Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Phase III Randomised Placebo Controlled Multicentre Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 313
- 试验地点
- 24
- 主要终点
- Composite measure of death or moderate/severe disability
研究概览
简要总结
Double-blind, placebo controlled Phase III trial of erythropoietin for hypoxic ischaemic encephalopathy in infants receiving hypothermia. The study aim is to determine whether Epo in conjunction with hypothermia in infants with moderate/severe hypoxic ischaemic encephalopathy (HIE) will improve neurodevelopmental outcomes at 2 years of age, without significant adverse effects, when compared to hypothermia alone.
详细描述
A lack of oxygen (hypoxia) or low blood supply (ischaemia) before or during birth can destroy cells in a newborn baby's brain. The damage caused by the lack of oxygen continues for some time afterwards. One way to try to reduce this damage is to induce hypothermia cooling the baby or just the baby's head for hours to days. Erythropoietin (Epo) given in the first week after birth shows promise as a treatment that may also help. This study is to find out whether Epo plus induced hypothermia (cooling) of near-term newborn babies who have suffered from low blood or oxygen supply to the brain at birth reduces death and disability in survivors at two years of age.
The target population is 300 newborn term or near term infants (greater than or equal to 35+0 weeks gestation) with hypoxic ischaemic encephalopathy who are receiving, or planned to receive hypothermia and who are able to be recruited in time to allow study treatment to commence before 24 hours of age.
This is a double blind, placebo controlled, parallel, 2 arm randomised, phase III multicentre trial, stratified by study site and by severity of encephalopathy at study entry.
The treatment group of 150 infants will receive human recombinant Epo, 1000 IU/kg IV on days 1, 2, 3, 5 & 7 of life. The control group will receive 0.9% sodium chloride as a placebo on days 1, 2, 3, 5 & 7 of life.
Families will be followed up every 6 months until the primary assessment of death and disability at 2 years of age.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 23 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female infants born greater than or equal to 35+0 weeks gestation and able to be randomised less than 23 hours after birth
- •One or more of the following indicators of perinatal depression:
- •Apgar less than or equal to 5 at 10 minutes after birth, OR
- •Receiving ongoing resuscitation e.g. assisted ventilation (positive pressure ventilation or CPAP) or chest compressions at 10 minutes after birth, OR
- •on cord blood or arterial or venous blood obtained at less than 60 minutes after birth, either pH less than 7.00 OR base deficit greater than or equal to 12.0 mmol/L
- •Moderate to severe encephalopathy, defined between one and six hours after birth by one or both of the following:
- •3 out of 6 modified Sarnat criteria indicating moderate/severe encephalopathy, OR
- •2 out of 6 modified Sarnat criteria plus seizure(s) requiring anticonvulsant treatment (diagnosed either clinically or using EEG monitoring) at any time prior to randomisation
- •Hypothermia treatment initiated by 6 hours ofa ge; i.e. controlled whole-body cooling planned to continue for 72 hours to a target temperature (adjusted manually or with a device) and subsequent controlled re-warming
- •Study treatment planned to start within 24 hours after birth (as soon as feasible after randomisation)
- •At least one parent greater than or equal to 18 years of age
- •Anticipated ability to collect primary endpoint at 2 years of age
- •Signed, written informed parental consent
排除标准
- •Contraindications to investigational product
- •Indication prior to randomisation for erythropoietin or any other erythropoietic stimulating agent to be given during the first two weeks of life
- •Severe intrauterine growth restriction (birth weight less than 1800g)
- •Suspected major chromosomal or congenital anomalies
- •Head circumference less than 3rd centile below the mean for gestation and gender
- •Infant for whom imminent withdrawal of care is being planned
研究组 & 干预措施
Erythropoietin
Erythropoietin (epoetin alfa) 1000 IU/kg birth weight (capped at 4000IU daily) IV infusion, on Days 1, 2, 3, 5 and 7 of age
干预措施: Epoetin Alfa (Drug)
Placebo
IV normal saline (equiv. volume), on Days 1, 2, 3, 5 and 7 of age
干预措施: Normal saline (Drug)
结局指标
主要结局
Composite measure of death or moderate/severe disability
时间窗: 2 years of age
Moderate/severe disability is defined as any cerebral palsy and a Gross Motor Function Classification Scale (GMFCS) score greater than or equal to 1), or Bayley Scale of Infant Development III (BSDIII) less than or equal to 80
次要结局
- Death(Any time from Day 1 of treatment to 2 years of age)
- Cerebral palsy (CP), assessed by paediatric assessment(2 years of age)
- Moderate/severe motor deficit(2 years of age)
- Moderate/severe cognitive deficit(2 years of age)
- Need for supplemental respiratory support (includes tracheostomy, ventilator, high flow nasal cannula, CPAP or oxygen dependency)(2 years of age)
- Need for nutritional support (includes gastrostomy or nasogastric feeds)(2 years of age)
- Major cortical visual impairment by paediatric examination(2 years of age)
- Hearing impairment status by paediatric examination - requirement for hearing aids(2 years of age)
- Epilepsy (history of 2 or more afebrile unprovoked seizures since discharge from neonatal unit where PAEAN study treatment was provided, or use of anticonvulsants at 2 years of age).(2 years of age)
- Cost of healthcare and service utilisation(2 years of age)
- Frequency of selected adverse events (AEs) of interest, including deaths(Up to 30 days post study treatment)