Phase 3 Study of Standard Lipid Therapy Versus Intravenous Fat Emulsion Minimization for the Prevention of Parenteral Nutrition-Associated Liver Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 5
- 主要终点
- Rate of Rise of Direct Bilirubin as a Function of Time
研究概览
简要总结
Parenteral nutrition-associated cholestasis (PNAC) and liver disease (PNALD) are associated with significant morbidity and mortality in neonates and is felt to be exacerbated by soybean-based lipid emulsions. Much research is currently being directed at identifying ways to reduce this risk. Reduction of the dose of soybean-based lipid given as a component of parenteral nutrition is one possible strategy. In this study we will compare standard dosing of soybean-based lipid (up to 3/kg/day) with a minimized dose (1 g/kg/day) and evaluate for the development of cholestasis and adequate growth between the two groups. Longterm followup will include an assessment of neurodevelopmental outcomes at 12 and 24 months of age.
Funding source - FDA OOPD
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
- — 至 1 Year（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •neonates and infants who are at least 28 weeks corrected gestational age at the time of enrollment who are parenteral nutrition (PN) naive
- •current direct bilirubin <2 mg/dL
- •any of the following conditions:
- •meconium ileus and peritonitis
- •gastroschisis
- •omphalocele >4cm or with liver herniated outside of the abdominal cavity
- •necrotizing enterocolitis requiring surgical intervention
- •intestinal atresia with >50% bowel loss
排除标准
- •weight <1 kg
- •metabolic pathway defect which is associated with liver dysfunction in the neonatal period, including: hereditary fructose intolerance, galactosemia due to transferase deficiency and neonatal tyrosinemia, and/or disorder of lipid metabolism
- •hepatic insufficiency as documented by either a biopsy with cirrhosis and/or marked aberration in synthetic function
- •renal failure
- •primary or secondary liver disease, regardless of liver function (includes hepatitis)
- •use of extracorporeal membrane oxygenation (ECMO)
- •suspected congenital obstruction of the hepatobiliary tree
- •documented active infection which may be communicable, including infections hepatitis or HIV
- •previous receipt of choleretic agents
- •currently receiving phenobarbital or other barbiturates
- •history of PNAC
- •direct bilirubin >=2 mg/dL at time of enrollment
- •congenital or acquired anomaly which will require major cardiovascular surgery
- •major congenital or chromosomal anomaly
- •hypoxic ischemic encephalopathy
- •congenital defect of the brain
- •major seizure disorder
研究组 & 干预措施
Reduced Lipid
Subjects will receive a minimized dose (1 g/kg/day) of the soybean-based lipid component of parenteral nutrition.
干预措施: Intralipid 20% I.V. Fat Emulsion (Drug)
Standard Lipid
Subjects will receive the standard dose (up to 3 g/kg/day) of the soybean-based lipid component of parenteral nutrition.
干预措施: Intralipid 20% I.V. Fat Emulsion (Drug)
结局指标
主要结局
Rate of Rise of Direct Bilirubin as a Function of Time
时间窗: 12 weeks
The rate of rise (change over time) of direct bilirubin was compared between the two groups at different time points.
次要结局
- The Time to Development of PNAC(12 weeks)
- Peak Total Bilirubin Level(12 weeks)
- Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL)(12 weeks)
- Adequacy of Growth as Evaluated by Z-scores for Height(12 weeks)
- Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2(2 years)
- Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks)(12 weeks)
- Adequacy of Growth as Evaluated by Z-scores for Weight(12 weeks)
- Adequacy of Growth as Evaluated by Z-scores for Head Circumference(12 weeks)
- Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections(12 weeks)
- The Time to Development of Severe PNAC(12 weeks)
- Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years(2 years)
- MacArthur-Bates Communicative Development Inventories (CDI)(2 years)
- Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2(2 years)
- Peak Direct Bilirubin Level(12 weeks)
- The Prevalence of Essential Fatty Acid Deficiency (EFAD)(12 weeks)
- Gross Motor Function Classification System (GMFCS)(2 years)
- Bayley Scales for Infant and Toddler Development (BSID-III) at One Year(1 year)
- Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2(2 years)
- Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2(2 years)
研究者
Meghan A. Arnold, MD
Assistant Professor
University of Michigan