Preventing Cholestasis Using SMOFLipid®

January 6, 2018 updated by: Nadja Haiden,MD, Medical University of Vienna

Preventing Cholestasis in Premature Infants Using SMOFLipid®

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.
  • Exploratory Outcomes: Brain maturation measured by amplitude integrated EEG (aEEG) and flashed visual evoked potentials as available from clinical routine examinations

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.

Study Type

Interventional

Enrollment (Actual)

230

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medical University Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 5 days (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Smoflipid
SMOFLIPID will be used for parenteral lipid supply
Drug: SMOFLIPID
target dose: 3g/kg/d
Other Names:
  • SMOFLIPID (mixture of soy, fish, MCT and olive oil)
ACTIVE_COMPARATOR: Intralipid
INTRALIPID will be used for parenteral lipid supply
Drug: INTRALIPID
target dose: 3g/kg/d
Other Names:
  • INTRALIPID (soy bean oil)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of parenteral nutrition associated cholestasis (PNAC)
Time Frame: Participants will be followed for the duration of hospital stay (expected average 14 weeks)
PNAC definition: Two consecutive conjugated bilirubin measurements > 1.5 mg/dl
Participants will be followed for the duration of hospital stay (expected average 14 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bailey Scales of Infant Development III
Time Frame: At 12 and 24 months corrected gestational age
Cognitive, Motor and Language Development
At 12 and 24 months corrected gestational age

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain maturational scores assessed by amplitude integrated EEG (aEEG)
Time Frame: Participants will be followed for the duration of hospital stay (expected average 14 weeks)
aEEG measurements of study infants performed as a part of clinical routine (as specified in the trial study protocol v 1.0-1.3)
Participants will be followed for the duration of hospital stay (expected average 14 weeks)
Visual Evoked Potentials (VEP)
Time Frame: Participants will be followed for the duration of hospital stay (expected average 14 weeks)
VEP measurements of study infants performed as a part of clinical routine (as specified in the trial study protocol v 1.0-1.3)
Participants will be followed for the duration of hospital stay (expected average 14 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Study Director: Andreas Repa, MD, Medical University Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (ACTUAL)

June 1, 2015

Study Completion (ACTUAL)

November 13, 2017

Study Registration Dates

First Submitted

April 16, 2012

First Submitted That Met QC Criteria

April 24, 2012

First Posted (ESTIMATE)

April 26, 2012

Study Record Updates

Last Update Posted (ACTUAL)

January 9, 2018

Last Update Submitted That Met QC Criteria

January 6, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MUV-Neo2
  • 2011-005456-33 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of the trial, we currently plan to share IPD upon personal request.

IPD Sharing Time Frame

After publication for 10 years.

IPD Sharing Access Criteria

We are planning to publish the protocols together with the statistical analysis plan as supplemental information. This however depends on the respective journal. Otherwise please request the study protocol together with the statistical analysis plan from the study director andreas.repa@meduniwien.ac.at

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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