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Trial registered on ANZCTR


Registration number
ACTRN12624000321549
Ethics application status
Approved
Date submitted
21/02/2024
Date registered
25/03/2024
Date last updated
14/07/2024
Date data sharing statement initially provided
25/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Cardiovascular Risk in Cirrhotic Cardiomyopathy (CRICC) - Evaluation of Cardiovascular Risk Prediction in Patients Undergoing Liver Transplantation
Scientific title
Cirrhotic Cardiomyopathy and Evaluation of Cardiovascular Risk Prediction in Patients Undergoing Liver Transplantation
Secondary ID [1] 311558 0
None
Universal Trial Number (UTN)
Trial acronym
CRICC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver cirrhosis 332921 0
Cirrhotic Cardiomyopathy 332922 0
Liver Transplantation 332923 0
Condition category
Condition code
Oral and Gastrointestinal 329634 329634 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cardiovascular 329635 329635 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
There are no medical interventions in this trial, just additional medical tests.

Patients will undergo a follow up dobutamine stress echocardiogram (DSE) (a cardiac stress test that is routinely performed in the liver transplant workup period) to assess for resolution of the changes that are proposed to be associated with cirrhotic cardiomyopathy. This test takes approximately 30 minutes and will be performed at the Austin Hospital Cardiology department in Heidelberg Victoria. The test will be performed approximately 3 months post liver transplantation. Pathology samples will be taken and stored during both pre-operative and post-operative DSEs during the cannulation that is required for the test.

Patients will also undergo a non-invasive assessment of their retinal vasculature using the dynamic vessel analyser camera. This process takes approximately 20-30 minutes and will be performed at the Austin Hospital in Heidelberg Victoria by a trained orthoptist. This will assess the patient's microvascular function which will then be correlated with their post-transplant outcomes. Patients will then have repeat testing approximately 3 months post liver transplantation.
Intervention code [1] 328010 0
Early Detection / Screening
Intervention code [2] 328011 0
Diagnosis / Prognosis
Comparator / control treatment
This is not a randomised control trial and as such there will be no formal control group. However, patients with cirrhotic cardiomyopathy will be compared against a control group of cirrhotic patients without evidence of cirrhotic cardiomyopathy with regards to their test results and post-transplant outcomes. This control group will still receive normal treatment as per standard of care. Standard of care is based on the protocols of the Victorian Liver Transplant Unit at Austin Health and involves a detailed assessment of cardiac risk prior to liver transplantation, as guided by the patient's underlying cardiovascular risk factors. Microvascular function of cirrhotic patients as assessed by the dynamic vessel analyser camera will be compared against that of a group of healthy controls.
Control group
Active

Outcomes
Primary outcome [1] 337420 0
30-day post-operative major adverse cardiovascular events (MACE) or death. MACE is defined as any episodes of acute coronary syndrome, ventricular arrhythmia, cardiac arrest or exacerbation of heart failure.
Timepoint [1] 337420 0
30 days post transplant.
Primary outcome [2] 337421 0
Resolution of cirrhotic cardiomyopathy post liver transplantation.
Timepoint [2] 337421 0
3 months post liver transplantation.
Primary outcome [3] 337422 0
Change of microvascular function post liver transplantation as assessed by the dynamic vessel analyser (DVA).
Timepoint [3] 337422 0
3 months post liver transplant.
Secondary outcome [1] 431807 0
All-cause death.
Timepoint [1] 431807 0
At 1 year and at maximal achieved follow up.
Secondary outcome [2] 431808 0
Major adverse cardiovascular events (MACE), both collectively and the individual constituent cardiac events which form the MACE end-point (cardiac arrest, acute myocardial infarction, heart failure and ventricular arrhythmias).
Timepoint [2] 431808 0
30-day and 1 year.
Secondary outcome [3] 431809 0
Degree of microvascular dysfuction in patient with diagnosed cirrhotic cardiomyopathy (CCM) compared to cirrhotic patients awaiting liver transplantation without CCM.
Timepoint [3] 431809 0
Patients ill be assessed at time of wait-listing for liver transplantation.
Secondary outcome [4] 431810 0
Investigation for an association between cirrhotic cardiomyopathy and elevated inflammatory biomarkers on pre-transplant screening pathology tests.
Timepoint [4] 431810 0
At the time of dobutamine stress echocardiography.

Eligibility
Key inclusion criteria
The study population for all study arms will be drawn from the Victorian Liver Transplant Unit at Austin Health, the state-wide service and adult liver transplant centre for Victoria and Tasmania. We will aim to prospectively recruit all adult patients (>18 years) who are waitlisted for transplantation and/or undergo pre-operative dobutamine stress echocardiography as part of their cardiac assessment as per usual unit protocols.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
During dobutamine stress echocardiography, patients who develop chest pain, significant ST segment changes or regional wall motion abnormalities during stress will be excluded.

Patients with overt heart failure, significant valvular disease, pulmonary hypertension, amyloidosis, haemochromatosis and those on renal replacement therapy will also be excluded.

Finally, patients will be excluded if an adequate retinal examination is not possible due to cataracts or narrow-angle glaucoma.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
Informed by annual transplant data, we estimate a total of 150-200 patients will be waitlisted for transplant over a 2 year time period, with an estimated 140-160 patients successfully proceeding to liver transplantation.

Based on our previously published studies evaluating prediction of post-transplant cardiovascular events, we anticipate that inclusion of 121 patients will provide robust statistical power to detect an association between cirrhotic cardiomyopathy and major adverse cardiovascular outcomes at an alpha of 0.05 and 90% power. We will therefore recruit 150 patients to allow for a 15% rate of delisting or mortality on the transplant waiting list.

Given the ~40% prevalence of impaired cardiac reserve in this population, approximately 50 patients will be recruited for repeat dobutamine stress echocardiography following liver transplantation to assess for reversibility of this condition.

Patients will be recruited at time of waitlisting for liver transplantation and as part of the referral process for dobutamine echocardiography for pre-operative cardiovascular risk factor assessment.

Statistical analyses for all studies will be performed using STATA-17. Baseline characteristics will be summarized using descriptive statistics. Continuous variables will be described as mean and standard deviation and be compared using Student’s t test. Categorical variables will be described as frequencies and percentages and compared using Fisher’s exact or chi-square tests as appropriate. We will define significance as achieving a p-value of <0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
25/03/2024
Actual
25/03/2024
Date of last participant enrolment
Anticipated
29/12/2025
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
200
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26186 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 42059 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 315855 0
Charities/Societies/Foundations
Name [1] 315855 0
Austin Medical Research Foundation
Country [1] 315855 0
Australia
Primary sponsor type
Government body
Name
National Health and Medical Reasearch Council (NHMRC) - Post graduate scholarship
Address
Country
Australia
Secondary sponsor category [1] 317991 0
Charities/Societies/Foundations
Name [1] 317991 0
National Heart Foundation (NHF) - Post graduate scholarship
Address [1] 317991 0
Country [1] 317991 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314889 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 314889 0
https://www.austin.org.au/Office-for-Research/
Ethics committee country [1] 314889 0
Australia
Date submitted for ethics approval [1] 314889 0
25/10/2023
Approval date [1] 314889 0
07/12/2023
Ethics approval number [1] 314889 0

Summary
Brief summary
Liver transplantation offers a cure for Australians with end-stage liver failure. Cardiovascular disease remains a leading cause of death following this procedure, with rates of post-transplant cardiac events remaining high over the past 20 years despite improvements in overall complication rates. This may be due to undetected cardiac dysfunction, termed cirrhotic cardiomyopathy, however our ability to diagnose and treat this condition in clinical practice remains limited.

Using a novel, validated method for identifying this condition using stress testing, we aim to evaluate whether cirrhotic cardiomyopathy increases the risk of post-transplant cardiovascular events, and determine whether liver transplantation leads to a reversal of this condition. Based on the outcome of this study, the long-term goal is to assess whether use of early treatments in patients with cirrhotic cardiomyopathy can reduce the risk of post-transplant cardiovascular events and improve patient outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132470 0
Prof Omar Farouque
Address 132470 0
Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084
Country 132470 0
Australia
Phone 132470 0
+61 394963034
Fax 132470 0
Email 132470 0
[email protected]
Contact person for public queries
Name 132471 0
Dr Anoop Koshy
Address 132471 0
Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084
Country 132471 0
Australia
Phone 132471 0
+61432661842
Fax 132471 0
Email 132471 0
[email protected]
Contact person for scientific queries
Name 132472 0
Dr Anoop Koshy
Address 132472 0
Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084
Country 132472 0
Australia
Phone 132472 0
+61432661842
Fax 132472 0
Email 132472 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
Preservation of patient confidentiality.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21670Informed consent form    387353-(Uploaded-16-02-2024-16-09-50)-Study-related document.docx
21671Ethical approval    387353-(Uploaded-16-02-2024-16-10-34)-Study-related document.docx



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.