ROP(at latest at PMA 44 weeks)
- Cerebral palsy(at 24 months of age corrected for prematurity)
- bronchopulmonary Dysplasia (BPD)(until 36 weeks PMA)
- Necrotizing enterocolitis (NEC)(until 36 weeks PMA)
- Bayley III. Language composite score - dichotomized(at 24 months of age corrected for prematurity)
- Bayley III: Cognitive composite score - numerical(at 24 months of age corrected for prematurity)
- Score data of modified Gross Motor Function Classification Scale (GMFCS)(at 24 months of age corrected for prematurity)
- Severe hearing impairment(at 24 months of age corrected for prematurity)
- Bayley III: Cognitive composite score - dichotomized(at 24 months of age corrected for prematurity)
- Motor disability(at 24 months of age corrected for prematurity)