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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Supportive Care
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: April 3, 2020

Interventions

  • Drug: Smoflipid 20% (investigational lipid for parenteral nutrition)
    • Dose: The targeted maximal lipid dose is 3.0 g/kg/day. In patients already receiving parenteral nutrition (PN) before starting study treatment, the lipid 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. Investigational or control drug will be infused over 20 – 24 hours, as per hospital policy, at a weight based infusion rate. The lipid emulsions will be infused into a central or peripheral vein.
  • Drug: Intralipid® 20%
    • Dose: The targeted maximal lipid dose is 3.0 g/kg/day. In patients already receiving parenteral nutrition (PN) before starting study treatment, the lipid 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. Investigational or control drug will be infused over 20 – 24 hours, as per hospital policy, at a weight based infusion rate. The lipid emulsions will be infused into a central or peripheral vein.

Arms, Groups and Cohorts

  • 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”.
  • 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”.

Clinical Trial Outcome Measures

Primary Measures

  • 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
    • Time Frame: Screening, Day 8, 15, 22, 29/end of treatment + confirmatory sample: 7 days after conjugated bilirubin level exceeds 2 mg/dl

Secondary Measures

  • Body weight (change from Baseline)
    • Time Frame: Day 1-29, and at Follow-up (+7 days) (if continued: until Day 85 + at Follow up)
  • Body length (change from Baseline)
    • Time Frame: 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)
    • Time Frame: 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 Frame: Day 29/end of treatment, if continued: Day 85/end of treatment
  • Fatty acids in plasma and red blood cell membranes (change from Baseline)
    • Time Frame: Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
  • Length of stay in hospital
    • Time Frame: Day 1- Follow up (7 days after end of treatment)
  • Ratio of number of independent bloodstream infections to number of days on study medication
    • Time Frame: Day 1-29 or -85 if continued + Follow-up
  • Ratio of the number of patients with 1 or more bloodstream infections to number of patients on study medication
    • Time Frame: Day 1-29 or -85 if continued + Follow-up
  • Number of patients who complete PN treatment without lipid minimization
    • Time Frame: 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
    • Time Frame: Day 1-29 or -85 if continued + Follow-up
  • Cumulative number of days of conjugated bilirubin levels > 1.5 mg/dL
    • Time Frame: 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
    • Time Frame: Day 1-29 or -85 if continued + Follow-up
  • Cumulative number of days patients are administered a lipid dose without lipid minimization
    • Time Frame: 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
    • Time Frame: Day 1-29 or -85 if continued + Follow-up
  • Collection of AE data
    • Time Frame: After randomization/Day 1-29 or -85: – Follow-up (7 days after end of treatment)
  • Blood sampling for safety analysis
    • Time Frame: Screening, Day 8, 15, 22, 29/end of treatment, if continued: Day 43, 57, 71, 85/end of treatment
    • (conjugated bilirubin, total bilirubin, serum triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, blood glucose, blood urea nitrogen, creatinine, C-reactive protein)
  • Blood sampling for special analysis (sterols including phytosterols, α-tocopherol)
    • Time Frame: Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
  • Holman index
    • Time Frame: Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Fresenius Kabi
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Steven A Abrams, MD, Principal Investigator, Dell Medical School at The University of Texas at Austin

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