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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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ClinicalTrials.gov Identifier: NCT03563222
Recruitment Status : Not yet recruiting
First Posted : June 20, 2018
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Fresenius Kabi

Tracking Information
First Submitted Date  ICMJE June 5, 2018
First Posted Date  ICMJE June 20, 2018
Last Update Posted Date September 4, 2019
Estimated Study Start Date  ICMJE September 30, 2019
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Body weight [ Time Frame: from day 1 monthly to day 365 ]
    Body weight of patients (patients < 36 months of age)
  • 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
  • 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
  • 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
  • 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 ]
  • Sterols in plasma including phytosterols [ Time Frame: from day 1 monthly to day 365 ]
  • Change from baseline triglycerides [ Time Frame: from day 1 weekly to day 365 ]
  • Change from baseline urea nitrogen [ Time Frame: from day 1 weekly to day 365 ]
  • Change from baseline alanine aminotransferase (ALT) [ Time Frame: from day 1 weekly 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 total bilirubin [ Time Frame: from day 1 weekly to day 365 ]
  • Change from baseline gamma-glutamyl transferase (GGT) [ Time Frame: from day 1 weekly to day 365 ]
  • 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 ]
  • Change from baseline trace elements (ferritin, Zn, Se, Cu, Mn, Cr) [ 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 C-reactive protein (CRP) [ 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 red blood cell (RBC) 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 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 ]
  • 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 ]
  • Vital signs: blood pressure [ Time Frame: from day 1 monthly to day 365 ]
    Systolic and diastolic blood pressure
  • Vital signs: heart rate [ Time Frame: from day 1 monthly to day 365 ]
  • Vital signs: body temperature [ Time Frame: from day 1 monthly 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)
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2018)
  • Body weight [ Time Frame: from day 1 monthly to day 365 ]
    Body weight of patients (patients < 36 months of age)
  • 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
  • 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
  • Fatty acid profile in plasma phospholipids [ 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 plasma phospholipids
  • 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
  • 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 ]
  • Sterols in plasma including phytosterols [ Time Frame: from day 1 monthly to day 365 ]
  • Change from baseline triglycerides [ Time Frame: from day 1 weekly to day 365 ]
  • Change from baseline urea nitrogen [ Time Frame: from day 1 weekly to day 365 ]
  • Change from baseline alanine aminotransferase (ALT) [ Time Frame: from day 1 weekly 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 total bilirubin [ Time Frame: from day 1 weekly to day 365 ]
  • Change from baseline gamma-glutamyl transferase (GGT) [ Time Frame: from day 1 weekly to day 365 ]
  • 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 ]
  • Change from baseline trace elements (Fe, Zn, Se, Cu, Mn, Cr) [ 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 C-reactive protein (CRP) [ 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 red blood cell (RBC) 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 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 ]
  • 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 ]
  • Vital signs: blood pressure [ Time Frame: from day 1 monthly to day 365 ]
    Systolic and diastolic blood pressure
  • Vital signs: heart rate [ Time Frame: from day 1 monthly to day 365 ]
  • Vital signs: body temperature [ Time Frame: from day 1 monthly 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 History Complete list of historical versions of study NCT03563222 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study to Compare Smoflipid and Intralipid 20% in Pediatric Patients of 3 Months to 16 Years of Age
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE Malnutrition, Child
Intervention  ICMJE
  • 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 Name: Smoflipid® Lipid Injectible Emulsion, USP 20%
  • 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 Name: Intralipid® 20% (20% i.v. fat emulsion)
Study Arms  ICMJE
  • 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).

    Intervention: Drug: Smoflipid
  • 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.
    Intervention: Drug: Intralipid, 20%
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 19, 2018)
144
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Months to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John F Stover, MD +49 6172 686 ext 4598 john.stover@fresenius-kabi.com
Contact: Steffen Benzing, PhD +49 6172 686 ext 7709 steffen.benzing@fresenius-kabi.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03563222
Other Study ID Numbers  ICMJE SMOF-028-CP4
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fresenius Kabi
Study Sponsor  ICMJE Fresenius Kabi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Rudolph, MD University of Pittsburgh
PRS Account Fresenius Kabi
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP