Clinical trial NCT02579265: Phase 3 Study to Compare Safety and Efficacy of Smoflipid 20% to Intralipid 20% in Hospitalized Neonates and Infants
Official title: 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: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hospitalized Neonates and Infants, Expected to Require Parenteral Nutrition for 28 Days
Keywords: Parenteral nutrition
Neonates
Infants
Lipid emulsions
Intravenous
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
First posted: 2015-10-19
Enrollment: 204
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Screening, Day 8, 15, 22, 29/end of treatment + confirmatory sample: 7 days after conjugated bilirubin level exceeds 2 mg/dl
Secondary outcomes:
measure: Body Weight (Change From Baseline)
timeFrame: Day 1-29, and at Follow-up (+7 days) (if continued: until Day 85 + at Follow up)
measure: Body Length (Change From Baseline)
timeFrame: 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
measure: Head Circumference (Change From Baseline)
timeFrame: 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
measure: Time to Full Enteral or Oral Feeds
timeFrame: Day 29/end of treatment, if continued: Day 85/end of treatment
measure: Fatty Acids in Plasma and Red Blood Cell Membranes (Change From Baseline)
timeFrame: Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
measure: Length of Stay in Hospital
timeFrame: Day 1- Follow up (7 days after end of treatment)
measure: Ratio of Independent Bloodstream Infections to Number of Days on Study Medication
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: Number of Patients With 1 or More Bloodstream Infections to Number of Patients on Study Medication
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: Number of Patients Who Complete PN Treatment Without Lipid Minimization
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: Number of Patients Needing to be Withdrawn From the Study Due to Elevated Conjugated Bilirubin Levels
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: 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
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: Cumulative Number of Days Patients Are Administered a Lipid Dose Without Lipid Minimization
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: Time to Conjugated Bilirubin > 2 mg/dL (Confirmed by a Second Sample Collected 7 Days After the First)
timeFrame: Day 1-29 or -85 if continued + Follow-up
measure: Blood Sampling for Special Analysis (Sterols Including Phytosterols, α-tocopherol)
timeFrame: Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
measure: Holman Index
timeFrame: Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: New Haven
country: United States
facility: Yale - New Haven Children's Hospital
state: Connecticut
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Steven & Alexandra Cohen Children's Medical Center of NY
state: New York
city: Oklahoma City
country: United States
facility: The Children's Hospital at OU Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Dell Medical School at The University of Texas at Austin
name: Steven A Abrams, MD
role: PRINCIPAL_INVESTIGATOR
References: