Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000666224
Ethics application status
Approved
Date submitted
18/04/2018
Date registered
24/04/2018
Date last updated
9/10/2023
Date data sharing statement initially provided
2/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Reversing malnutrition with targeted enteral feeding in patients awaiting liver transplantation: a randomized controlled trial
Scientific title
Reversing malnutrition with targeted enteral feeding in patients awaiting liver transplantation: a randomized controlled trial
Secondary ID [1] 294619 0
Nil known
Universal Trial Number (UTN)
Trial acronym
REVITALIZE
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Liver disease 307451 0
Malnutrition 307452 0
Liver transplant 307453 0
Sarcopenia 307454 0
Condition category
Condition code
Diet and Nutrition 306538 306538 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 306539 306539 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Musculoskeletal 306590 306590 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nasogastric feeding with Isosource 2.0 (energy-dense polymeric complete enteral formula) for eligible malnourished patients awaiting liver transplant.
Nasogastric feeds will be administered overnight to provide 75% of the patient's energy requirements, with oral diet making up the remaining 25%.
The duration of nasogastric feeding will be for the length of time the patient is on transplant waiting list (typically 1-5 months).
Patient compliance will be monitored by regularity of enteral feed ordering and enteral feed return (at monthly review).
Intervention code [1] 300923 0
Treatment: Other
Comparator / control treatment
The control group will receive nutritional advice and a meal plan from the liver transplant unit dietitian aimed at meeting their calorie targets. Dietary advice will follow current best-practice protocols, with patients encouraged to consume a HEHP diet throughout the day, with additional high-protein oral nutritional supplements as required
Control group
Active

Outcomes
Primary outcome [1] 305544 0
Change in handgrip strength prior to liver transplant, as measured by handgrip dynamometry.
Timepoint [1] 305544 0
Baseline, 2 weeks, 4 weeks (primary endpoint) after enrolment, then every 4 weeks thereafter until liver transplant
Secondary outcome [1] 345695 0
Immune function as measured by QUANTIFERON-Monitor assay
Timepoint [1] 345695 0
Baseline, 2 weeks, 4 weeks, then every 4 weeks thereafter until liver transplant
Day 1, 7, 14, 21 after liver transplant
Secondary outcome [2] 345696 0
Nutritional status measured by Subjective Global Assessment (SGA) tool
Timepoint [2] 345696 0
Baseline, 2 weeks, 4 weeks, then every 4 weeks thereafter until liver transplant
Day 7, 14, 21 after liver transplant
Secondary outcome [3] 345697 0
Anthropometry:: triceps skinfold measured by skinfold calipers, and mid-upper arm circumference measured with tape measure
Timepoint [3] 345697 0
Baseline, 2 weeks, 4 weeks, then every 4 weeks thereafter until liver transplant
Day 7, 14, 21 after liver transplant
Secondary outcome [4] 345698 0
Cross-sectional area of thigh muscle measured by ultrasound
Timepoint [4] 345698 0
Baseline, 2 weeks, 4 weeks, then every 4 weeks thereafter until liver transplant
Day 7, 14, 21 after liver transplant
Secondary outcome [5] 345699 0
Change in biochemistry (liver function tests, iron, vitamin B12, vitamin D, folate and zinc)
Timepoint [5] 345699 0
Baseline, 2 weeks, 4 weeks, then every 4 weeks thereafter until liver transplant
Day 7, 14, 21 after liver transplant
Secondary outcome [6] 345700 0
Metabolic rate measured by indirect calorimeter
Timepoint [6] 345700 0
Baseline, 2 weeks, 4 weeks, then every 4 weeks thereafter until liver transplant
Day 7, 14, 21 after liver transplant
Secondary outcome [7] 345701 0
Quality of liver measured by Chronic Liver Disease Questionnaire
Timepoint [7] 345701 0
Baseline, 1 month, 3 months, then every 3 months thereafter until liver transplant
1 month and 3 months after liver transplant
Secondary outcome [8] 345702 0
ICU length of stay following liver transplant, measured in hours. Outcome assessed by data-linkage to medical records (recorded in electronic medical record)
Timepoint [8] 345702 0
Recorded at time of discharge from ICU
Secondary outcome [9] 345703 0
Hospital length of stay following liver transplant, measured in days.
Outcome assessed by data-linkage to medical record.
Timepoint [9] 345703 0
Recorded at time of discharge from hospital
Secondary outcome [10] 345704 0
Duration of mechanical ventilation after liver transplant, measured in hours.
Outcome assessed by data-linkage to medical record (mechanical ventilation duration recorded in electronic medical record)
Timepoint [10] 345704 0
Recorded at time of ICU discharge
Secondary outcome [11] 345705 0
Duration of liver transplant surgery, measured in hours.
Outcome assessed by data-linkage to medical record (operative time recorded in electronic medical record)
Timepoint [11] 345705 0
Recorded following liver transplant
Secondary outcome [12] 345706 0
Volume of blood products administered during liver transplant surgery, measured in millilitres.
Outcome assessed by data-linkage to medical record
Timepoint [12] 345706 0
Recorded following liver transplant surgery
Secondary outcome [13] 345707 0
Prevalence of infection during hospital stay following liver transplant
Outcome assessed by data-linkage to medical record
Timepoint [13] 345707 0
Recorded at discharge from hospital
Secondary outcome [14] 345708 0
Presence of complications in the 90 days following liver transplant (rejection, biliary and wound complications, return to theatre)
Outcome assessed by data-linkage to medical record
Timepoint [14] 345708 0
Recorded at 90 days after transplant
Secondary outcome [15] 345709 0
Unplanned hospital readmission within 90 days of liver transplant
Outcome assessed by data-linkage to medical record
Timepoint [15] 345709 0
Recorded at 90 days after transplant
Secondary outcome [16] 345710 0
Liver graft survival at 90 days following liver transplant.
Outcome assessed by data-linkage to medical record
Timepoint [16] 345710 0
Recorded at 90 days after transplant
Secondary outcome [17] 345843 0
Patient survival at 90 days following liver transplant
Outcome assessed by data-linkage to medical record
Timepoint [17] 345843 0
Recorded at 90 days after transplant

Eligibility
Key inclusion criteria
All adult patients activated onto the liver transplant waiting list with:
- Diagnosis of severe malnutrition (SGA C)
- Handgrip strength below the sarcopenia cut-off for their age/sex
- Functional gastrointestinal tract
- MELD score >16
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants on the liver transplant waiting list will be excluded if they:
- Are well nourished (SGA A) or mild-moderately malnourished (SGA B)
- Are not sarcopenic as per handgrip strength cut off
- Without functioning gastrointestinal tract
- Have a low severity of liver disease (MELD <16)

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)
Computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
There are no previous clinical trials that have evaluated the impact of pre-transplant nasogastric feeding in malnourished patients on pre- or post-transplant outcomes, specifically functional muscle strength (handgrip strength). The sample size estimation is therefore based upon a recent clinical audit of patients with liver cirrhosis at Austin Health who received at least 4 weeks of nasogastric feeding in the community in an attempt to improve their nutritional and functional status. Mean grip strength ± SD was 20.9 ± 7.5 kg for the cohort at the commencement of feeding, increasing by 47% (median 43%) following an average of 3 months of nasogastric feeding. The expected effect size of the intervention for our trial is therefore conservatively estimated to be a 30% improvement in grip strength. At a power level of 0.8 and assuming a significance level of 0.05, an estimated sample size of 44 patients (22 in each group) will be required.

Repeated measures ANOVA will be used to evaluate changes in continuous data variables, including the primary outcome measure of change in hand grip strength. Categorical variables will be compared using Fisher’s exact test. Any variable identified as significant (p<0.05) in univariate analysis will be considered for multivariate analysis using multiple logistic regression models. Subgroup analysis by two-way repeated measures ANOVA will also be performed according to nutritional category against the main outcome variables. Cumulative overall survival rates will be calculated using Kaplan-Meier methods and differences between curves evaluated using the log-rank test. A two-tailed p value <0.05 will be considered statistically significant. All statistical analysis will be carried out by a statistician working with the research team, using current SPSS statistical software.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2018
Actual
19/10/2018
Date of last participant enrolment
Anticipated
31/12/2021
Actual
13/01/2023
Date of last data collection
Anticipated
31/03/2022
Actual
20/05/2023
Sample size
Target
50
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 10736 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 22459 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 299236 0
Charities/Societies/Foundations
Name [1] 299236 0
Austin Medical Research Foundation
Country [1] 299236 0
Australia
Funding source category [2] 302397 0
Commercial sector/Industry
Name [2] 302397 0
Novartis Pharmaceuticals Australia Pty Ltd
Country [2] 302397 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 298509 0
None
Name [1] 298509 0
Address [1] 298509 0
Country [1] 298509 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300159 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 300159 0
Ethics committee country [1] 300159 0
Australia
Date submitted for ethics approval [1] 300159 0
16/03/2018
Approval date [1] 300159 0
26/03/2018
Ethics approval number [1] 300159 0
HREC/18/Austin/43

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2600 2600 0 0
/AnzctrAttachments/374919-20180326 HREC18Austin43 April18 (Full Ethics Approval).pdf (Ethics approval)

Contacts
Principal investigator
Name 82734 0
A/Prof Adam Testro
Address 82734 0
Liver Transplant Unit
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country 82734 0
Australia
Phone 82734 0
+61394965353
Fax 82734 0
Email 82734 0
[email protected]
Contact person for public queries
Name 82735 0
Brooke Chapman
Address 82735 0
Nutrition and Dietetics Department
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country 82735 0
Australia
Phone 82735 0
+61394965011
Fax 82735 0
Email 82735 0
[email protected]
Contact person for scientific queries
Name 82736 0
Brooke Chapman
Address 82736 0
Nutrition and Dietetics Department
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country 82736 0
Australia
Phone 82736 0
+61394965011
Fax 82736 0
Email 82736 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not planning on publishing IPD


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseBody composition and the skeletal muscle compartment in liver transplantation: Turning challenges into opportunities.2022https://dx.doi.org/10.1111/ajt.17089
N.B. These documents automatically identified may not have been verified by the study sponsor.