Comparison of Smoflipid to Soy-based Lipid Reduction for Cholestasis Prevention in Surgical Neonates

Comparison of Composite Lipid Emulsion Containing Fish Oil to Soy-based Lipid Reduction for Cholestasis Prevention in Neonates Requiring Abdominal Surgery

Intestinal failure associated liver disease is a cholestatic liver disease associated with prolonged need for parenteral nutrition that can lead to such significant complications as liver failure. In the neonatal population, infants with history of intestinal resection and short bowel syndrome are at increased risk for this disease. The investigators plan to compare two possible lipid dosing preventative strategies including a composite, fish oil lipid and soy-based lipid reduction.

Study Overview

• Status: Active, not recruiting
• Conditions: Cholestasis of Parenteral Nutrition
• Intervention / Treatment: Drug: Smoflipid 20% Lipid Emulsion for Injection; Drug: Intralipid, 20% Intravenous Emulsion; Drug: Intralipid, 20% Intravenous Emulsion

Detailed Description

Intestinal failure associated liver disease (IFALD) is a cholestatic liver disease associated with prolonged need for parenteral nutrition. This disease can lead to such serious complications as liver failure and need for transplantation. In the neonatal population, short bowel syndrome, due to intestinal resection, is the most common cause of intestinal failure. While the exact cause is yet to be determined, it is felt the lipid component of parenteral nutrition is a large contributor to the development of this disease. Currently, there is no standard preventative strategy to attempt to decrease the risk of IFALD in the high risk, post-surgical neonatal population. The investigators aim to complete a randomized trial comparing two possible preventative strategies. One group will receive a composite lipid containing fish oil (Smoflipid) and the other group will receive soy-based lipid at reduced dosing.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at IU Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Neonates with anticipated need for parenteral nutrition (based on primary physicians opinion) for greater than or equal to four weeks and one of the following diagnoses:

• Anatomic: Neonate with intestinal atresia, omphalocele, gastroschisis, or volvulus with or without intestinal resection.
• Ischemic/perforation: Neonates with spontaneous intestinal perforation or necrotizing enterocolitis requiring surgical intervention.

Exclusion Criteria:

• Current weight less than 750 grams
• AST or ALT greater than 5 times the upper limit of normal within 2 weeks of enrollment
• Direct bilirubin greater than 2 mg/dL on any consecutive measurements 5 - 7 days apart within 2 weeks of enrollment
• Severe coagulopathy with INR greater than 95th percentile for age (>1.7 at less than 5 days of age, > 1.5 older than five days of age)
• Culture confirmed sepsis with positive blood, urine, or CSF culture within 2 weeks of enrollment
• Renal failure requiring dialysis
• Cyanotic heart disease requiring prostaglandin therapy
• Hypertriglyceridemia (greater than 250mg/dL) at time of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Smoflipid 20%; Patients randomized to this arm will receive the composite fish oil lipid, Smoflipid, at standard dosing up to 3 g/kg/day. Patients will be started on a dose of 1 g/kg/day and titrated up to maximum dose. As enteral nutrition is advanced the lipid dose will be weaned per study protocol and dietary recommendations.	Drug: Smoflipid 20% Lipid Emulsion for Injection; Intravenous lipid containing soy, MCT, olive, and fish oils at goal doses of 3 g/kg/day
Experimental: Intralipid 20% Reduction; Patients randomized to this arm will receive soy-based lipid (Intralipid) at a dose of 1 g/kg/day throughout their enrollment in the study.	Drug: Intralipid, 20% Intravenous Emulsion; Intravenous lipid emulsion of 20% soy oil at goal doses of 1 g/kg/day; Other Names: Intralipid 20% Reduction; Drug: Intralipid, 20% Intravenous Emulsion; Intravenous lipid emulsion of 20% soy oil at goal doses of 2-3 g/kg/day; Other Names: Intralipid 20% Historic
Other: Intralipid 20% Historic; Patients who retrospectively received soy-based lipid (Intralipid) at standard dosing of 2-3 g/kg/day were eligible for inclusion. Patients in this group were matched to prospective patients based on diagnosis, gestational age, and length of lipid therapy.	Drug: Intralipid, 20% Intravenous Emulsion; Intravenous lipid emulsion of 20% soy oil at goal doses of 1 g/kg/day; Other Names: Intralipid 20% Reduction; Drug: Intralipid, 20% Intravenous Emulsion; Intravenous lipid emulsion of 20% soy oil at goal doses of 2-3 g/kg/day; Other Names: Intralipid 20% Historic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cholestasis	Cholestasis was defined as a direct bilirubin > 2 mg/dL on two measurements 5 to 7 days apart.	Patients were monitored during time enrolled in study for a maximum of up to 12 weeks or 84 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Velocity	Weight velocity was calculated as the difference in weight from end to start of study divided by number of days enrolled in study.	Patient weight was recorded at enrollment, weekly during time enrolled, and at end of study for up to a maximum of 12 weeks. End and enrollment weights were used to calculate velocity.
Length Velocity	Length velocity was defined as the difference in length from end of study compared to enrollment divided by the number of days enrolled in study.	Length was measured at enrollment, weekly during time enrolled in study, and end of study up to a maximum of 12 weeks. End and enrollment measurements were used for velocity.
Head Circumference (OFC) Velocity	OFC velocity was calculated as difference end and start of study divided by number of days enrolled in study.	OFC was measured at enrollment, weekly, and end of study. Enrollment and end of study measurements used for velocity.
Average Total Calorie Intake	Total calorie intake, including parenteral and enteral sources, were averaged on a weekly basis.	Daily calorie intake was recorded and averaged on a weekly basis for duration of study enrollment up to max of 12 weeks.
Number of Patients With Enteral Autonomy at End of Study	Percentage of patients with enteral autonomy at time of leaving or stopping study was calculated. Enteral autonomy was defined as relying on enteral nutrition only for nutrition intake with no need for parenteral nutrition supplementation.	Enteral autonomy was recorded at the study end point for each individual patient. This end point was at time of stopping study lipid, discharge from hospital, or maximum of 12 weeks.
Number of Patients With Essential Fatty Acid Deficiency (EFAD)	Essential fatty acid deficiency was defined as a triene to tetraene ratio greater than 0.05.	Essential fatty acid levels were measured every 4 weeks during enrollment for a maximum of up to 12 weeks.
AST Change Over Time	The change of AST over time was calculated and compared between groups. AST change was calculated as AST end - AST enrollment.	AST was recorded at enrollment and every 2 weeks while enrolled in the study up to a maximum of 12 weeks.
ALT Change Over Time	The rate of change of ALT over time was compared between groups using mixed model analysis. Change of ALT was calculated as ALT at end of study compared to ALT at enrollment.	ALT measured at enrollment and every 2 weeks for max 12 weeks.
Alkaline Phosphatase Change Over Time	Alkaline phosphatase was recorded at enrollment and every 2 weeks. The change in alkaline phosphatase was calculated as alkaline phosphatase at end minus enrollment.	Alkaline phosphatase was measured at enrollment and every 2 weeks for max of 12 weeks.
Triglyceride Level Over Time	All enrolled patients had serum triglyceride levels monitored at enrollment and weekly. The triglyceride level changes was calculated using values at the end of study compared to enrollment with mean and standard deviation calculated for each treatment group.	Serum triglyceride levels monitored at enrollment and weekly during time enrolled in study for a maximum of 12 weeks.
Gamma Glutamyl Transferase (GGT) Over Time	GGT was documented at baseline and regularly intervals with level compared over time between groups. GGT was compared by treatment group for levels at end of study and enrollment.	GGT was measured at enrollment and every 2 weeks while enrolled in the study for a maximum of up to 12 weeks.
Number of Patients With Retinopathy of Prematurity	The rate of retinopathy of prematurity (ROP) was compared between groups. ROP was diagnosed based on ophthalmologist examination with all stages included.	Diagnosis was based on diagnosis during time of initial hospitalization to level 4 NICU.
Number of Patients With Bronchopulmonary Dysplasia (BPD) or Chronic Lung Disease	The rate of BPD was documented and compared between groups. BPD was diagnosed based on need for respiratory support at 28 days of age. All levels of severity were included.	All patient had diagnosis of BPD documented from admission at level 4 NICU.
NICU Length of Stay	The length of stay at the level 4 NICU was compared between groups.	Length of stay will be calculated based on documenting each patient's admission date and date leaving the NICU.
Three Year Development	During the third year of chronological age an Ages and Stages questionnaire (ASQ) will be completed by the parents.	ASQ will be completed anytime during the third year of life from 3 years 0 days to 3 years 364 days of chronologic age.

Collaborators and Investigators

• Sponsor: Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2018
• Primary Completion (Actual): March 28, 2021
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: December 3, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (Actual): January 2, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion; SMOFlipid
• Other Study ID Numbers: 1708745276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No