Low Dose Parenteral Fat for the Prevention of Parenteral Nutrition Associated Cholestasis in Neonates With Congenital/Acquired Gastrointestinal Disorders
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- Presence of Cholestasis
研究概览
简要总结
Neonates with congenital/acquired gastrointestinal disorders are at high risk for Parenteral Nutrition Associated Cholestasis (PNAC). Besides enteral nutrition, standard therapies to prevent and treat PNAC have been limited and marginal. Recently, the dose and composition of standard intravenous fat emulsions have implicated in the development and progression of PNAC.
In this study, neonates with congenital/acquired gastrointestinal disorders will be randomized, in a unblinded fashion, to receive either the standard dose of an intravenous omega-6 fatty acid emulsion or a low dose of an intravenous omega-6 fatty acid emulsion throughout their course of PN or until hospital discharge, death or 100 days of life, whichever comes first. The primary outcome will be the presence of cholestasis.
详细描述
Parenteral Nutrition (PN) acts as an intravenous source of both macronutrients and micronutrients when enteral feeds are not possible. Intravenous fat emulsions often supplement PN and provide a dense source of non-protein calories and essential fatty acids. Although PN is life-sustaining, it is associated with a myriad of life-threatening complications including Parenteral Nutrition Associated Cholestasis (PNAC). Children dependent on PN for an extended period of time are high risk for liver failure.
The etiology of PNAC remains poorly understood. Neonates with congenital and acquired gastrointestinal disorders are at high risk for PNAC and its subsequent complications. Examples of these gastrointestinal disorders include gastroschisis, volvulus, atresias, dysmotility and malabsorption disorders, pseudo-obstruction, and Hirschsprung's disease. These disorders often render the gut non-functional for extended periods of time. As a result, these patients become PN-dependent and develop PNAC.
Specific PN components have been implicated in the pathogenesis of PNAC. More recently, standard intravenous fat emulsions have been labeled as one of the main culprits contributing to PNAC. Standard intravenous fat emulsions are dosed as high as 4 g/kg/d and are derived from soybean and/or safflower oil, which are rich in omega-6 fatty acids and phytosterols and contain a paucity of omega-3 fatty acids. It is unclear if the dose or high omega-6 fatty acid:omega-3 fatty acid ratio and phytosterols is responsible for the development of PNAC.
The primary specific aim of this study is to determine if PNAC is related to the amount of standard intravenous fat emulsion administered to neonates with congenital/acquired gastrointestinal disorders. The investigators hypothesize that the PNAC is unrelated to the dose of intravenous fat emulsions. To test this hypothesis, neonates with congenital/acquired gastrointestinal disorders will be randomized to low dose standard soybean based parenteral fat, 1 g/kg/d, or standard dose soybean parenteral fat, 3 g/kg/d. Secondary outcomes include: mortality rate, length of stay, and anthropometric measurements at 28 days of life and at the end of the hospital stay, which is expected to be an average of 5 weeks.
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
- None
入排标准
- 年龄范围
- 1 Minute 至 5 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •congenital or acquired gastrointestinal disorder
- •age less than 5 days of life
排除标准
- •congenital intrauterine infection know to be associated with liver involvement
- •known structural liver abnormalities
- •known genetic disorders (trisomy 21, 13, and 18)
- •inborn errors of metabolism
- •infants meeting the criteria for terminal illness (ph:6.8>2 hours)
研究组 & 干预措施
low dose intravenous fat emulsion
Subjects in this arm will receive approximately 1 g/kg/d IV of intravenous soybean oil (Intralipid).
干预措施: Intralipid (Drug)
standard dose intravenous fat emulsion
Subjects in this arm will receive approximately 3 g/kg/d IV of intravenous soybean oil (Intralipid).
干预措施: Intralipid (Drug)
结局指标
主要结局
Presence of Cholestasis
时间窗: prior to 100 days of life, hospital discharge, or death whichever comes first
Cholestasis will be defined by a direct bilirubin \> 2 mg/dL
次要结局
- Mortality Rate(at the end of the hospital stay which is expected to be an average of 5 weeks)
- Anthropometric Measurements(approximately 5 weeks)
研究者
Kara L. Calkins, MD
Assistant Professor
University of California, Los Angeles