Back to resultsComparison of Smoflipid to Soy-based Lipid Reduction for Cholestasis Prevention in Surgical Neonates
Primary Purpose
Cholestasis of Parenteral Nutrition
Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Smoflipid 20% Lipid Emulsion for Injection
Intralipid, 20% Intravenous Emulsion
Intralipid, 20% Intravenous Emulsion
Sponsored by
About this trial
This is an interventional prevention trial for Cholestasis of Parenteral Nutrition
Eligibility 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
Sites / Locations
- Riley Hospital for Children at IU Health
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Other
Arm Label
Smoflipid 20%
Intralipid 20% Reduction
Intralipid 20% Historic
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants With Cholestasis
Cholestasis was defined as a direct bilirubin > 2 mg/dL on two measurements 5 to 7 days apart.
Secondary Outcome Measures
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.
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.
Head Circumference (OFC) Velocity
OFC velocity was calculated as difference end and start of study divided by number of days enrolled in study.
Average Total Calorie Intake
Total calorie intake, including parenteral and enteral sources, were averaged on a weekly basis.
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.
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.
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.
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.
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.
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.
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.
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.
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.
NICU Length of Stay
The length of stay at the level 4 NICU was compared between groups.
Three Year Development
During the third year of chronological age an Ages and Stages questionnaire (ASQ) will be completed by the parents.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03387579
Brief Title
Comparison of Smoflipid to Soy-based Lipid Reduction for Cholestasis Prevention in Surgical Neonates
Official Title
Comparison of Composite Lipid Emulsion Containing Fish Oil to Soy-based Lipid Reduction for Cholestasis Prevention in Neonates Requiring Abdominal Surgery
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 30, 2018 (Actual)
Primary Completion Date
March 28, 2021 (Actual)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholestasis of Parenteral Nutrition
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective patients will be randomized to one of the two treatment arms, either composite lipid containing fish oil (Smoflipid) or soy-based lipid reduction. A third arm will include retrospective patients who will act as controls and received soy-based lipid at standard dosing.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Smoflipid 20%
Arm Type
Experimental
Arm Description
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.
Arm Title
Intralipid 20% Reduction
Arm Type
Experimental
Arm Description
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.
Arm Title
Intralipid 20% Historic
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Smoflipid 20% Lipid Emulsion for Injection
Intervention Description
Intravenous lipid containing soy, MCT, olive, and fish oils at goal doses of 3 g/kg/day
Intervention Type
Drug
Intervention Name(s)
Intralipid, 20% Intravenous Emulsion
Other Intervention Name(s)
Intralipid 20% Reduction
Intervention Description
Intravenous lipid emulsion of 20% soy oil at goal doses of 1 g/kg/day
Intervention Type
Drug
Intervention Name(s)
Intralipid, 20% Intravenous Emulsion
Other Intervention Name(s)
Intralipid 20% Historic
Intervention Description
Intravenous lipid emulsion of 20% soy oil at goal doses of 2-3 g/kg/day
Primary Outcome Measure Information:
Title
Number of Participants With Cholestasis
Description
Cholestasis was defined as a direct bilirubin > 2 mg/dL on two measurements 5 to 7 days apart.
Time Frame
Patients were monitored during time enrolled in study for a maximum of up to 12 weeks or 84 days.
Secondary Outcome Measure Information:
Title
Weight Velocity
Description
Weight velocity was calculated as the difference in weight from end to start of study divided by number of days enrolled in study.
Time Frame
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.
Title
Length Velocity
Description
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.
Time Frame
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.
Title
Head Circumference (OFC) Velocity
Description
OFC velocity was calculated as difference end and start of study divided by number of days enrolled in study.
Time Frame
OFC was measured at enrollment, weekly, and end of study. Enrollment and end of study measurements used for velocity.
Title
Average Total Calorie Intake
Description
Total calorie intake, including parenteral and enteral sources, were averaged on a weekly basis.
Time Frame
Daily calorie intake was recorded and averaged on a weekly basis for duration of study enrollment up to max of 12 weeks.
Title
Number of Patients With Enteral Autonomy at End of Study
Description
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.
Time Frame
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.
Title
Number of Patients With Essential Fatty Acid Deficiency (EFAD)
Description
Essential fatty acid deficiency was defined as a triene to tetraene ratio greater than 0.05.
Time Frame
Essential fatty acid levels were measured every 4 weeks during enrollment for a maximum of up to 12 weeks.
Title
AST Change Over Time
Description
The change of AST over time was calculated and compared between groups. AST change was calculated as AST end - AST enrollment.
Time Frame
AST was recorded at enrollment and every 2 weeks while enrolled in the study up to a maximum of 12 weeks.
Title
ALT Change Over Time
Description
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.
Time Frame
ALT measured at enrollment and every 2 weeks for max 12 weeks.
Title
Alkaline Phosphatase Change Over Time
Description
Alkaline phosphatase was recorded at enrollment and every 2 weeks. The change in alkaline phosphatase was calculated as alkaline phosphatase at end minus enrollment.
Time Frame
Alkaline phosphatase was measured at enrollment and every 2 weeks for max of 12 weeks.
Title
Triglyceride Level Over Time
Description
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.
Time Frame
Serum triglyceride levels monitored at enrollment and weekly during time enrolled in study for a maximum of 12 weeks.
Title
Gamma Glutamyl Transferase (GGT) Over Time
Description
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.
Time Frame
GGT was measured at enrollment and every 2 weeks while enrolled in the study for a maximum of up to 12 weeks.
Title
Number of Patients With Retinopathy of Prematurity
Description
The rate of retinopathy of prematurity (ROP) was compared between groups. ROP was diagnosed based on ophthalmologist examination with all stages included.
Time Frame
Diagnosis was based on diagnosis during time of initial hospitalization to level 4 NICU.
Title
Number of Patients With Bronchopulmonary Dysplasia (BPD) or Chronic Lung Disease
Description
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.
Time Frame
All patient had diagnosis of BPD documented from admission at level 4 NICU.
Title
NICU Length of Stay
Description
The length of stay at the level 4 NICU was compared between groups.
Time Frame
Length of stay will be calculated based on documenting each patient's admission date and date leaving the NICU.
Title
Three Year Development
Description
During the third year of chronological age an Ages and Stages questionnaire (ASQ) will be completed by the parents.
Time Frame
ASQ will be completed anytime during the third year of life from 3 years 0 days to 3 years 364 days of chronologic age.
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Riley Hospital for Children at IU Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Comparison of Smoflipid to Soy-based Lipid Reduction for Cholestasis Prevention in Surgical Neonates
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