CholestasisPhase 4NCT01585935
Preventing Cholestasis Using SMOFLipid®
A Phase 4 study testing SMOFLIPID and INTRALIPID in people with Cholestasis and Psychomotor Disorders, Developmental, run by Medical University of Vienna at 1 site in Austria.
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. Read more about this study
- Who is it for?
- Ages 1 day to 5 days
- Conditions the study is for
- Cholestasis, Psychomotor Disorders, Developmental
- What is being tested?
- SMOFLIPID and INTRALIPID
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteAustria
- Study dates
- Jun 2012to 13 Nov 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 5 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Cholestasis, Psychomotor Disorders, Developmental
- Being tested
- SMOFLIPID, INTRALIPID
- Keywords
- Infant, Extremely Low Birth Weight, Parenteral Nutrition, Fish Oils, Cholestasis, Psychomotor Disorders, Developmental
- Medical subject headings
- Cholestasis, Psychomotor Disorders, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SMOFLIPIDDrug
Also called SMOFLIPID (mixture of soy, fish, MCT and olive oil)
target dose: 3g/kg/d
INTRALIPIDDrug
Also called INTRALIPID (soy bean oil)
target dose: 3g/kg/d
| Study group | Role | What they receive |
|---|---|---|
| Smoflipid | Experimental | SMOFLIPID will be used for parenteral lipid supply Receives: Drug: SMOFLIPID |
| Intralipid | Active comparator | INTRALIPID will be used for parenteral lipid supply Receives: Drug: INTRALIPID |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of parenteral nutrition associated cholestasis (PNAC)
PNAC definition: Two consecutive conjugated bilirubin measurements > 1.5 mg/dl
Measured: Participants will be followed for the duration of hospital stay (expected average 14 weeks)
Secondary outcomes (1)
Bailey Scales of Infant Development III
Cognitive, Motor and Language Development
Measured: At 12 and 24 months corrected gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2012 (estimated)
- Study startJun 2012
- Primary completionJun 2015
- Study completion13 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CholestasisStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nadja Haiden,MD, Medical University of Vienna
- Investigators
- Andreas Repa, MD, Study director, Medical University of ViennaNadja Haiden, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01585935
- Sponsor's protocol ID
- MUV-Neo2
- Other IDs
- 2011-005456-33
- Status last verified
- Jan 2018
- First submitted
- 16 Apr 2012
- Last updated
- 9 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: After publication of the trial, we currently plan to share IPD upon personal request.
Publications
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.
PubMed 36257349Thanhaeuser 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.
PubMed 32590001Binder 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.
PubMed 31030946Repa 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.
PubMed 29269199
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Cholestasis in Premature Infants Using SMOFLipid®
- ClinicalTrials.gov ID
- NCT01585935
- Acronym / sponsor ID
- MUV-Neo2
- Conditions
- Cholestasis, Psychomotor Disorders, Developmental
- Keywords
- Infant, Extremely Low Birth Weight, Parenteral Nutrition, Fish Oils, Cholestasis, Psychomotor Disorders, Developmental
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- 13 Nov 2017 (actual)
- First posted
- 26 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Smoflipid | Experimental | Drug: SMOFLIPIDSMOFLIPID will be used for parenteral lipid supply |
| Intralipid | Active comparator | Drug: INTRALIPIDINTRALIPID will be used for parenteral lipid supply |
Who may qualify
- Ages
- 1 day to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SMOFLIPIDAlso: SMOFLIPID (mixture of soy, fish, MCT and olive oil)target dose: 3g/kg/d | Drug | Smoflipid |
| INTRALIPIDAlso: INTRALIPID (soy bean oil)target dose: 3g/kg/d | Drug | Intralipid |
Primary outcome
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
1 secondary outcome
Bailey Scales of Infant Development III
Time frame: At 12 and 24 months corrected gestational age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2018.
- Derived from this study: PubMed 36257349Thanhaeuser 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.
- Derived from this study: PubMed 32590001Thanhaeuser 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.
- Derived from this study: PubMed 31030946Binder 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.
- Derived from this study: PubMed 29269199Repa 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.
- Homepage of the Austrian Science Fund (FWF)Link provided by the sponsor.
- Vienna General Hospital, Medical University of ViennaLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. After publication of the trial, we currently plan to share IPD upon personal request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Repa, MD study director
Medical University of Vienna
Nadja Haiden, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing SMOFLIPID and INTRALIPID in people with Cholestasis and Psychomotor Disorders, Developmental, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of parenteral nutrition associated cholestasis (PNAC) (time frame: Participants will be followed for the duration of hospital stay (expected average 14 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01585935, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2018.