Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD

NCT02357576 | Completed Phase 3 Results DMC

• 2 other identifiers: HUM000754581R01FD005085-01A1
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

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

Conditions

Cholestasis

Outcome Measures

Primary Outcomes (1)

• Rate of Rise of Direct Bilirubin as a Function of Time

  The rate of rise (change over time) of direct bilirubin was compared between the two groups at different time points.

  12 weeks

Secondary Outcomes (19)

• Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL)

  12 weeks

• 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

• The Time to Development of PNAC

  12 weeks

• The Time to Development of Severe PNAC

  12 weeks

• Peak Total Bilirubin Level

  12 weeks

Study Arms (2)

Reduced Lipid

EXPERIMENTAL

Subjects will receive a minimized dose (1 g/kg/day) of the soybean-based lipid component of parenteral nutrition.

Drug: Intralipid 20% I.V. Fat Emulsion

Standard Lipid

ACTIVE COMPARATOR

Subjects will receive the standard dose (up to 3 g/kg/day) of the soybean-based lipid component of parenteral nutrition.

Drug: Intralipid 20% I.V. Fat Emulsion

Interventions

Intralipid 20% I.V. Fat Emulsion DRUG

Reduced Lipid; Standard Lipid

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: collaborator
• University of Michigan: lead
• Seattle Children's Hospital: collaborator
• Primary Children's Hospital: collaborator
• University of Colorado, Denver: collaborator

Study Sites (5)

University of Colorado/Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32601, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84132, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Cholestasis

Interventions

soybean oil, phospholipid emulsion

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Limitations and Caveats

There was a smaller sample size than expected.

Results Point of Contact

• Title: Meghan Arnold
• Organization: University of Michigan

meghanar@umich.edu

734-936-8978

Study Officials

• Meghan A Arnold, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 2, 2015
• First Posted: February 6, 2015
• Study Start: May 21, 2016
• Primary Completion: October 12, 2017
• Study Completion: November 8, 2019
• Last Updated: December 17, 2020
• Results First Posted: January 23, 2020

Record last verified: 2020-12

Locations

US (5)