Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000883314
Ethics application status
Approved
Date submitted
17/02/2017
Date registered
16/06/2017
Date last updated
16/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
SMOFLipid vs Clinoleic - randomised controlled trial
Scientific title
Effect of fish oil based lipid emulsion (SMOFlipid) compared with olive oil based lipid emulsion (Clinoleic) on omega-3 fatty acid levels in preterm (<30 weeks) neonates – a randomised controlled trial.
Secondary ID [1] 291172 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parenteral nutrition associated cholestasis and liver disease 302042 0
Late onset sepsis 302043 0
Chronic lung disease 302045 0
Patent ductus arteriosis 302046 0
Premature birth- Intra-ventricular haemorrhage 303669 0
Condition category
Condition code
Inflammatory and Immune System 301677 301677 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 301678 301678 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Reproductive Health and Childbirth 303068 303068 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 - SMOFLipid 20% is a lipid formulation that contains 30% Soybean Oil, 30% Coconut Oil (Medium chain triglycerides), 25% Olive oil and 15% Fish Oil. Babies randomised to the SMOFLipid group will receive 2 grams of lipid on day 1 intravenously as part of parenteral nutrition, increasing to 3 grams of lipid on day 2 until day 7.
Intervention code [1] 297170 0
Treatment: Drugs
Comparator / control treatment
Arm 2 - ClinOleic 20% is a lipid formulation that is derived from 20% Soybean oil and 80% Olive Oil. ClinOleic 20% is the current gold standard lipid formulation in use for <29 week gestation babies. Babies randomised to the ClinOleic group will receive 2 grams of lipid on day 1 intravenously as part of parenteral nutrition, increasing to 3 grams of lipid on day 2 until day 7.
Control group
Active

Outcomes
Primary outcome [1] 301076 0
Levels (Mean +/- SD) of LC-PUFAs in plasma and red cell membrane
Timepoint [1] 301076 0
Days 1 and 7 of lipid emulsion supplementation
Secondary outcome [1] 331671 0
Total enteral and parenteral energy intake (kcal/kg/day) assessed by review of medical records and neonatal database
Timepoint [1] 331671 0
During the study period (study day 1 to 8)
Secondary outcome [2] 331672 0
Incidence of triglyceridemia/hyperlipidemia (serum triglyceride level > 2.85 mmols/L)
Timepoint [2] 331672 0
Throughout trial monitoring period (Day 1 to day 8)
Secondary outcome [3] 331673 0
Number of episodes of blood culture positive sepsis
Timepoint [3] 331673 0
Time of admission to discharge.
Secondary outcome [4] 331674 0
Degree of intraventricular haemorrhage (IVH) by ultrasound
Timepoint [4] 331674 0
From day of admission till discharge
Secondary outcome [5] 331675 0
Duration of hospital stay
Timepoint [5] 331675 0
Until dischrge
Secondary outcome [6] 331676 0
Full blood count during treatment
Timepoint [6] 331676 0
study day 1 and 8. We will record the data if full blood count was conducted for clinical reason between day 2 to 8.
Secondary outcome [7] 331677 0
Serum conjugated bilirubin level
Timepoint [7] 331677 0
At 4 weeks of age and then every 2 weeks until discharge
Secondary outcome [8] 331678 0
Death
Timepoint [8] 331678 0
Before discharge
Secondary outcome [9] 331932 0
Serum liver enzymes AST, ALT and GGT
Timepoint [9] 331932 0
At 4 weeks of age and every 2 weeks there after until discharge.
Secondary outcome [10] 335997 0
Plasma Phytosterol levels
Timepoint [10] 335997 0
Days 1 and 7 of lipid emulsion supplementation

Eligibility
Key inclusion criteria
Babies born less than 30 weeks gestation
Minimum age
1 Days
Maximum age
7 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Blood culture positive sepsis
- Thrombocytopenia (Platelet count <130 X 109/L)
- Unconjugated hyperbilirubinemia (requiring exchange transfusion)
- Metabolic disorders including lactic and/or uncompensated acidosis
- No parenteral consent
- Administration of IV lipid infusion prior to study
- Postnatal age > 7 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
We aim to recruit approximately 44 babies into the study.

Primary endpoint in the evaluation of efficacy of the lipid emulsions is plasma/RBC omega-3 LC-PUFA (EPA, DHA) levels (% of total fatty acids), omega-3 index. Based on the baseline levels of omega-3 LC-PUFA reported in previous trials (Deshpande et al. 2009 and Webb et al. 2008), sample sizes of 20 neonates per group allow detecting a difference of 1 standard deviation in plasma/RBC omega-3 LC-PUFA between the study groups with 90% power when using a univariate t-test with a significance level 0.05. Statistical power of the same magnitude will be attained for all continuously measured outcomes on LC-PUFA and their derivatives.

We anticipate a recruitment rate of 0-2 babies per week into the study, allowing for a 10% dropout rate.

References
Deshpande GC, Simmer K, Mori T, Croft K. Parenteral lipid emulsions based on olive oil compared with soybean oil in preterm (<28 weeks' gestation) neonates: a randomised controlled trial. J Pediatr Gastroenterol Nutr. 2009;49(5):619-625.

Webb AN, Hardy P, Peterkin M, Lee O, Shalley H, Croft KD, Mori TA, Heine RG, Bines JE. Tolerability and safety of olive oil-based lipid emulsion in critically ill neonates: a blinded randomized trial. Nutrition. 2008;24(11-12):1057-1064.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/06/2017
Actual
Date of last participant enrolment
Anticipated
28/09/2018
Actual
Date of last data collection
Anticipated
30/12/2018
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7481 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 15304 0
2747 - Kingswood

Funding & Sponsors
Funding source category [1] 295614 0
University
Name [1] 295614 0
Nepean Medical Research Foundation, Sydney Medical School, University of Sydney
Country [1] 295614 0
Australia
Primary sponsor type
Hospital
Name
Nepean Hospital NICU
Address
Neonatal Intensive Care Unit
Lvl 2 South Block, Nepean Hospital
Cnr Derby and Somerset St
Kingswood NSW 2747
Country
Australia
Secondary sponsor category [1] 294453 0
None
Name [1] 294453 0
Address [1] 294453 0
Country [1] 294453 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296932 0
Nepean Blue Mountains Local Health DIstrict HREC
Ethics committee address [1] 296932 0
Human Research Ethics Office
Nepean Hospital
PO BOX 63
Penrith NSW 2751
Ethics committee country [1] 296932 0
Australia
Date submitted for ethics approval [1] 296932 0
16/09/2016
Approval date [1] 296932 0
07/11/2016
Ethics approval number [1] 296932 0
HREC/16/NEPEAN/120

Summary
Brief summary
Survival of high-risk premature babies has improved significantly in the last 20 years. Feeding intolerance is a common issue seen in extremely preterm babies, and in those with conditions such as gastroschrisis, definite necrotising enterocolitis, and short bowel syndrome. Long-term support with parenteral nutrition (PN) is crucial for these babies to provide optimal nutrition at a critical stage of development.

Lipid formulations are an important component of PN, being a good source of energy, essential fatty acids (EFA), and also of long chain polyunsaturated fatty acids (LC-PUFAs).

In recent years, focus on omega-3 fatty acids has stipulated that increased omega-3 LCPUFA, mainly docosahexanoic acid (DHA), supplementation may have extra beneficial effects for extremely premature babies who have higher rates and severity of neonatal diseases of prematurity, such as late onset sepsis, necrotising enterocolitis, respiratory diseases of the newborn, and as such have a higher inflammatory status.

A recent study by Deshpande et al. (2014) examined the use of SMOFLipid, a lipid emulsion with higher omega-3 content, compared to ClinOleic, a lipid emulsion with low omega-3 content, and found that eicosapentanoic acid (EPA) levels, and F2-isoprostane (an inflammatory marker) were slightly decreased. However docosahexanoic acid (DHA) levels were found to be similar.

Soybean lipid emulsions are associated with parenteral nutrition-associated cholestasis and liver disease and studies with using pure fish oil based emulsion showed improvement in the cholestasis. The effect on phytosterol levels by lipid emulsions has not previously been studied in extremely premature neonates.
This randomised controlled trial will compare the fatty acid levels, phytosterol levels, liver function tests and conjugated bilirubin in both groups. We hypothesis that in very preterm neonates born before 29 weeks, fish oil based lipid emulsion will result in higher omega-3 fatty acids levels as compared to standard olive oil based lipid emulsion.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72474 0
Dr Girish Deshpande
Address 72474 0
Neonatal Intensive Care Unit
Lvl 2 South Block, Nepean Hospital
Cnr Derby and Somerset St
Kingswood NSW 2747
Country 72474 0
Australia
Phone 72474 0
+61 (02) 4734 2121
Fax 72474 0
+61 (02) 4734 2698
Email 72474 0
girish.deshpande@health.nsw.gov.au
Contact person for public queries
Name 72475 0
Dr Girish Deshpande
Address 72475 0
Neonatal Intensive Care Unit
Lvl 2 South Block, Nepean Hospital
Cnr Derby and Somerset St
Kingswood NSW 2747
Country 72475 0
Australia
Phone 72475 0
+61 (02) 4734 2121
Fax 72475 0
+61 (02) 4734 2698
Email 72475 0
girish.deshpande@health.nsw.gov.au
Contact person for scientific queries
Name 72476 0
Dr Girish Deshpande
Address 72476 0
Neonatal Intensive Care Unit
Lvl 2 South Block, Nepean Hospital
Cnr Derby and Somerset St
Kingswood NSW 2747
Country 72476 0
Australia
Phone 72476 0
+61 (02) 4734 2121
Fax 72476 0
+61 (02) 4734 2698
Email 72476 0
girish.deshpande@health.nsw.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23491Study protocol  girish.deshpande@health.nsw.gov.au

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.