Phase 3 Study to Compare Safety and Efficacy of Smoflipid 20% to Intralipid 20% in Hospitalized Neonates and Infants

A Prospective, Randomized, Controlled, Double-Blind, Parallel-Group, Phase 3 Study to Compare Safety and Efficacy of Smoflipid 20% to Intralipid 20% in Hospitalized Neonates and Infants Requiring 28 Days of Parenteral Nutrition

To show the superiority in safety of Smoflipid over Intralipid® as measured by the number of study patients in each treatment group with conjugated bilirubin exceeding 2 mg/dL during the first 28 days of study treatment, confirmed by a second sample collected 7 days after the first sample.

Study Overview

• Status: Terminated
• Conditions: Hospitalized Neonates and Infants, Expected to Require Parenteral Nutrition for 28 Days
• Intervention / Treatment: Drug: Smoflipid 20% (investigational lipid for parenteral nutrition); Drug: Intralipid® 20%

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale - New Haven Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611-2991
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Nebraska
    • Omaha, Nebraska, United States, 68198-1205
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 11040
      • Steven & Alexandra Cohen Children's Medical Center of NY
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The Children's Hospital at OU Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Tennessee
    • Nashville, Tennessee, United States, 37345
      • Vanderbilt Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Neonates and infants, expected to require parenteral nutrition (PN) for 28 days
• Postmenstrual age ≥ 24 weeks
• Birth weight ≥ 750g
• Gastroschisis, duodenal, jejunal or ileal atresia, volvulus, spontaneous intestinal perforation or necrotizing enterocolitis (Bell's stage 2B or higher)
• At least 80% of nutritional needs at baseline received by PN
• Signed and dated informed consent obtained from at least one parent or legal guardian

Exclusion Criteria:

• Conjugated bilirubin > 0.6 mg/dL
• Any known pre-, intra- or posthepatic complication increasing conjugated bilirubin levels > 0.6, mg/dL during study participation
• Suspected liver disease or liver damage based on either aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) exceeding 2.5x upper limit of normal range
• Active bloodstream infection demonstrated by positive blood culture at screening
• Cystic fibrosis
• Meconium ileus
• Serum triglyceride levels > 250 mg/dL
• Cyanotic congenital heart defect
• Severe renal failure with serum creatinine > 2.0 mg/dL
• History of shock requiring vasopressors
• Anasarca
• Extracorporeal Membrane Oxygenation (ECMO)
• Known inborn errors of metabolism
• Known congenital viral infection
• Unlikely to survive longer than 28 days
• Known hypersensitivity to fish-, egg-, soya- or peanut protein or to any of the active substances or excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Smoflipid 20%; Smoflipid is a lipid emulsion containing soybean oil, MCTs (medium-chain triglycerides), olive oil, and fish oil. Smoflipid belongs to the pharmacotherapeutic group: "Solutions for parenteral nutrition, fat emulsions".	Drug: Smoflipid 20% (investigational lipid for parenteral nutrition); Dose: The targeted maximal dose is 3.0 g/kg/day. In patients already receiving parenteral nutrition (PN) before starting study treatment, the dose will either stay at 3.0 g/kg/day or be increased by 1.0 g/kg/day steps to a maximum of 3.0 g/kg/day. Smoflipid 20% will be infused over 20 - 24 hours, as per hospital policy, at a weight based infusion rate. Smoflipid 20% will be infused into a central or a peripheral vein.; Other Names: Smoflipid 20% (lipid injectable emulsion)
ACTIVE_COMPARATOR: Intralipid® 20%; Intralipid is a long-chain triglyceride emulsion derived from purified soybean oil and egg yolk phospholipids. Intralipid belongs to the pharmacotherapeutic group: "Solutions for parenteral nutrition, fat emulsions".	Drug: Intralipid® 20%; Dose: The targeted maximal dose is 3.0 g/kg/day. In patients already receiving parenteral nutrition (PN) before starting study treatment, the dose will either stay at 3.0 g/kg/day or be increased by 1.0 g/kg/day steps to a maximum of 3.0 g/kg/day. Intralipid® 20% will be infused over 20 - 24 hours, as per hospital policy, at a weight based infusion rate. Intralipid® 20% will be infused into a central or peripheral vein.; Other Names: Intralipid® 20% (a 20% intravenous fat emulsion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients in Each Treatment Group With Conjugated Bilirubin Levels > 2 mg/dL During the First 28 Days of Study Treatment, Confirmed by a Second Sample Collected 7 Days After the First Sample	Analysis of patients with Event at any timepoint of sampling (i.e. Day 8, 15, 22, 29/end of Treatment) and subsequent (i.e. +7 days) confirmation.	Screening, Day 8, 15, 22, 29/end of treatment + confirmatory sample: 7 days after conjugated bilirubin level exceeds 2 mg/dl

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight (Change From Baseline)	Data were age-standardized using growth charts as suggested by Fenton (Fenton et al., 2013) and the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS; WHO 2006, 2007).	Day 1-29, and at Follow-up (+7 days) (if continued: until Day 85 + at Follow up)
Body Length (Change From Baseline)	Data were age-standardized using growth charts as suggested by Fenton (Fenton et al., 2013) and the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS; WHO 2006, 2007).	Day 1, 8, 15, 22, 29/end of treatment, if continued: Day 36, 43, 50, 57, 64, 71, 78, 85/end of treatment, Follow-up
Head Circumference (Change From Baseline)	Data were age-standardized using growth charts as suggested by Fenton (Fenton et al., 2013) and the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS; WHO 2006, 2007).	Day 1, 8, 15, 22, 29/end of treatment, if continued: Day 36, 43, 50, 57, 64, 71, 78, 85/end of treatment, Follow-up
Time to Full Enteral or Oral Feeds	Time to full enteral or oral feeds (i.e. PN weaning) is the time from the randomization date to the date of the first full enteral or oral Feeds.	Day 29/end of treatment, if continued: Day 85/end of treatment
Fatty Acids in Plasma and Red Blood Cell Membranes (Change From Baseline)	RBC refers to red blood cells. Timepoints >10% of Subjects (overall) are displayed.	Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
Length of Stay in Hospital	Length of stay in hospital (time from randomization to discharge) was be calculated. NA=Not available	Day 1- Follow up (7 days after end of treatment)
Ratio of Independent Bloodstream Infections to Number of Days on Study Medication	The Ratio is the incidence of bloodstream infection by numbers of day on study medication.	Day 1-29 or -85 if continued + Follow-up
Number of Patients With 1 or More Bloodstream Infections to Number of Patients on Study Medication		Day 1-29 or -85 if continued + Follow-up
Number of Patients Who Complete PN Treatment Without Lipid Minimization	The Analysis was conducted over all study phases.	Day 1-29 or -85 if continued + Follow-up
Number of Patients Needing to be Withdrawn From the Study Due to Elevated Conjugated Bilirubin Levels		Day 1-29 or -85 if continued + Follow-up
Area Under the Curve for Time Period in Which Conjugated Bilirubin Levels Are > 1.5 mg/dL in Patients Who Are Not Withdrawn From the Study	The area under the curve (AUC>1.5) is defined as the area between conjugated bilirubin concentrations > 1.5 mg/dL and the horizontal line at 1.5 mg/dL, restricted by the time point of study withdrawal, if applicable. Analysis displays the summary of Area Under the Curve of Bilirubin Levels for the Time Period in Which Conjugated are >1.5 mg/dL	Day 1-29 or -85 if continued + Follow-up
Cumulative Number of Days Patients Are Administered a Lipid Dose Without Lipid Minimization	The Analysis was performed over the entire study period.	Day 1-29 or -85 if continued + Follow-up
Time to Conjugated Bilirubin > 2 mg/dL (Confirmed by a Second Sample Collected 7 Days After the First)		Day 1-29 or -85 if continued + Follow-up
Blood Sampling for Special Analysis (Sterols Including Phytosterols, α-tocopherol)		Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
Holman Index	Essential fatty acid deficiency is based on the ratio of Mead acid and Arachidonic acid (also called the triene/tetraene ratio or Holman index; Holman, 1960). A ratio of > 0.2 was considered abnormal (=essential fatty acid deficiency; Holman et al., 1979). Timepoints with >10% of patients are displayed.	Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Investigators: Principal Investigator: Steven A Abrams, MD, Dell Medical School at The University of Texas at Austin

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2015
• Primary Completion (ACTUAL): April 3, 2020
• Study Completion (ACTUAL): April 10, 2020

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (ESTIMATE): October 19, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 5, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Infants; Intravenous; Neonates; Parenteral nutrition; Lipid emulsions
• Additional Relevant MeSH Terms: Pharmaceutical Solutions; Parenteral Nutrition Solutions; Soybean oil, phospholipid emulsion; Fat Emulsions, Intravenous; SMOFlipid
• Other Study ID Numbers: SMOF-018-CP3