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
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Sponsor
- Fresenius Kabi
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Body Weight
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 3 Months to 16 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
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).
Intervention: Smoflipid (Drug)
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.
Intervention: Intralipid, 20% (Drug)
Outcomes
Primary Outcomes
Body Weight
Time Frame: from day 1 monthly to day 365
Body weight of patients (patients \< 36 months of age)
Sterols in Plasma Including Phytosterols
Time Frame: from day 1 monthly to day 365
Change From Baseline Urea Nitrogen
Time Frame: from day 1 weekly to day 365
Change From Baseline Total Bilirubin
Time Frame: from day 1 weekly to day 365
Change From Baseline Triglycerides
Time Frame: from day 1 weekly to day 365
Fatty Acid Profile in Total Plasma
Time Frame: from day 1 monthly to day 365
Fatty acid profile including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid, analyzed in total plasma
Triene/Tetraene Ratio
Time Frame: from day 1 weekly to day 365
Triene/tetraene ratio (Holman Index) in total plasma to assess essential fatty acid deficiency (EFAD)
Number of Patients in Each Treatment Group With Direct Bilirubin Levels > 2 mg/dL
Time Frame: from day 1 monthly to day 365
Time Until Reaching Direct Bilirubin Levels > 2 mg/dL
Time Frame: from day 1 monthly to day 365
Change From Baseline Aspartate Aminotransferase (AST)
Time Frame: from day 1 weekly to day 365
Change From Baseline Direct Bilirubin
Time Frame: from day 1 weekly to day 365
Change From Baseline White Blood Cell (WBC) Count
Time Frame: from day 1 weekly to day 365
Change From Baseline Platelet Count
Time Frame: from day 1 weekly to day 365
Change From Baseline Hemoglobin
Time Frame: from day 1 weekly to day 365
Change From Baseline Sterols (Beta-sitosterol, Campesterol, Stigmasterol, Brassicasterol, Ergosterol, Cholesterol, Desmosterol, Lanosterol, Beta-sitostanol, Lathosterol, Squalene)
Time Frame: from day 1 monthly to day 365
Change From Baseline Gamma-glutamyl Transferase (GGT)
Time Frame: from day 1 weekly to day 365
Change From Baseline Glucose
Time Frame: from day 1 weekly to day 365
Change From Baseline Total Protein
Time Frame: from day 1 weekly to day 365
Change From Baseline Hematocrit
Time Frame: from day 1 weekly to day 365
Change From Baseline International Normalized Ratio (INR)
Time Frame: from day 1 weekly to day 365
Adverse Events
Time Frame: from day 1 weekly to day 365
Genetic Polymorphisms of Fatty Acid Desaturase Genes FADS1 and FADS2
Time Frame: once during treatment phase (day 1 to day 365)
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)
Change From Baseline Alanine Aminotransferase (ALT)
Time Frame: from day 1 weekly to day 365
Body Height
Time Frame: from day 1 monthly to day 365
Height oder length of body (patients \<36 months of age)
Head Circumference
Time Frame: from day 1 monthly to day 365
Circumference of head in patients \> 36 months old
Change Form Baseline Alkaline Phosphatase (ALP)
Time Frame: from day 1 weekly to day 365
Change From Baseline Creatinine
Time Frame: from day 1 weekly to day 365
Change From Baseline Electrolytes (Na, K, Mg, Cl,Ca, Phosphate)
Time Frame: from day 1 weekly to day 365
Vital Signs: Blood Pressure
Time Frame: from day 1 monthly to day 365
Systolic and diastolic blood pressure
Vital Signs: Body Temperature
Time Frame: from day 1 monthly to day 365
Fatty Acid Profile in Red Blood Cell Membranes
Time Frame: from day 1 monthly to day 365
Fatty acid profile including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid, analyzed in red blood cell membranes
Change From Baseline Trace Elements (Ferritin, Zn, Se, Cu, Mn, Cr)
Time Frame: from day 1 weekly to day 365
Change From Baseline C-reactive Protein (CRP)
Time Frame: from day 1 weekly to day 365
Change From Baseline Red Blood Cell (RBC) Count
Time Frame: from day 1 weekly to day 365
Vital Signs: Heart Rate
Time Frame: from day 1 monthly to day 365
Secondary Outcomes
No secondary outcomes reported