Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001166561
Ethics application status
Approved
Date submitted
4/09/2024
Date registered
25/09/2024
Date last updated
25/09/2024
Date data sharing statement initially provided
25/09/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Metabolomic Profiling and Cardiovascular Outcomes in Patients with Cirrhotic Cardiomyopathy Undergoing Liver Transplantation
Scientific title
Metabolomic Profiling and Cardiovascular Outcomes in Patients with Cirrhotic Cardiomyopathy Undergoing Liver Transplantation
Secondary ID [1] 312901 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cirrhotic cardiomyopathy 335055 0
Liver transplantation 335111 0
Cirrhosis 335112 0
Condition category
Condition code
Oral and Gastrointestinal 331565 331565 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cardiovascular 331566 331566 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The are no medical interventions in this trial. All patients will be undergoing tests as part of their standard assessment for liver transplantation. Some additional tests may be required as part of the trial.

Patients will undergo a blood collection to be used for metabolomic analysis. This will be done, where possible, during the same venepuncture as their standard liver transplant pathology collection. Blood collection will be repeated at 6 months post liver transplantation. Again, where possible, this will be done coinciding with pathology required for routine clinical care. .

Patients will undergo dobutamine stress echocardiography (DSE) prior to liver transplantation, to aid in diagnosis of cardiac dysfunction, in particular contractile reserve and stress diastology. DSEs are performed in many patients as a standard part of a liver transplant work up, but will be performed in all patients as part of this trial. Patients with abnormalities consistent with cirrhotic cardiomyopathy on their pre-transplant DSE will undergo a post-transplant DSE at 6 months after transplant, to assess for reversibility of these changes. The test takes 30 minutes and will be performed at The Royal Prince Alfred Cardiology Department in Camperdown, NSW.
Intervention code [1] 329438 0
Diagnosis / Prognosis
Intervention code [2] 329475 0
Early Detection / Screening
Comparator / control treatment
There will be no formal control group as this is not a randomised controlled trial. Patients with cirrhotic cardiomyopathy will be compared with patients without cirrhotic cardiomyopathy, who have undergone the same testing as part of standard of care, based on the cardiovascular assessment protocol of the Australian National Liver Transplant Unit at the Royal Prince Alfred Hospital.
Control group
Active

Outcomes
Primary outcome [1] 339303 0
The accuracy of diagnosis of cirrhotic cardiomyopathy using metabolomic profiling
Timepoint [1] 339303 0
Bloods for metabolomics, TTE and DSE will be performed pre-transplant within 6 months of listing, and at 6 months post-transplant.
Primary outcome [2] 339304 0
12 month major adverse cardiovascular events (MACE). MACE is defined as new episodes of atrial or ventricular arrhythmia, heart failure, stroke, pulmonary embolism cardiac arrest or cardiac death.
Timepoint [2] 339304 0
12 months post-transplant
Primary outcome [3] 339347 0
Changes in the metabolomic profile of patients with cirrhotic cardiomyopathy after liver transplantation
Timepoint [3] 339347 0
Bloods for metabolomics will be collected pre-transplant within 6 months of listing, and at 6 months post-liver transplantation
Secondary outcome [1] 439399 0
Resolution of changes associated with cirrhotic cardiomyopathy on DSE post-transplantation
Timepoint [1] 439399 0
6 months post transplant
Secondary outcome [2] 439400 0
Accuracy of pre-transplant brain natriuretic peptide in predicting major adverse cardiovascular events post transplant
Timepoint [2] 439400 0
BNP levels will be collected pre-transplant within 6 months of listing, and correlated with major adverse cardiac events at 12 months post-transplant
Secondary outcome [3] 439609 0
Levels of von-Willebrand factor antigen in cirrhotic cardiomyopathy
Timepoint [3] 439609 0
VWF antigen activity and echocardiography for diagnosis of cirrhotic cardiomyopathy will be performed pre-transplant within 6 months of listing

Eligibility
Key inclusion criteria
Patients undergoing assessment for liver transplantation at the Australian National Liver Transplant Unit at The Royal Prince Alfred Hospital will be prospectively recruited
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Patients with non-cirrhotic indications for liver transplant
2) Patients undergoing multi-organ transplantation
3) Patients with haemodynamically significant valvular heart disease, non-revascularised coronary artery disease, or any pre-existing non-cirrhotic cardiomyopathy
4) Patients with underlying liver diseases that can potentially cause infilitrative cardiovascular disease such as amyloidosis, sarcodosis, or haemochromotosis

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We are aiming for recruitment of 100-150 patients over a three year period.

Statistical analysis will be performed using R Statistical Software. Baseline characteristics will be summarised using descriptive statistics, with continuous variables described as mean and standard deviation if normally distributed, or median and interquartile range if skewed and compared using independent t-test or Mann Whitney U Test. Categorical variables will be described as frequencies and percentages and compared using chi-square tests. Linear and logistic regression modelling will be used to define predictors for outcomes. Survival analysis will be performed using Kaplan-Maier plots and cox proportional hazard models and log-rank tests.

Metabolite levels will be scaled to standardize the variance in metabolite concentrations and be presented as fold changes. Principal component analysis (PCA) will be used to reduce the dimensions of the data to allow for comparison of variation between patient groups. Univariate and multivariate linear and logistic regression models will be used to examine the association between metabolites levels and clinical parameters and subgroups. For regression analyses, the Benjamini-Hochberg procedure will be used to control the false-discovery rate for multiple comparisons. Pathway analyses will be performed using publicly available platforms.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
3/03/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
150
Accrual to date
105
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27078 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 43145 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 317335 0
Charities/Societies/Foundations
Name [1] 317335 0
Gastroenterological Society of Australia
Country [1] 317335 0
Australia
Funding source category [2] 317336 0
Charities/Societies/Foundations
Name [2] 317336 0
Royal Australian College of Physicians
Country [2] 317336 0
Australia
Funding source category [3] 317446 0
Government body
Name [3] 317446 0
National Health and Medcial Research Council Postgraduate Scholarship
Country [3] 317446 0
Australia
Primary sponsor type
Individual
Name
Dr Madeleine Gill
Address
Country
Australia
Secondary sponsor category [1] 319619 0
Hospital
Name [1] 319619 0
The Royal Prince Alfred Hospital
Address [1] 319619 0
Country [1] 319619 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316066 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 316066 0
Ethics committee country [1] 316066 0
Australia
Date submitted for ethics approval [1] 316066 0
20/10/2021
Approval date [1] 316066 0
23/11/2021
Ethics approval number [1] 316066 0
X21-0376 & 2021/ETH11793

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136666 0
Dr Madeleine Gill
Address 136666 0
Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, 2050, NSW
Country 136666 0
Australia
Phone 136666 0
+61 2 9515 8839
Fax 136666 0
Email 136666 0
madeleine.gill@health.nsw.gov.au
Contact person for public queries
Name 136667 0
Dr Madeleine Gill
Address 136667 0
Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, 2050, NSW
Country 136667 0
Australia
Phone 136667 0
+61 2 9515 8839
Fax 136667 0
Email 136667 0
madeleine.gill@health.nsw.gov.au
Contact person for scientific queries
Name 136668 0
Dr Madeleine Gill
Address 136668 0
Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, 2050, NSW
Country 136668 0
Australia
Phone 136668 0
+61 2 9515 8839
Fax 136668 0
Email 136668 0
madeleine.gill@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24160Informed consent form    388402-(Uploaded-04-09-2024-14-45-33)-CCM Study Consent Form.pdf
24161Ethical approval    388402-(Uploaded-04-09-2024-14-46-03)-2021_STE04295 - Ethics approval letter dated.pdf



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.