Clinical trial NCT02357576: Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD
Official title: Phase 3 Study of Standard Lipid Therapy Versus Intravenous Fat Emulsion Minimization for the Prevention of Parenteral Nutrition-Associated Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cholestasis
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Seattle Children's Hospital
name: University of Florida
name: Primary Children's Hospital
name: University of Colorado, Denver
First posted: 2015-02-06
Enrollment: 22
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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
* volvulus
* intestinal atresia with \>50% bowel loss

Exclusion Criteria:

* 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

Primary outcomes:
measure: Rate of Rise of Direct Bilirubin as a Function of Time
timeFrame: 12 weeks
Secondary outcomes:
measure: Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL)
timeFrame: 12 weeks
measure: Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks)
timeFrame: 12 weeks
measure: The Time to Development of PNAC
timeFrame: 12 weeks
measure: The Time to Development of Severe PNAC
timeFrame: 12 weeks
measure: Peak Total Bilirubin Level
timeFrame: 12 weeks
measure: Peak Direct Bilirubin Level
timeFrame: 12 weeks
measure: The Prevalence of Essential Fatty Acid Deficiency (EFAD)
timeFrame: 12 weeks
measure: Adequacy of Growth as Evaluated by Z-scores for Weight
timeFrame: 12 weeks
measure: Adequacy of Growth as Evaluated by Z-scores for Height
timeFrame: 12 weeks
measure: Adequacy of Growth as Evaluated by Z-scores for Head Circumference
timeFrame: 12 weeks
measure: Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections
timeFrame: 12 weeks
measure: Bayley Scales for Infant and Toddler Development (BSID-III) at One Year
timeFrame: 1 year
measure: Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years
timeFrame: 2 years
measure: MacArthur-Bates Communicative Development Inventories (CDI)
timeFrame: 2 years
measure: Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2
timeFrame: 2 years
measure: Gross Motor Function Classification System (GMFCS)
timeFrame: 2 years
measure: Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2
timeFrame: 2 years
measure: Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2
timeFrame: 2 years
measure: Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2
timeFrame: 2 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado/Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: University of Michigan
name: Meghan A Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References: