Safety and Efficacy Study to Compare Smoflipid and Intralipid 20% in Pediatric Patients of 3 Months to 16 Years of Age

Prospective, Randomized (1:1), Double-Blind, Parallel-Group, Active-Controlled, Multicenter Study to Compare Safety and Efficacy of Smoflipid to Intralipid 20% in Pediatric Patients of 3 Months to 16 Years of Age Requiring Parenteral Nutrition for at Least 90 Days and up to 1 Year

Evaluate the safety and efficacy of Smoflipid compared to standard of care lipid emulsion Intralipid 20% administered via a central vein in pediatric patients 3 months to 16 years of age who require parenteral nutrition for at least 90 days and up to 1 year.

Study Overview

• Status: Terminated
• Conditions: Malnutrition, Child
• Intervention / Treatment: Drug: Smoflipid; Drug: Intralipid, 20%

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female patients 3 months to 16 years of age.
2. Patients who require PN for at least 5 days/week.
3. Patients who receive 60% or more of their total energy requirements as PN at enrollment and who are expected to receive 60% or more of their total energy requirements as PN for at least 90 days.
4. Written informed consent from parent(s) or legal representative(s). If possible, patient assent must also be obtained (according to local law).

Exclusion Criteria:

1. Known hypersensitivity to fish, egg, soybean, or peanut proteins, or to any of the active ingredients or excipients of Smoflipid or Intralipid 20%.
2. Hyperlipidemia or disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentration > 250 mg/dL).
3. Inborn errors of amino acid metabolism.
4. Cardiopulmonary instability (including pulmonary edema, cardiac insufficiency, myocardial infarction, acidosis and hemodynamic instability requiring significant vasopressor support).
5. Hemophagocytic syndrome.
6. Liver enzymes (either AST, or ALT, or GGT) exceeding 5 x upper limit of normal range
7. Direct bilirubin ≥ 2.0 mg/dl
8. INR > 2.
9. Any known hepatic condition outside of Intestinal Failure-Associated Liver Disease (IFALD) that will increase direct bilirubin ≥ 2.0 mg/dl.
10. Clinically significant abnormal levels of any serum electrolyte (sodium, potassium, magnesium, calcium, chloride, phosphate).
11. Active bloodstream infection demonstrated by positive blood culture at screening.
12. Severe renal failure including patients on renal replacement therapy.
13. Abnormal blood pH, oxygen saturation, or carbon dioxide.
14. Pregnancy or lactation.
15. Participation in another clinical study.
16. Unlikely to survive longer than 90 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Smoflipid; Smoflipid is a sterile, nonpyrogenic, white, homogenous lipid emulsion for intravenous infusion. The lipid content of Smoflipid is 0.20 g/mL, and comprises a mixture of soybean oil, medium chain triglycerides, olive oil, and fish oil. Smoflipid is indicated as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. The mean essential fatty acid content of Smoflipid is 35 mg/mL linoleic acid (omega-6) and 4.5 mg/mL α-linolenic acid (omega-3).	Drug: Smoflipid; The study drugs will be infused via a dedicated line for parenteral nutrition (PN) into a central vein using a central venous catheter or a peripherally inserted central catheter. The initial rate of infusion should be no more than 0.05 mL/minute for the first 10 to 15 minutes. If no untoward reactions occur, the rate can be changed to permit infusion of 0.5 mL/kg/hour. The individual dosage of study drug should be infused at a constant rate for 10 to 24 h/d. The administration flow rate is determined by dividing the volume of study drug by the duration of the infusion. Maximum infusion rate for lipid should not exceed 0.125 g/kg/h lipid. Study drug infusions should be given 5 to 7 days per week. Study treatment will last for a minimum of 90 consecutive days and as long as PN is indicated, up to 365 consecutive days. If the indication for PN continues after Study Day 365, PN will continue per normal institution policy.; Other Names: Smoflipid® Lipid Injectible Emulsion, USP 20%
Active Comparator: Intralipid, 20%; Intralipid 20% is a sterile, non-pyrogenic fat emulsion intended as a source of calories and essential fatty acids. Intralipid 20% is indicated as a source of calories and essential fatty acids for patients requiring parenteral nutrition for extended periods of time and as a source of essential fatty acids for prevention of essential fatty acid deficiency. The major component fatty acids are linoleic acid, oleic acid, palmitic acid, α-linolenic acid and stearic acid.	Drug: Intralipid, 20%; The study drugs will be infused via a dedicated line for parenteral nutrition (PN) into a central vein using a central venous catheter or a peripherally inserted central catheter. The initial rate of infusion should be no more than 0.05 mL/minute for the first 10 to 15 minutes. If no untoward reactions occur, the rate can be changed to permit infusion of 0.5 mL/kg/hour. The individual dosage of study drug should be infused at a constant rate for 10 to 24 h/d. The administration flow rate is determined by dividing the volume of study drug by the duration of the infusion. Maximum infusion rate for lipid should not exceed 0.125 g/kg/h lipid. Study drug infusions should be given 5 to 7 days per week. Study treatment will last for a minimum of 90 consecutive days and as long as PN is indicated, up to 365 consecutive days. If the indication for PN continues after Study Day 365, PN will continue per normal institution policy.; Other Names: Intralipid® 20% (20% i.v. fat emulsion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	Body weight of patients (patients < 36 months of age)	from day 1 monthly to day 365
Body Height	Height oder length of body (patients <36 months of age)	from day 1 monthly to day 365
Head Circumference	Circumference of head in patients > 36 months old	from day 1 monthly to day 365
Fatty Acid Profile in Total Plasma	Fatty acid profile including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid, analyzed in total plasma	from day 1 monthly to day 365
Fatty Acid Profile in Red Blood Cell Membranes	Fatty acid profile including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid, analyzed in red blood cell membranes	from day 1 monthly to day 365
Triene/Tetraene Ratio	Triene/tetraene ratio (Holman Index) in total plasma to assess essential fatty acid deficiency (EFAD)	from day 1 weekly to day 365
Number of Patients in Each Treatment Group With Direct Bilirubin Levels > 2 mg/dL		from day 1 monthly to day 365
Time Until Reaching Direct Bilirubin Levels > 2 mg/dL		from day 1 monthly to day 365
Sterols in Plasma Including Phytosterols		from day 1 monthly to day 365
Change From Baseline Triglycerides		from day 1 weekly to day 365
Change From Baseline Urea Nitrogen		from day 1 weekly to day 365
Change From Baseline Alanine Aminotransferase (ALT)		from day 1 weekly to day 365
Change From Baseline Aspartate Aminotransferase (AST)		from day 1 weekly to day 365
Change From Baseline Direct Bilirubin		from day 1 weekly to day 365
Change From Baseline Total Bilirubin		from day 1 weekly to day 365
Change From Baseline Gamma-glutamyl Transferase (GGT)		from day 1 weekly to day 365
Change Form Baseline Alkaline Phosphatase (ALP)		from day 1 weekly to day 365
Change From Baseline Creatinine		from day 1 weekly to day 365
Change From Baseline Electrolytes (Na, K, Mg, Cl,Ca, Phosphate)		from day 1 weekly to day 365
Change From Baseline Trace Elements (Ferritin, Zn, Se, Cu, Mn, Cr)		from day 1 weekly to day 365
Change From Baseline Glucose		from day 1 weekly to day 365
Change From Baseline Total Protein		from day 1 weekly to day 365
Change From Baseline C-reactive Protein (CRP)		from day 1 weekly to day 365
Change From Baseline White Blood Cell (WBC) Count		from day 1 weekly to day 365
Change From Baseline Red Blood Cell (RBC) Count		from day 1 weekly to day 365
Change From Baseline Platelet Count		from day 1 weekly to day 365
Change From Baseline Hemoglobin		from day 1 weekly to day 365
Change From Baseline Hematocrit		from day 1 weekly to day 365
Change From Baseline International Normalized Ratio (INR)		from day 1 weekly to day 365
Change From Baseline Sterols (Beta-sitosterol, Campesterol, Stigmasterol, Brassicasterol, Ergosterol, Cholesterol, Desmosterol, Lanosterol, Beta-sitostanol, Lathosterol, Squalene)		from day 1 monthly to day 365
Vital Signs: Blood Pressure	Systolic and diastolic blood pressure	from day 1 monthly to day 365
Vital Signs: Heart Rate		from day 1 monthly to day 365
Vital Signs: Body Temperature		from day 1 monthly to day 365
Adverse Events		from day 1 weekly to day 365
Genetic Polymorphisms of Fatty Acid Desaturase Genes FADS1 and FADS2	The relation between genetic polymorphisms in the fatty acid desaturase genes Fatty acid desaturase 1 (FADS1) and Fatty acid desaturase 2 (FADS2) and plasma concentrations of linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, and Mead acid, as well as relation to and EFAD (triene/tetraene ratio)	once during treatment phase (day 1 to day 365)

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Investigators: Principal Investigator: Jeffrey Rudolph, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2019
• Primary Completion (Actual): November 12, 2020
• Study Completion (Actual): July 8, 2022

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Pediatrics; Malnutrition; Parenteral nutrition; Nutritional needs
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Child Nutrition Disorders; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion; SMOFlipid
• Other Study ID Numbers: SMOF-028-CP4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No