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Trial registered on ANZCTR


Registration number
ACTRN12612001151820
Ethics application status
Approved
Date submitted
25/10/2012
Date registered
31/10/2012
Date last updated
14/11/2018
Date data sharing statement initially provided
14/11/2018
Date results information initially provided
14/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Immunonutrition in liver surgery
Scientific title
Effect of Preoperative Immunonutrition on Outcome in Patients Undergoing Partial Hepatectomy: A Randomised Pilot Study
Secondary ID [1] 281439 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with liver cancer requiring resection 287698 0
Condition category
Condition code
Cancer 288037 288037 0 0
Liver
Diet and Nutrition 288068 288068 0 0
Other diet and nutrition disorders
Inflammatory and Immune System 288069 288069 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomised to either preoperative supplemental nutrition with IMPACT (Nestle) or to standard care (usually, no supplementation).
Patients randomized to the treatment arm will be provided with a prescription for IMPACT and instructions on intake. They will be asked to consume 3 x 237 ml tetra packs daily (1000 kcal providing 12.6 g arginine and 3.3 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), in addition to their usual intake of their normal meals and snacks, for the 5 consecutive days immediately preceding day of surgery.
Intervention code [1] 285945 0
Treatment: Other
Comparator / control treatment
Those randomized to the control arm will be advised to continue with their usual oral intake. If any of these patients are found to have malnutrition, defined as involuntary weight loss of at least 5% or 10% of their usual body weight in 1 or 6 months respectively, or a BMI of < 18.5 (ASPEN 2002), they will be provided with an alternative nutritional supplement drink (Ensure Powder) and will be advised to take 50 grams of powder with 200ml of milk or 80 grams of powder with 200mls of water (1.5kcal/ml) twice daily, in addition to their usual intake of their normal meals and snacks, for the 5 consecutive days immediately preceding day of surgery.
Control group
Active

Outcomes
Primary outcome [1] 288244 0
Postoperative immune and inflammatory status which includes C-reactive protein, total lymphocytes, CD3, CD4, CD8, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). These will be assessed on blood samples by ELISA (cytokines), flow cytometry (CD3,4,8), and standard laboratory techniques (CRP, lymphocytes).
Timepoint [1] 288244 0
Postoperative days 1, 3, and 5.
Secondary outcome [1] 299684 0
Postoperative infectious complications (for example, wound infection, urinary tract infection, pneumonia). These will be assessed usng bedside chart review according to relevant signs and symptoms, positive cultures and whether antibiotic treatment is prescribed.
Timepoint [1] 299684 0
Assessed daily over the first 30 postoperative days.
Secondary outcome [2] 299685 0
Change in total body protein as measured by neutron activation scanning.
Timepoint [2] 299685 0
Assessed at three individual time points; day prior to surgery and postoperative days 7 and 30.
Secondary outcome [3] 299686 0
Ischaemia-reperfusion injury to the liver assessed on biopsied tissue taken at surgery from the resected liver by measuring mitochodrial function and oxidative stress. Antioxidant status, as it pertains to mitochondrial function, will be determined using TBARS (thiobarbituric acid reactive substances) as an index of lipid peroxidation and oxidative stress in tissue samples. Reactive oxygen species determination will be performed and markers of damage (for example protein carbonyls, lipid peroxides etc) assessed using commercially available kits. Mitochondrial respiration flux will be determined using a high resolution respirometry oxygraph (OROBOROS Oxygraph 2K, Anton paar, Graz, Austria) with a substrate inhibitor protocol that allows rapid analysis of respiratory chain function and integrity in tissue homogenates obtained from the liver sample.
Timepoint [3] 299686 0
Day of surgery.

Eligibility
Key inclusion criteria
Scheduled for hepatic resection of primary or secondary liver cancer
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diabetes
2. Immunosuppression
3. Cirrhosis (biopsy proven or fibroscan result)
4. Chemotherapy within the 3 weeks prior to study entry
5. Taking fish oil supplements
6. Not able to take oral supplements
7. Pregnant or likely to become pregnant during the study period

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)
Allocation is by sequentially numbered sealed envelope following enrolment of eligible patients at pre-admission clinics.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation with randomisation sequence generated by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4647 0
New Zealand
State/province [1] 4647 0
Auckland

Funding & Sponsors
Funding source category [1] 286206 0
Charities/Societies/Foundations
Name [1] 286206 0
Dietitians New Zealand
Address [1] 286206 0
P O Box 5065, Lambton Quay, Wellington 6145
Country [1] 286206 0
New Zealand
Funding source category [2] 301175 0
Charities/Societies/Foundations
Name [2] 301175 0
Australasian Society for Parenteral and Enteral Nutrition
Address [2] 301175 0
33 Milgate Drive
Mornington
Vic, 3931
Australia
Country [2] 301175 0
Australia
Funding source category [3] 301176 0
Charities/Societies/Foundations
Name [3] 301176 0
A+ Trust
Address [3] 301176 0
Auckland District Health Board
Auckland City Hospital
2 Park Road
Grafton
Auckland 1023
Country [3] 301176 0
New Zealand
Primary sponsor type
Individual
Name
Assoc. Prof. Lindsay Plank
Address
Department of Surgery, University of Auckland, Private Bag 92019, Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 285016 0
Individual
Name [1] 285016 0
Dr Adam Bartlett
Address [1] 285016 0
Department of Surgery, University of Auckland, Private Bag 92019, Auckland 1142
Country [1] 285016 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288281 0
Northern A
Ethics committee address [1] 288281 0
Ministry of Health
PO Box 5013
Wellington 6145
Ethics committee country [1] 288281 0
New Zealand
Date submitted for ethics approval [1] 288281 0
Approval date [1] 288281 0
02/10/2012
Ethics approval number [1] 288281 0
NTX/12/06/056

Summary
Brief summary
Immunonutrition enriched in arginine and omega-3 fatty acids (from fish oil) provided as a preoperative supplement to patients undergoing gastrointestinal surgery has been shown to almost halve postoperative infectious complications. To date, this treatment has not been investigated in patients undergoing liver surgery, except in one small study published in a Japanese medical journal. We will randomise patients scheduled for liver resection to an immunonutrition supplement to be taken preoperatively for 5 days or to standard care. Body composition assessments will be performed pre- and post-surgery and patients will be followed for 30 d post-surgery for complications. During liver resection, the liver is rendered ischaemic for a period of time before reperfusion occurs. Liver dysfunction together with mitochondrial dysfunction resulting in oxidative stress and an increased inflammatory reaction is a consequence of this ischaemia-reperfusion injury. This has been demonstrated in animal studies in which arginine and omega-3 acids have been shown to ameliorate the injury. Liver tissue samples will be collected at time of surgery for analysis of mitochondrial function and oxidative stress. The current pilot study is intended to examine the effects of preoperative nutrition with immune-modulatory properties on postoperative outcome in these patients in terms of liver mitochondrial function and oxidative stress, inflammatory response, muscle loss, and complication rates. These data will provide the foundation for a larger scale study with infectious complications as a primary end-point.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34873 0
A/Prof Lindsay Plank
Address 34873 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland
Country 34873 0
New Zealand
Phone 34873 0
+6499236949
Fax 34873 0
Email 34873 0
l.plank@auckland.ac.nz
Contact person for public queries
Name 18120 0
Mrs Kylie Russell
Address 18120 0
Auckland City Hospital
Nutrition Services
Level 8 Building 1
Park Road, Grafton
Private Bag 92024
Auckland 1142
Country 18120 0
New Zealand
Phone 18120 0
+64 9 307 4949 x 25084
Fax 18120 0
+64 9 377 5075
Email 18120 0
krussell@adhb.govt.nz
Contact person for scientific queries
Name 9048 0
A/Prof Associate Professor Lindsay Plank
Address 9048 0
Department of Surgery, University of Auckland, Auckland Hospital Support Building, Private Bag 92019, Auckland 1142
Country 9048 0
New Zealand
Phone 9048 0
+64 9 923 6949
Fax 9048 0
+64 9 377 9656
Email 9048 0
l.plank@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results.
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
Researchers who provide a methodologically sound proposal.
Available for what types of analyses?
To achieve the aims in the approved proposal.
How or where can data be obtained?
Access subject to approvals by Principal Investigator.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary