ANZCTR - Registration

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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]

nil known

Universal Trial Number (UTN)

Trial acronym

CCM study

Linked study record

nil

Health condition

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

cirrhosis

cirrhotic cardiomyopathy

hepatorenal syndrome

Condition category

Condition code

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

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]

Diagnosis / Prognosis

Comparator / control treatment

no control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

12 months from the time of inclusion

Primary outcome [2]

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]

12 months from the time of study recruitment

Primary outcome [3]

Define critical threshold of GLS/GWI in patients with CCM using transthoracic echocardiography and dobutamine stress echocardiography

Timepoint [3]

12 months from study recruitment

Secondary outcome [1]

Composite outcome: Assess levels of troponin T and brain-natriuretic peptide using serum samples

Timepoint [1]

Within 12 months of recruitment and liver transplantation

Secondary outcome [2]

Echocardiographic assessment post-transplant for CCM

Timepoint [2]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Flinders Medical Centre - Bedford Park

Recruitment hospital [2]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment postcode(s) [1]

5042 - Bedford Park

Recruitment postcode(s) [2]

5112 - Elizabeth Vale

Funding & Sponsors

Funding source category [1]

University

Name [1]

Flinders University

Address [1]

Flinders Drive, Bedford Park, SA 5042

Country [1]

Australia

Primary sponsor type

Hospital

Name

Flinders Medical Centre

Address

Flinders drive
Bedford Park
SA 5042

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee

Ethics committee address [1]


Ward 6C, Room 6A219
Flinders Drive, Bedford Park SA 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/11/2020

Approval date [1]

17/12/2020

Ethics approval number [1]

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

Dr JEYAMANI RAMACHANDRAN

Address

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

Australia

Phone

+61456317486

Fax

[email protected]

Contact person for public queries

Name

Jeyamani Ramachandran

Address

Senior researcher
College of Medicine and Public Health
Flinders University
Flinders drive, Bedford Park South Australia 5042
GPO Box 2100 Adelaide SA 5001

Country

Australia

Phone

+61456317486

Fax

[email protected]

Contact person for scientific queries

Name

Jeyamani Ramachandran

Address

Senior researcher
College of Medicine and Public Health
Flinders University
Flinders drive, Bedford Park South Australia 5042
GPO Box 2100 Adelaide SA 5001

Country

Australia

Phone

+61456317486

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

for ethics and confidentiality reasons

What supporting documents are/will be available?

Doc. No.	Type	Citation	Attachment
10882	Study protocol	study protocol	381541-(Uploaded-04-03-2021-12-13-54)-Study-related document.docx
10883	Ethical approval	ethics approval	381541-(Uploaded-04-03-2021-12-06-40)-Study-related document.pdf
10884	Informed consent form	patient 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.

Trial Review

Documents added manually

Documents added automatically