ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

CRICC

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Liver cirrhosis

Cirrhotic Cardiomyopathy

Liver Transplantation

Condition category

Condition code

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Cardiovascular

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]

Early Detection / Screening

Intervention code [2]

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]

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]

30 days post transplant.

Primary outcome [2]

Resolution of cirrhotic cardiomyopathy post liver transplantation.

Timepoint [2]

3 months post liver transplantation.

Primary outcome [3]

Change of microvascular function post liver transplantation as assessed by the dynamic vessel analyser (DVA).

Timepoint [3]

3 months post liver transplant.

Secondary outcome [1]

All-cause death.

Timepoint [1]

At 1 year and at maximal achieved follow up.

Secondary outcome [2]

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]

30-day and 1 year.

Secondary outcome [3]

Degree of microvascular dysfuction in patient with diagnosed cirrhotic cardiomyopathy (CCM) compared to cirrhotic patients awaiting liver transplantation without CCM.

Timepoint [3]

Patients ill be assessed at time of wait-listing for liver transplantation.

Secondary outcome [4]

Investigation for an association between cirrhotic cardiomyopathy and elevated inflammatory biomarkers on pre-transplant screening pathology tests.

Timepoint [4]

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?

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

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Heidelberg

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Austin Medical Research Foundation

Address [1]

Country [1]

Australia

Primary sponsor type

Government body

Name

National Health and Medical Reasearch Council (NHMRC) - Post graduate scholarship

Address

Country

Australia

Secondary sponsor category [1]

Charities/Societies/Foundations

Name [1]

National Heart Foundation (NHF) - Post graduate scholarship

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

https://www.austin.org.au/Office-for-Research/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

25/10/2023

Approval date [1]

07/12/2023

Ethics approval number [1]

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

Prof Omar Farouque

Address

Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084

Country

Australia

Phone

+61 394963034

Fax

[email protected]

Contact person for public queries

Name

Dr Anoop Koshy

Address

Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084

Country

Australia

Phone

+61432661842

Fax

[email protected]

Contact person for scientific queries

Name

Dr Anoop Koshy

Address

Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084

Country

Australia

Phone

+61432661842

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Preservation of patient confidentiality.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
21670	Informed consent form					387353-(Uploaded-16-02-2024-16-09-50)-Study-related document.docx
21671	Ethical 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.

Trial Review

Documents added manually

Documents added automatically