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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Malnutrition, Child

Intervention / Treatment
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* Drug: Smoflipid
* Drug: Intralipid, 20%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 3 months to 16 years of age. Patients who require PN for at least 5 days/week. 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. Written informed consent from parent(s) or legal representative(s). If possible, patient assent must also be obtained (according to local law). Exclusion Criteria: Known hypersensitivity to fish, egg, soybean, or peanut proteins, or to any of the active ingredients or excipients of Smoflipid or Intralipid 20%. Hyperlipidemia or disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentration > 250 mg/dL). Inborn errors of amino acid metabolism. Cardiopulmonary instability (including pulmonary edema, cardiac insufficiency, myocardial infarction, acidosis and hemodynamic instability requiring significant vasopressor support). Hemophagocytic syndrome. Liver enzymes (either AST, or ALT, or GGT) exceeding 5 x upper limit of normal range Direct bilirubin ≥ 2.0 mg/dl INR > 2. Any known hepatic condition outside of Intestinal Failure-Associated Liver Disease (IFALD) that will increase direct bilirubin ≥ 2.0 mg/dl. Clinically significant abnormal levels of any serum electrolyte (sodium, potassium, magnesium, calcium, chloride, phosphate). Active bloodstream infection demonstrated by positive blood culture at screening. Severe renal failure including patients on renal replacement therapy. Abnormal blood pH, oxygen saturation, or carbon dioxide. Pregnancy or lactation. Participation in another clinical study. Unlikely to survive longer than 90 days.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Smoflipid<br>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<br>* 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.<br>* Other names: Smoflipid® Lipid Injectible Emulsion, USP 20%;|
| Active Comparator: Intralipid, 20%<br>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%<br>* 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.<br>* Other names: Intralipid® 20% (20% i.v. fat emulsion);|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parenteral nutrition, Pediatrics, Malnutrition, Nutritional needs