Cerebrum and Cardiac Protection With Allopurinol in Neonates With Critical Congenital Heart Disease Requiring Cardiac Surgery With Cardiopulmonary Bypass
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 236
- 试验地点
- 4
- 主要终点
- Rate of children that are considered 'too unstable for postoperative MRI'
研究概览
简要总结
Neurodevelopmental impairment due to delayed brain development and brain injury is a fundamental problem in children with critical congenital heart disease (CCHD). Significant longterm motor-, cognitive-, and behavioral problems are the result of early postnatally and perioperatively induced brain injury. Allopurinol, a xanthine oxidase inhibitor, prevents the formation of toxic free oxygen radicals, thereby limiting hypoxia-reperfusion damage. Both animal and neonatal studies suggest that administration of allopurinol reduces hypoxic-ischemic brain injury, is cardioprotective, and safe. This study aims to evaluate the efficacy and safety of allopurinol administered early postnatally and perioperatively in children with a CCHD requiring cardiac surgery with cardiopulmonary bypass.
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 1 Month（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neonates with a prenatally or postnatally confirmed diagnosis of CCHD requiring (anticipated) cardiac surgery with CPB within the first 4 weeks of life.
- •Informed consent provided by both parents.
排除标准
- •Inability to enroll the patient before the start of delivery in case of prenatal diagnosis, or 24 hours before surgery in case of postnatal diagnosis.
- •Doubt whether the aortic arch anomaly before birth requires cardiac surgery with CPB in the neonatal period.
- •Gestational age below 36 weeks and/or birth weight less than 2000 gram.
- •Surgery not requiring cardiopulmonary bypass.
- •Decision for "comfort care only".
研究组 & 干预措施
Allopurinol
干预措施: Allopurinol (Drug)
Placebo
干预措施: Mannitol (Drug)
结局指标
主要结局
Rate of children that are considered 'too unstable for postoperative MRI'
时间窗: between birth and 1 month after cardiac surgery
This decision is based on the circulatory and respiratory status of the child before the planned postoperative MRI, as included in local guidelines (not part of this protocol) of each participating center.
Incidence of mortality
时间窗: between birth and 1 month after cardiac surgery
Defined as death until one month postoperatively.
Relevant parenchymatous brain injury on postoperative MRI
时间窗: between birth and 1 month after cardiac surgery
The presence or absence of relevant (moderate/severe) parenchymatous (ischemic or hemorrhagic) brain injury on postoperative MRI will be assessed, using the T1/T2/DWI and SWI weighted images.
次要结局
- Ventricular ejection fraction (%) pre- and postoperatively(between birth and 1 month after cardiac surgery)
- Brain function: Seizure activity on aEEG (presence or absence) postnatally and postoperatively(24-36 hours after birth, 6 hours before surgery, 48-72 hours after surgery)
- Brain injury severity score on pre- and postoperative MRI(between birth and 1 month after cardiac surgery)
- Global ventricular function (normal, mildly, moderately, severely, reduced) pre- and postoperatively(between birth and 1 month after cardiac surgery)
- Neurodevelopment(at 24 months)
- Quality of Life (scores and subscores): TNO-AZL TAPQoL(at 24 months)
- Brain oxygenation: Regional cerebral oxygen saturation (%) postnatally and postoperatively(24-36 hours after birth, 6 hours before surgery, 48-72 hours after surgery)
- Volume of hypoxic-ischemic brain injury on pre- and postoperative MRI(between birth and 1 month after cardiac surgery)
- General movements and motor optimality score(at 3 months)
研究者
dr. M.J.N.L. Benders
Professor, Head of Neonatology, MD
UMC Utrecht