Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000895886
Ethics application status
Approved
Date submitted
4/03/2021
Date registered
8/07/2021
Date last updated
8/07/2021
Date data sharing statement initially provided
8/07/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Heart dysfunction in patients with liver cirrhosis
Scientific title
Evaluation for cirrhotic cardiomyopathy: A prospective study of global cardiac function in decompensated cirrhosis and its clinical significance
Secondary ID [1] 303599 0
nil known
Universal Trial Number (UTN)
Trial acronym
CCM study
Linked study record
nil

Health condition
Health condition(s) or problem(s) studied:
cirrhosis 320969 0
cirrhotic cardiomyopathy 320970 0
hepatorenal syndrome 320971 0
Condition category
Condition code
Cardiovascular 319385 319385 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
Each patient will have their blood tests for troponin and BNP added to their reguaklr blood tests. They will receive an appointment for Electrocardiogram, Transthoracic echocardiogram and dobutamine stress echocardiogram which will approximately take 40-50 minutes. This will be performed by a senior echocardiographer under the supervision of a cardiologist in the cardiology investigation suite.
Patients will be followed up for the next 12 months using the elctronic medical records. Those who undergo liver transplantation will undergo a repeat echocardiogram 12 months after their trasnplantation
Intervention code [1] 319884 0
Diagnosis / Prognosis
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326723 0
Define prevalence of CCM using Global Longitudinal strain (GLS) and Global myocardial work Index (GWI) at rest and under pharmacological stress if required
Timepoint [1] 326723 0
12 months from the time of inclusion
Primary outcome [2] 327249 0
Composite outcome: Disease severity assessed by MELD score, aetiology of liver disease and the development of a number of specific complications of cirrhosis such refractory ascites and development of HRS, cardiac failure, and death.
Timepoint [2] 327249 0
12 months from the time of study recruitment
Primary outcome [3] 327250 0

Define critical threshold of GLS/GWI in patients with CCM using transthoracic echocardiography and dobutamine stress echocardiography
Timepoint [3] 327250 0
12 months from study recruitment
Secondary outcome [1] 392470 0
Composite outcome: Assess levels of troponin T and brain-natriuretic peptide using serum samples
Timepoint [1] 392470 0
Within 12 months of recruitment and liver transplantation
Secondary outcome [2] 397939 0
Echocardiographic assessment post-transplant for CCM
Timepoint [2] 397939 0
Within 12 months of recruitment and liver transplantation

Eligibility
Key inclusion criteria
1.Consecutive consenting cirrhotic patients with ascites and or past history of ascites on diuretics including
a) those requiring abdominal paracentesis,
b) hydrothorax requiring thoracentesis,
c) planned for TIPS.
2. Consecutive cirrhotic patients undergoing LT assessment with or without ascites.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.ongoing sepsis on inotropes;
2. ongoing grade 2–4 hepatic encephalopathy;
3. known coronary artery disease;
4. other known cardiac diagnoses such as valvular heart disease, dilated, hypertrophic and restrictive cardiomyopathy
5. Uncontrolled systemic hypertension
5. Contraindications to dobutamine, including:
o Previous sensitivity to dobutamine
o Previous documented Ventricular Tachycardia or Ventricular Fibrillation

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Results will be reported as frequencies or means + standard deviation (SD) plus 95% confidence interval (CI) of the mean. Student t, Mann-Witney’s, and chi-squared tests will be used to compare groups for continuous and categorical variables, respectively. The diagnostic accuracy of GLS and GWI in predicting HRS and survival at 12 months will be assessed using the receiver-operating-curve and C-statistic. Echocardiographic parameters will be compared between baseline and post stress test using either paired t-test or the sign-rank test. A Kaplan-Meier analysis will be used to estimate survival probability and the curves will be compared by the log-rank test. Multivariate analysis Cox regression analysis that allows for multiple failure types will be used to identify variables associated with adverse clinical outcomes. We will also estimate the cumulative incidence of morbidity and mortality according to CCM status using competing risks models. Analysis will be performed using Stata (version 16.0).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
13/01/2021
Date of last participant enrolment
Anticipated
15/01/2023
Actual
Date of last data collection
Anticipated
15/01/2024
Actual
Sample size
Target
80
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 18848 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 18849 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 33347 0
5042 - Bedford Park
Recruitment postcode(s) [2] 33348 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 308020 0
University
Name [1] 308020 0
Flinders University
Country [1] 308020 0
Australia
Primary sponsor type
Hospital
Name
Flinders Medical Centre
Address
Flinders drive
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 308742 0
None
Name [1] 308742 0
Address [1] 308742 0
Country [1] 308742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308010 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 308010 0

Ward 6C, Room 6A219
Flinders Drive, Bedford Park SA 5042
Ethics committee country [1] 308010 0
Australia
Date submitted for ethics approval [1] 308010 0
23/11/2020
Approval date [1] 308010 0
17/12/2020
Ethics approval number [1] 308010 0
HREC/20/SAC/211

Summary
Brief summary
Cirrhotic cardiomyopathy (CCM) is a specific type of cardiac dysfunction seen in liver cirrhosis without a primary cardiac cause. It is an important cause of morbidity and mortality before and after liver transplantation (LT).
Despite its high prevalence, it is relatively understudied as the diagnosis often becomes clearer only under stressful conditions. The study aims to define early diagnosis of cirrhotic cardiomyopathy using advanced echocardiographic techniques and its clinical significance. In addition, the reversibility of cardiac dysfunction thus studied, will be assessed after LT. In a cohort of 80 consecutive cirrhotic patients, this will evaluate global myocardial work index (GWI)and global longitudinal strain (GLS) as markers of CCM under resting conditions and under pharmacologically induced stress when necessary. The study cohort will be followed-up for 12 months with respect to development of complications such as renal dysfunction, fluid overload, cardiac failure and death/ Lliver transplantation. It will provide the first ever description of GWI and GLS in the diagnosis of CCM in decompensated cirrhosis and its clinical correlation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109222 0
Dr JEYAMANI RAMACHANDRAN
Address 109222 0
Hepatology and Liver Transplantation Unit, Department of Gastroenterology and Hepatology, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042.
Senior researcher
College of Medicine and Public Health
Flinders University
Flinders drive, Bedford Park South Australia 5042
GPO Box 2100 Adelaide SA 5001
Country 109222 0
Australia
Phone 109222 0
+61456317486
Fax 109222 0
Email 109222 0
jeyamani.ramachandran@flinders.edu.au
Contact person for public queries
Name 109223 0
Dr Jeyamani Ramachandran
Address 109223 0
Senior researcher
College of Medicine and Public Health
Flinders University
Flinders drive, Bedford Park South Australia 5042
GPO Box 2100 Adelaide SA 5001
Country 109223 0
Australia
Phone 109223 0
+61456317486
Fax 109223 0
Email 109223 0
jeyamani.ramachandran@flinders.edu.au
Contact person for scientific queries
Name 109224 0
Dr Jeyamani Ramachandran
Address 109224 0
Senior researcher
College of Medicine and Public Health
Flinders University
Flinders drive, Bedford Park South Australia 5042
GPO Box 2100 Adelaide SA 5001
Country 109224 0
Australia
Phone 109224 0
+61456317486
Fax 109224 0
Email 109224 0
jeyamani.ramachandran@flinders.edu.au

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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10882Study protocolstudy protocol   381541-(Uploaded-04-03-2021-12-13-54)-Study-related document.docx
10883Ethical approvalethics approval   381541-(Uploaded-04-03-2021-12-06-40)-Study-related document.pdf
10884Informed consent formpatient information form   381541-(Uploaded-04-03-2021-12-06-40)-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.