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

• ClinicalTrials.gov Identifier: NCT03387579
• Recruitment Status: Active, not recruiting
• First Posted: January 2, 2018
• Last Update Posted: December 29, 2021
• Sponsor: Indiana University
• Information provided by (Responsible Party): Charles P.B. Vanderpool, Indiana University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cholestasis of Parenteral Nutrition	Drug: Lipid Emulsions, Intravenous; Drug: Intralipid, 20% Intravenous Emulsion	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized to one of the two treatment arms, either composite lipid (Smoflipid) or soy-based lipid reduction.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Comparison of Composite Lipid Emulsion Containing Fish Oil to Soy-based Lipid Reduction for Cholestasis Prevention in Neonates Requiring Abdominal Surgery
• Actual Study Start Date: November 30, 2018
• Actual Primary Completion Date: March 28, 2021
• Estimated Study Completion Date: February 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Composite fish oil lipid (Smoflipid); 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: Lipid Emulsions, Intravenous; Intravenous lipid containing soy, MCT, olive, and fish oils; Other Name: Smoflipid
Active Comparator: Soy-based lipid 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

Outcome Measures

Primary Outcome Measures :

1. Cholestasis [ Time Frame: During enrollment in study, up to maximum of 12 weeks or 84 days ]
   Direct bilirubin > 2 mg/dL on two measurements 5 to 7 days apart.

Secondary Outcome Measures :

1. Growth velocity [ Time Frame: Patients weight will be measured on a daily basis while they are randomized in the study. Their weight will be recorded into the study documentation on a weekly basis up to a maximum of 12 weeks or 84 days. ]
   Change in weight as measured by grams over time
2. Growth velocity [ Time Frame: Length will be measured and recorded in the study documentation on a weekly basis up to a maximum of 12 weeks. ]
   Change in length as measured by centimeters over time
3. Growth velocity [ Time Frame: Head circumference will be measured and recorded in the study documentation on a weekly basis up to a maximum of 12 weeks. ]
   Change in head circumference as measured in centimeters over time
4. Maximum total calories from enteral intake [ Time Frame: Total daily calories will be calculated for each patient for the entire time enrolled in the study, or a maximum of 12 weeks. ]
   Maximum daily caloric intake from enteral intake as calculated by percentage of daily caloric intake.
5. Essential fatty acid deficiency [ Time Frame: Patients will have essential fatty acid panels obtained at minimum every four weeks while enrolled in the study up to a maximum of 12 weeks. ]
   Triene: tetraene ratio > 0.05
6. Difference in liver enzymes [ Time Frame: Hepatic function panel and GGT will be obtained every 2 weeks while enrolled up to a maximum of 12 weeks. ]
   Patients will have transaminase (AST, ALT), alkaline phosphatase, and gamma glutamyl transferase obtained every 2 weeks while enrolled in the study. These values will be recorded for each patient and the differences compared between the two groups.
7. Complications of prematurity [ Time Frame: Diagnoses will be documented for entirety of hospitalization, from randomization and enrollment until discharge from the hospital, up to a maximum of 12 months of age. ]
   Each patient will have their comorbid diagnoses documented with specific interest to retinopathy of prematurity and chronic lung disease or bronchopulmonary dysplasia.
8. Triglyceride concentration [ Time Frame: Triglyceride level will be obtained at a minimum of every one week for the entire enrollment of the study up to a maximum of 12 weeks. ]
   All enrolled patients will have triglyceride levels monitored weekly. If levels are found to be >250 mg/dL in any patient, their lipid dose will be decreased.
9. Length of stay [ Time Frame: Length of stay will be calculated based on documenting each patient's admission date, date leaving NICU, and date discharged from the hospital and calculating length of time between each date. An estimated maximum length of time would be 12 months. ]
   The length of stay, including time in Neonatal Intensive Care Unit (NICU) and entire hospitalization will be documented for each patient.
10. Two year development [ Time Frame: ASQ will be completed anytime during the second year of life from 2 years 0 days to 2 years 364 days of chronologic age. ]
    At two years of chronologic age ASQ will be completed by family.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Indiana

Riley Hospital for Children at IU Health

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

More Information

• Responsible Party: Charles P.B. Vanderpool, Assistant Professor of Clinical Pediatrics, Co-chair, Nutrition Support Team at Riley Hospital for Children, Medical Director, Pediatric Intestinal Rehabilitation Program, Indiana University
• ClinicalTrials.gov Identifier: NCT03387579
• Other Study ID Numbers: 1708745276
• First Posted: January 2, 2018
• Last Update Posted: December 29, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Soybean oil, phospholipid emulsion; SMOFlipid; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions