A Multi-Centre Safety and Efficacy Study of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonates Encephalopathy in China
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Mortality
研究概览
简要总结
This study examines the effect of cord blood in the treatment of newborn infants with neonatal encephalopathy in combination with hypothermia, which is the standard treatment for this condition. The hypothesis is that the cord blood + hypothermia combination will produce better neuroprotection than the standard treatment of hypothermia alone.
详细描述
The primary aim of this study is to determine the neuroprotective effect of intravenous administration of autologous cord blood in neonates with severe encephalopathy (hypoxic ischemic encephalopathy or cerebral infarction). It is hypothesized that the administration of autologous cord blood will be safe and well tolerated in neonates with severe encephalopathy. If a neonate is born with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the neonate will receive their own cord blood. The cord blood cells are divided into 3 doses and infused at 24, 48, and 72 hours after the birth. Infants will be randomised to treatment with autologous cord blood and hypothermia or hypothermia only and followed for safety and neurodevelopmental outcome up to 18 months. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants who allocated to hypothermia and xenon will also receive autologous cord blood in 24 hours from birth through a purpose designed delivery system. Additionally, postnatal neuro-developmental outcomes in neonates with encephalopathy after autologous cord blood therapy will be measured; HIE injury to the neonate/infant brain post autologous cord blood therapy by imaging will be characterized; MRI's will be obtained per clinical routine; serum levels of selected cytokine and neurotrophic factors in neonates with HIE before and after autologous cord blood therapy will be compared and immune cell phenotype and function in neonates with HIE before and after autologous cord blood therapy will be compared.
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
- Single (Participant)
入排标准
- 年龄范围
- — 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age ≥ 34 weeks
- •Birth weight ≥ 1800 grams
- •10-minute Apgar score ≤5 or continued need for ventilation or severe acidosis, defined as pH <7.0
- •Moderate to severe encephalopathy (Sarnat II to III)
- •A moderately or severely abnormal background aEEG voltage, or seizures identified by aEEG, if monitored
- •Up to 24 hours of age
- •Autologous umbilical cord blood available to infuse 3 doses within 72 hours after birth
- •Parental informed consent
排除标准
- •Known major congenital anomalies, such as chromosomal anomalies, heart diseases
- •Major intracranial hemorrhage identified by brain ultrasonography or computed tomography
- •Severe intrauterine growth restriction (weight <1800g)
- •Severe infectious disease, such as sepsis
- •Inability to enroll by 24 hours of age
- •Volume of collected cord blood <40 ml
- •Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist
- •Parents refuse consent
研究组 & 干预措施
Cord blood with hypothermia
Autologous cord blood will be collected after birth and stored in Cord Blood Bank of hospital. All cord blood samples are routinely performed by dedicated, trained UCB collection staff and is restricted to deliveries of mothers who have given prior written informed consent for collection. If the mother delivered a baby with signs of HIE or cerebral infarction, Bank staff collected UCB utilizing standard procedures. Collected UCB was transported at roomtemperature in validated shippers to the NICU. Infusions were started when cells and study staff were available for administration and monitoring. Infants received up to 3 infusions, with the first dose as soon as possible after birth, and at, 48, and 72 postnatal hours. At the same time, babies will referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
干预措施: Autologous cord blood (Drug)
Hypothermia
Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
干预措施: Hypothermia (Device)
结局指标
主要结局
Mortality
时间窗: From birth to the age of 18 months
The relative frequency of deaths in each group.
Disability Rate
时间窗: From birth to the age of 18 months
Disability, defined as a physical or mental handicap, especially one that prevents a person from living a full, normal life or from holding a gainful job.
次要结局
- Neurodevelopment(Bayley Scores)(At the age of 18 months)
- Brain Structural Alterations(MRI)(At the age of 12 months)
- Brain Parenchyma Alterations(MRI)(At the age of 12 months)
- Intracranial Hemorrhage(MRI)(At the age of 12 months)
- Number of Adverse Events(In 72 hours)
- Number of Adverse Events(Blood Pressure)(In 72 hours)
- Number of Adverse Events(Pulse)(In 72 hours)
- Number of Adverse Events(Respiratory)(In 72 hours)
- Incidence of Complication(From birth to the age of 28 days in each treatment period)
- SDF-1 in Serum(At the age of 14 days)
- TNF-alpha in Serum(At the age of 14 days)
- IL-1 in Serum(At the age of 14 days)