Phase 3 Study to Compare Safety and Efficacy of Smoflipid 20% to Intralipid 20% in Hospitalized Neonates and Infants
- Conditions
- Hospitalized Neonates and Infants, Expected to Require Parenteral Nutrition for 28 Days
- Interventions
- Drug: Smoflipid 20% (investigational lipid for parenteral nutrition)
- Registration Number
- NCT02579265
- Lead Sponsor
- Fresenius Kabi
- 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 available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 204
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Smoflipid 20% Smoflipid 20% (investigational lipid for parenteral nutrition) 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". Intralipid® 20% 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".
- Primary Outcome Measures
Name Time Method 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 Screening, Day 8, 15, 22, 29/end of treatment + confirmatory sample: 7 days after conjugated bilirubin level exceeds 2 mg/dl 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.
- Secondary Outcome Measures
Name Time Method Head Circumference (Change From Baseline) 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 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).
Time to Full Enteral or Oral Feeds Day 29/end of treatment, if continued: Day 85/end of treatment 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.
Fatty Acids in Plasma and Red Blood Cell Membranes (Change From Baseline) Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment RBC refers to red blood cells. Timepoints \>10% of Subjects (overall) are displayed.
Ratio of Independent Bloodstream Infections to Number of Days on Study Medication Day 1-29 or -85 if continued + Follow-up The Ratio is the incidence of bloodstream infection by numbers of day on study medication.
Number of Patients Who Complete PN Treatment Without Lipid Minimization Day 1-29 or -85 if continued + Follow-up The Analysis was conducted over all study phases.
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 Day 1-29 or -85 if continued + Follow-up 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
Body Weight (Change From Baseline) Day 1-29, and at Follow-up (+7 days) (if continued: until Day 85 + at Follow up) 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).
Body Length (Change From Baseline) 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 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).
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 Length of Stay in Hospital Day 1- Follow up (7 days after end of treatment) Length of stay in hospital (time from randomization to discharge) was be calculated.
NA=Not availableNumber of Patients With 1 or More Bloodstream Infections to Number of Patients on Study Medication Day 1-29 or -85 if continued + Follow-up Cumulative Number of Days Patients Are Administered a Lipid Dose Without Lipid Minimization Day 1-29 or -85 if continued + Follow-up The Analysis was performed over the entire study period.
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 Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment 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.
Trial Locations
- Locations (13)
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States
Steven & Alexandra Cohen Children's Medical Center of NY
🇺🇸New York, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
UC San Diego Medical Center
🇺🇸San Diego, California, United States
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Rady Children's Hospital San Diego
🇺🇸San Diego, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Yale - New Haven Children's Hospital
🇺🇸New Haven, Connecticut, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
The Children's Hospital at OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States