Back to resultsSafety and Efficacy Study to Compare Smoflipid and Intralipid 20% in Pediatric Patients of 3 Months to 16 Years of Age
Primary Purpose
Malnutrition, Child
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Smoflipid
Intralipid, 20%
Sponsored by
About this trial
This is an interventional supportive care trial for Malnutrition, Child focused on measuring Parenteral nutrition, Pediatrics, Malnutrition, Nutritional needs
Eligibility Criteria
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.
Sites / Locations
- Children's Hospital of Pittsburgh of UPMC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Smoflipid
Intralipid, 20%
Arm Description
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).
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.
Outcomes
Primary Outcome Measures
Body Weight
Body weight of patients (patients < 36 months of age)
Body Height
Height oder length of body (patients <36 months of age)
Head Circumference
Circumference of head in patients > 36 months old
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
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
Triene/Tetraene Ratio
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 Until Reaching Direct Bilirubin Levels > 2 mg/dL
Sterols in Plasma Including Phytosterols
Change From Baseline Triglycerides
Change From Baseline Urea Nitrogen
Change From Baseline Alanine Aminotransferase (ALT)
Change From Baseline Aspartate Aminotransferase (AST)
Change From Baseline Direct Bilirubin
Change From Baseline Total Bilirubin
Change From Baseline Gamma-glutamyl Transferase (GGT)
Change Form Baseline Alkaline Phosphatase (ALP)
Change From Baseline Creatinine
Change From Baseline Electrolytes (Na, K, Mg, Cl,Ca, Phosphate)
Change From Baseline Trace Elements (Ferritin, Zn, Se, Cu, Mn, Cr)
Change From Baseline Glucose
Change From Baseline Total Protein
Change From Baseline C-reactive Protein (CRP)
Change From Baseline White Blood Cell (WBC) Count
Change From Baseline Red Blood Cell (RBC) Count
Change From Baseline Platelet Count
Change From Baseline Hemoglobin
Change From Baseline Hematocrit
Change From Baseline International Normalized Ratio (INR)
Change From Baseline Sterols (Beta-sitosterol, Campesterol, Stigmasterol, Brassicasterol, Ergosterol, Cholesterol, Desmosterol, Lanosterol, Beta-sitostanol, Lathosterol, Squalene)
Vital Signs: Blood Pressure
Systolic and diastolic blood pressure
Vital Signs: Heart Rate
Vital Signs: Body Temperature
Adverse Events
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)
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03563222
Brief Title
Safety and Efficacy Study to Compare Smoflipid and Intralipid 20% in Pediatric Patients of 3 Months to 16 Years of Age
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Prematurely stopped in agreement with authorities (FDA)
Study Start Date
December 18, 2019 (Actual)
Primary Completion Date
November 12, 2020 (Actual)
Study Completion Date
July 8, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fresenius Kabi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malnutrition, Child
Keywords
Parenteral nutrition, Pediatrics, Malnutrition, Nutritional needs
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Smoflipid
Arm Type
Experimental
Arm Description
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).
Arm Title
Intralipid, 20%
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Smoflipid
Other Intervention Name(s)
Smoflipid® Lipid Injectible Emulsion, USP 20%
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Intralipid, 20%
Other Intervention Name(s)
Intralipid® 20% (20% i.v. fat emulsion)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Body Weight
Description
Body weight of patients (patients < 36 months of age)
Time Frame
from day 1 monthly to day 365
Title
Body Height
Description
Height oder length of body (patients <36 months of age)
Time Frame
from day 1 monthly to day 365
Title
Head Circumference
Description
Circumference of head in patients > 36 months old
Time Frame
from day 1 monthly to day 365
Title
Fatty Acid Profile in Total Plasma
Description
Fatty acid profile including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid, analyzed in total plasma
Time Frame
from day 1 monthly to day 365
Title
Fatty Acid Profile in Red Blood Cell Membranes
Description
Fatty acid profile including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid, analyzed in red blood cell membranes
Time Frame
from day 1 monthly to day 365
Title
Triene/Tetraene Ratio
Description
Triene/tetraene ratio (Holman Index) in total plasma to assess essential fatty acid deficiency (EFAD)
Time Frame
from day 1 weekly to day 365
Title
Number of Patients in Each Treatment Group With Direct Bilirubin Levels > 2 mg/dL
Time Frame
from day 1 monthly to day 365
Title
Time Until Reaching Direct Bilirubin Levels > 2 mg/dL
Time Frame
from day 1 monthly to day 365
Title
Sterols in Plasma Including Phytosterols
Time Frame
from day 1 monthly to day 365
Title
Change From Baseline Triglycerides
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Urea Nitrogen
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Alanine Aminotransferase (ALT)
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Aspartate Aminotransferase (AST)
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Direct Bilirubin
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Total Bilirubin
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Gamma-glutamyl Transferase (GGT)
Time Frame
from day 1 weekly to day 365
Title
Change Form Baseline Alkaline Phosphatase (ALP)
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Creatinine
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Electrolytes (Na, K, Mg, Cl,Ca, Phosphate)
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Trace Elements (Ferritin, Zn, Se, Cu, Mn, Cr)
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Glucose
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Total Protein
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline C-reactive Protein (CRP)
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline White Blood Cell (WBC) Count
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Red Blood Cell (RBC) Count
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Platelet Count
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Hemoglobin
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline Hematocrit
Time Frame
from day 1 weekly to day 365
Title
Change From Baseline International Normalized Ratio (INR)
Time Frame
from day 1 weekly to day 365
Title
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
Title
Vital Signs: Blood Pressure
Description
Systolic and diastolic blood pressure
Time Frame
from day 1 monthly to day 365
Title
Vital Signs: Heart Rate
Time Frame
from day 1 monthly to day 365
Title
Vital Signs: Body Temperature
Time Frame
from day 1 monthly to day 365
Title
Adverse Events
Time Frame
from day 1 weekly to day 365
Title
Genetic Polymorphisms of Fatty Acid Desaturase Genes FADS1 and FADS2
Description
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)
Time Frame
once during treatment phase (day 1 to day 365)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Rudolph, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study to Compare Smoflipid and Intralipid 20% in Pediatric Patients of 3 Months to 16 Years of Age
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