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

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ClinicalTrials.gov Identifier: NCT02579265
Recruitment Status : Recruiting
First Posted : October 19, 2015
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Fresenius Kabi

Tracking Information
First Submitted Date  ICMJE October 15, 2015
First Posted Date  ICMJE October 19, 2015
Last Update Posted Date February 6, 2019
Study Start Date  ICMJE December 2015
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2015)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02579265 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2015)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2015)
  • 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, 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study to Compare Safety and Efficacy of Smoflipid 20% to Intralipid 20% in Hospitalized Neonates and Infants
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Hospitalized Neonates and Infants, Expected to Require Parenteral Nutrition for 28 Days
Intervention  ICMJE
  • 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.

Study Arms  ICMJE
  • 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".
    Intervention: Drug: Smoflipid 20% (investigational lipid for parenteral nutrition)
  • 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".
    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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 15, 2015)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02579265
Other Study ID Numbers  ICMJE SMOF-018-CP3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fresenius Kabi
Study Sponsor  ICMJE Fresenius Kabi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Steven A Abrams, MD Dell Medical School at The University of Texas at Austin
PRS Account Fresenius Kabi
Verification Date February 2019

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