Preventing Cholestasis Using SMOFLipid®

NCT01585935 | Completed Phase 4

• 2 other identifiers: MUV-Neo22011-005456-33
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cholestasis; Psychomotor Disorders, Developmental

Keywords

Infant, Extremely Low Birth Weight; Parenteral Nutrition; Fish Oils; Cholestasis; Psychomotor Disorders, Developmental

Outcome Measures

Primary Outcomes (1)

• Incidence of parenteral nutrition associated cholestasis (PNAC)

  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 Outcomes (1)

• Bailey Scales of Infant Development III

  At 12 and 24 months corrected gestational age

Other Outcomes (2)

• Brain maturational scores assessed by amplitude integrated EEG (aEEG)

  Participants will be followed for the duration of hospital stay (expected average 14 weeks)

• Visual Evoked Potentials (VEP)

  Participants will be followed for the duration of hospital stay (expected average 14 weeks)

Study Arms (2)

Smoflipid

EXPERIMENTAL

SMOFLIPID will be used for parenteral lipid supply

Drug: SMOFLIPID

Intralipid

ACTIVE COMPARATOR

INTRALIPID will be used for parenteral lipid supply

Drug: INTRALIPID

Interventions

SMOFLIPID DRUG

target dose: 3g/kg/d

Also known as: SMOFLIPID (mixture of soy, fish, MCT and olive oil)

Smoflipid

INTRALIPID DRUG

target dose: 3g/kg/d

Also known as: INTRALIPID (soy bean oil)

Intralipid

Eligibility Criteria

• Age: 1 Day - 5 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Triplets or higher
• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University Vienna

Vienna, 1090, Austria

Location

Related Publications (4)

• Thanhaeuser M, Steyrl D, Fuiko R, Brandstaetter S, Binder C, Thajer A, Huber-Dangl M, Haiden N, Berger A, Repa A. A secondary Outcome Analysis of a Randomized Trial Using a Mixed Lipid Emulsion Containing Fish Oil in Infants with Extremely Low Birth Weight: Cognitive and Behavioral Outcome at Preschool Age. J Pediatr. 2023 Mar;254:68-74.e3. doi: 10.1016/j.jpeds.2022.10.014. Epub 2022 Oct 17.

  PMID: 36257349 DERIVED

• Thanhaeuser M, Fuiko R, Oberleitner-Leeb C, Brandstaetter S, Binder C, Thajer A, Huber-Dangl M, Haiden N, Pablik E, Berger A, Repa A. A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis. J Pediatr. 2020 Nov;226:142-148.e5. doi: 10.1016/j.jpeds.2020.06.056. Epub 2020 Jun 23.

  PMID: 32590001 DERIVED

• Binder C, Giordano V, Thanhaeuser M, Kreissl A, Huber-Dangl M, Longford N, Haiden N, Berger A, Repa A, Klebermass-Schrehof K. A Mixed Lipid Emulsion Containing Fish Oil and Its Effect on Electrophysiological Brain Maturation in Infants of Extremely Low Birth Weight: A Secondary Analysis of a Randomized Clinical Trial. J Pediatr. 2019 Aug;211:46-53.e2. doi: 10.1016/j.jpeds.2019.03.039. Epub 2019 Apr 25.

  PMID: 31030946 DERIVED

• Repa A, Binder C, Thanhaeuser M, Kreissl A, Pablik E, Huber-Dangl M, Berger A, Haiden N. A Mixed Lipid Emulsion for Prevention of Parenteral Nutrition Associated Cholestasis in Extremely Low Birth Weight Infants: A Randomized Clinical Trial. J Pediatr. 2018 Mar;194:87-93.e1. doi: 10.1016/j.jpeds.2017.11.012. Epub 2017 Dec 18.

  PMID: 29269199 DERIVED

Related Links

• Homepage of the Austrian Science Fund (FWF)
• Vienna General Hospital, Medical University of Vienna

MeSH Terms

Conditions

Cholestasis; Psychomotor Disorders; Hyperphagia

Interventions

SMOFlipid; In Situ Hybridization, Fluorescence; Olive Oil; soybean oil, phospholipid emulsion; Soybean Oil

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Plant Preparations; Biological Products; Complex Mixtures

Study Officials

• Andreas Repa, MD

  Medical University Vienna

  STUDY DIRECTOR

• Nadja Haiden, MD

  Medical University Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.MD.

Study Record Dates

• First Submitted: April 16, 2012
• First Posted: April 26, 2012
• Study Start: June 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: November 13, 2017
• Last Updated: January 9, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After publication for 10 years.
• 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

Locations

AU (1)