Preventing Cholestasis Using SMOFLipid®

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Nadja Haiden,MD, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01585935
First received: April 16, 2012
Last updated: May 10, 2014
Last verified: May 2014
  Purpose

Preterm infants of extreme low birth weight (ELBW, < 1000 gram birth weight) cannot immediately be nourished with mother´s or formula milk and are typically dependent on parenteral nutrition (PN) for a prolonged period of time. This puts them at risk for liver complications of PN, namely parenteral nutrition associated cholestasis (PNAC).

Intravenous lipid emulsions (ILE) based on soy bean oil are standard of care for provision of energy and essential fatty acids in preterm infants. However, they might be implicated in the pathogenesis of PNAC.

ILEs based on pure fish oil are proposed for therapy of PNAC. Recently a lipid emulsion containing 15 % fish oil together with soy bean, olive and MCT oil has become available in Europe (SMOFLIPID®). Such a balanced lipid emulsion might be more favourable than the standard soy bean oil emulsion (Intralipid®) concerning the development of PNAC. Furthermore ILEs containing fish oil might exert a positive effect on neurodevelopment. However, there are no data so far.

The study aims to evaluate the fish oil containing ILE "SMOFlipid®" for its protective effect against PNAC in ELBW infants compared to standard treatment with the soy bean based ILE "Intralipid®". Furthermore neurodevelopment at 12 and 24 months of corrected gestational age will be investigated.


Condition Intervention Phase
Cholestasis
Psychomotor Disorders, Developmental
Drug: mixed lipid emulsion containing fish oil
Drug: Soy bean based lipid emulsion
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Preventing Cholestasis in Premature Infants Using SMOFLipid®

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Incidence of parenteral nutrition associated cholestasis (PNAC) [ Time Frame: Participants will be followed for the duration of hospital stay (expected average 14 weeks) ] [ Designated as safety issue: Yes ]
    PNAC definition: Two consecutive conjugated bilirubin measurements > 1.5 mg/dl


Secondary Outcome Measures:
  • Bailey Scales of Infant Development III [ Time Frame: At 12 and 24 months corrected gestational age ] [ Designated as safety issue: Yes ]
    Cognitive, Motor and Language Development


Estimated Enrollment: 200
Study Start Date: June 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Smoflipid
The investigational product will be used for parenteral lipid supply
Drug: mixed lipid emulsion containing fish oil
target dose: 3g/kg/d
Other Name: Smoflipid
Active Comparator: Intralipid
The investigational product will be used for parenteral lipid supply
Drug: Soy bean based lipid emulsion
target dose: 3g/kg/d
Other Name: Intralipid

Detailed Description:

BACKGROUND: Extreme low birth weight infants (ELBW, < 1000 gram birth weight) are typically dependent on parenteral nutrition (PN) for a prolonged period of time. This puts them at risk for development of liver complications of PN, namely parenteral nutrition associated cholestasis (PNAC).

Intravenous lipid emulsion (ILE) based on soy bean oil are standard of care in preterm infants, but might be implicated in the pathogenesis of PNAC. Fish oil is rich in omega-3 long chain polyunsaturated fatty acids (LC-PUFA) that particularly accumulate in liver and brain of the fetus during the last trimester of pregnancy. In pediatric patients, ILEs based on pure fish oil are proposed as a rescue therapy of PNAC.

Recently a mixed lipid emulsion containing 15 % fish oil together with soy bean , olive and MCT oil has become available for PN in Europe. Such a balanced lipid emulsion might be more favourable than the standard soy bean oil emulsion (Intralipid®) concerning the development of PNAC. Furthermore ILEs containing fish oil might exert a positive effect on neurodevelopment. However there are no data so far.

AIM: To evaluate a fish oil containing ILE (SMOFlipid®) for its prophylactic effect on PNAC in ELBW infants compared to a soy bean based ILE (Intralipid®).

STUDY DESIGN: Double blind prospective randomized trial.

  • Primary Outcome: PNAC defined as two conjugated bilirubin > 1.5 mg/dl measurements on two consecutive occasions.
  • Secondary Outcome: The most important secondary outcome is neurodevelopment at 12 and 24 months of corrected age.

HYPOTHESIS: The use of a mixed lipid emulsion containing fish oil (SMOFLIPID®) will reduce the incidence of PNAC compared to a standard soy bean oil based lipid emulsion.

  Eligibility

Ages Eligible for Study:   up to 5 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Birth weight ≤ 1000 Gram
  • Admission to the neonatal ward in the first 24 hours of life
  • Informed consent and randomization in the first 5 days of life

Exclusion Criteria:

  • Triplets or higher
  • Conjugated bilirubin > 1.5 mg/dl before inclusion to the study
  • Conditions associated with cholestasis independent of parenteral nutrition, i.e. inborn errors of metabolism, viral infections (cytomegaly virus, HIV, Hep B, Hep C), immune mediated hemolytic disease (Rhesus incompatibility), cystic fibrosis and any other primary cholestatic disease
  • Congenital neurological malformations for secondary outcome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585935

Contacts
Contact: Andreas Repa, MD 0043-1-40400 ext 3232 andreas.repa@meduniwien.ac.at
Contact: Nadja Haiden, MD 0043-1-40400 ext 3232 nadja.haiden@meduniwien.ac.at

Locations
Austria
Medical University Vienna Recruiting
Vienna, Austria, 1090
Contact: Andreas Repa, MD    0043-1-40400 ext 3232    andreas.repa@meduniwien.ac.at   
Contact: Nadja Haiden, MD    0043-1-40400 ext 3232    nadja.haiden@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
Investigators
Study Director: Andreas Repa, MD Medical University Vienna
Principal Investigator: Nadja Haiden, MD Medical University Vienna
  More Information

Additional Information:
No publications provided

Responsible Party: Nadja Haiden,MD, Assoc.Prof.MD., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01585935     History of Changes
Other Study ID Numbers: MUV-Neo2, 2011-005456-33
Study First Received: April 16, 2012
Last Updated: May 10, 2014
Health Authority: Austria: Ethikkommission
Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
Infant, Extremely Low Birth Weight
Parenteral Nutrition
Fish Oils
Cholestasis
Psychomotor Disorders, Developmental

Additional relevant MeSH terms:
Cholestasis
Psychomotor Disorders
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 19, 2014