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

NCT03563222 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: SMOF-028-CP4
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Malnutrition, Child

Keywords

Parenteral nutrition; Pediatrics; Malnutrition; Nutritional needs

Outcome Measures

Primary Outcomes (35)

• 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)

Study Arms (2)

Smoflipid

EXPERIMENTAL

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

Intralipid, 20%

ACTIVE COMPARATOR

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%

Interventions

Smoflipid DRUG

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.

Also known as: Smoflipid® Lipid Injectible Emulsion, USP 20%

Smoflipid

Intralipid, 20% DRUG

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.

Also known as: Intralipid® 20% (20% i.v. fat emulsion)

Intralipid, 20%

Eligibility Criteria

• Age: 3 Months - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fresenius Kabi: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Child Nutrition Disorders; Hyperphagia; Malnutrition

Interventions

SMOFlipid; soybean oil, phospholipid emulsion

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was released from postmarketing requirement and the product received marketing authorization approval from the U.S. Food \& Drug Administration. Therefore, the study was early terminated after treatment of a single patient.

Results Point of Contact

• Title: Jean-Marc Lohse, PhD
• Organization: Fresenius Kabi Germany

jean-marc.lohse@fresenius-kabi.com

+49 6172

Study Officials

• Jeffrey Rudolph, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: June 20, 2018
• Study Start: December 18, 2019
• Primary Completion: November 12, 2020
• Study Completion: July 8, 2022
• Last Updated: December 12, 2022
• Results First Posted: December 12, 2022

Record last verified: 2022-11

Locations

US (1)