Preventing Cholestasis Using SMOFLipid®

Cholestasis Clinical Trial

Official title:

Preventing Cholestasis in Premature Infants Using SMOFLipid®

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01585935
• Other study ID #: MUV-Neo2
• Secondary ID: 2011-005456-33
• Status: Completed
• Phase: Phase 4
• First received: April 16, 2012
• Last updated: January 6, 2018
• Start date: June 2012
• Est. completion date: November 13, 2017

Study information

• Verified date: January 2018
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: November 13, 2017
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 5 Days

Eligibility

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

Related Conditions & MeSH terms

• Cholestasis
• Psychomotor Disorders, Developmental

Intervention

Drug:
• SMOFLIPID
target dose: 3g/kg/d
• INTRALIPID
target dose: 3g/kg/d

Locations

Country	Name	City	State
Austria	Medical University Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Brain maturational scores assessed by amplitude integrated EEG (aEEG)	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)
Other	Visual Evoked Potentials (VEP)	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)
Primary	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	Bailey Scales of Infant Development III	Cognitive, Motor and Language Development	At 12 and 24 months corrected gestational age

External Links

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