Preventing Cholestasis Using SMOFLipid®
Condition: Cholestasis; Psychomotor Disorders, Developmental
MeSH terms: Cholestasis; Psychomotor Disorders
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): SMOFLIPID; INTRALIPID
Intervention type(s): Drug; Drug
Intervention description(s): target dose: 3g/kg/d; target dose: 3g/kg/d
Other intervention name(s): SMOFLIPID (mixture of soy, fish, MCT and olive oil); INTRALIPID (soy bean oil)
Intervention MeSH terms: Soybean oil, phospholipid emulsion; SMOFlipid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Infant, Extremely Low Birth Weight; Parenteral Nutrition; Fish Oils; Cholestasis; Psychomotor Disorders, Developmental