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Trial registered on ANZCTR


Registration number
ACTRN12623001183673
Ethics application status
Approved
Date submitted
31/07/2023
Date registered
16/11/2023
Date last updated
27/10/2024
Date data sharing statement initially provided
16/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
IDEAL Care: Identifying Advanced Liver Fibrosis in Primary Care
Scientific title
A Multi-Centre Type 1 Hybrid Effectiveness Implementation Cluster Randomised Controlled Trial of an Integrated Liver Fibrosis Detection Pathway in Australian Primary Care
Secondary ID [1] 310218 0
None
Universal Trial Number (UTN)
Trial acronym
IDEAL Care (IDEntifying Advanced Liver fibrosis in primary CARE)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver Fibrosis 330900 0
Liver Disease 330901 0
Hepatocellular Carcinoma 330902 0
Liver Cirrhosis 330903 0
Liver Elastography 330904 0
Condition category
Condition code
Cancer 327685 327685 0 0
Liver
Oral and Gastrointestinal 327686 327686 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Public Health 327687 327687 0 0
Health service research
Public Health 327688 327688 0 0
Other public health

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
GP Education will be provided to both arms of the trial. Access to the education module will be provided by the research team at time of the site initiation with provision of hard copy and electronic versions and links available to the GPs within the practice.
Education material targeted towards GPs and eligible for RACGP Continuing Professional Development has recently been developed by CIs Leon Adams and Jon Emery. This will be provided to GPs in both arms before the pathway diverges. This will include a virtual or online educational module, a written summary and a clinical pathway with easy to interpret flow-diagrams regarding the identification of at-risk patients and the determination of advanced liver fibrosis. The intervention arm will also be provided with an overview of FHT and the trial intervention. We will evaluate the education module for acceptability and comprehensiveness before trial commencement via review by GP representatives on the steering committee. The outcomes will be used to make any modifications or additions to the education materials.

Prior to data collection, both control and intervention practices will have software installed (FHT and GRHANITE) to allow identification of the cohort at risk of chronic liver disease who fit the trial inclusion and exclusion criteria in both arms of the trial.
- FHT is a software platform which integrates into current GP practice management software which service greater than 90% of Australian practices. In relation to this trial, FHT will work as the ‘clinical decision support tool’ or ‘pop-up’ within the intervention practices.
- GRHANITE software will be installed in both control and intervention practices to enable extraction of de-identified data to the Patron dataset.
The FHT CDSS will be installed at consenting general practices for a maximum of 10 months, which will allow up to 4 months for patients to be identified by the CDSS and a further 6 months in order to account for the ascertainment of the primary outcome (newly diagnosed advanced liver fibrosis at 6 months post baseline appointment). FHT analytics will be captured within GRHANITE data surrounding CDSS data usage. Following randomisation, practices assigned to the intervention arm will have the FHT Clinical Decision Support System (CDSS) activated, this will consist of the following:
A) Patients fulfilling the at-risk identification criteria will have a FIB-4 score calculated by the FHT platform if the laboratory parameters (consisting of liver enzymes and platelet count) have been collected within the last 3 months. This 3-month time period will be calculated from the day of FHT activation. For any patients with a FIB-4 reported in the previous 3 months, an electronic report will be automatically generated. The reports will be delivered to GP inboxes for review, at which point the GP may determine that a patient should be recalled. It is anticipated that a large number of reports may be generated in some practices. To avoid creating administrative burden for the GP, the reports will be released in a staggered manner (e.g., 30 reports each week on Tuesday).
B) For any patients who are either (i) not actively recalled or (ii) do not have a historical FIB-4, GPs will be opportunistically alerted by the CDSS during a consultation from the electronic patient medical record if their patient is at-risk for advanced liver fibrosis and warrant further investigation.
During the first consultation, the FHT platform will prompt the GP to commence a two-stage fibrosis detection pathway consisting of; 1) a screening FIB-4 blood test (if no FIB-4 score has been calculated in the last 3 months) and 2) a diagnostic liver elastogram if indicated. Initially, if no FIB-4 score has been calculated in the last 3 months, the GP will be prompted to request a non-fasting, Medicare rebatable, platelet count and liver function test (ALT and AST) to facilitate the calculation of a FIB-4 score. Additional prompts will invite evaluation of current liver disease risk factors using drop-down boxes, reasons for not proceeding with the FIB-4 test if applicable, and a link to a printable patient information sheet regarding liver health, the rationale for the FIB-4 test and liver elastogram. Upon receipt of the laboratory results, a FIB-4 result will be automatically calculated by the FHT platform with a result provided to the GP for review within the electronic medical record (EMR) as part of their normal results workflow. Patients with a FIB-4 <1.3 have a 97% negative predictive value for advanced fibrosis and will not require further follow-up. It is anticipated that 30% of patients tested will have elevated scores (>=1.3) with increased risk of advanced liver fibrosis who will be recalled for review as per normal practice. Age adjusted cut-offs for FIB-4 will not be used due to the increased risk of false negative results.
During the 2nd consultation for patients with elevated FIB-4 scores (or the first consultation for those patients with FIB-4 scores already calculated in the last 3 months), the FHT platform will provide the GP with information to explain the result and rationale for a subsequent liver elastography if the screening FIB-4 is high (>=1.3) as well as a list of nearby recommended/preferred providers who offer scans with no out of pocket costs. Liver elastography referrals will be guided by the GP’s usual practice and the cost, wait time and location for the procedure will depend on the individual provider selected. It is anticipated 10-15 scans per month across Western Australia and Victoria will be required which is well within the capacity of elastography providers.
During a subsequent consultation (if required), the trial’s education content provided at baseline will provide a care pathway depending on the liver elastography result tailored to the type of elastography and etiology of liver disease using validated cut-offs predictive of advanced liver fibrosis which are also predictive of liver decompensation. Patients with advanced liver fibrosis, invalid or indeterminate elastography values (estimated to be 15-20% of those with a FIB-4 >=1.3) will be recommended for referral to a gastroenterologist/ hepatologist for further evaluation. These referrals will be captured as part of the medical record review during outcome evaluation.
Intervention code [1] 326604 0
Early detection / Screening
Comparator / control treatment
Usual Care Arm: Practices assigned to usual care will be provided education. The education module content will be the same across both intervention and control.
Control group
Active

Outcomes
Primary outcome [1] 335486 0
The difference in the proportion of patients identified with newly diagnosed advanced liver fibrosis among those aged 45-75 years visiting their GP during the study period with chronic liver disease risk factors present in the last 12 months in the intervention arm compared to the control arm.
Timepoint [1] 335486 0
6 months post-baseline GP appt.
Primary outcome [2] 336377 0
Cost-effectiveness of the fibrosis detection pathway versus usual care for costs associated with liver-related morbidity and mortality.
Timepoint [2] 336377 0
Measured at 6 months post-randomisation by calculating resource use and costs from MBS/PBS data.
Primary outcome [3] 336378 0
Individual-Level and Setting-Level Factors assessed in composite based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.
Timepoint [3] 336378 0
Measured during semi-structured qualitative interviews at baseline and at the end of the practice intervention period.
Quantitative data will be captured from the FHT/GRHANITE platforms for the intervention arm at 6 months post-randomisation. As well as from brief baseline, mid-point and end of trial surveys completed by practice nurses or managers.
Secondary outcome [1] 428094 0
Proportion of patients diagnosed with cirrhosis among those aged 45-75 years visiting their general practitioner (GP) during the study period.

This will be determined through following the IDEAL Care pathway inclusive of: FIB-4 tests, liver elastography results and input from hepatology/gastroenterology specialists. This data will be fully ascertained using the GRHANITE data extract in addition to the electronic medical record review.
Timepoint [1] 428094 0
At 6 months of follow-up after baseline patient visit.
Secondary outcome [2] 428095 0
Proportion of patients diagnosed with hepatocellular carcinoma Among those aged 45-75 years visiting their general practitioner (GP) during the study period.
This will be determined through following the IDEAL Care pathway inclusive of: FIB-4 tests, liver elastography results and input from hepatology/gastroenterology specialists. This data will be fully ascertained using the GRHANITE data extract in addition to the electronic medical record review.
Timepoint [2] 428095 0
At 6 months of follow-up after baseline patient visit.
Secondary outcome [3] 428096 0
Proportion of patients referred to specialist liver care among those aged 45-75 years visiting their general practitioner (GP) during the study period.

This will be determined through following the IDEAL Care pathway inclusive of: FIB-4 tests, liver elastography results and input from hepatology/gastroenterology specialists. This data will be fully ascertained using the GRHANITE data extract in addition to the electronic medical record review.
Timepoint [3] 428096 0
At 6 months of follow-up after baseline patient visit.

Eligibility
Key inclusion criteria
- Aged 45 to 75 years on the day prior to the patient’s baseline GP visit or day of GP review of historical FIB-4 is applicable, and one or more of the risk factors below
- Is an active patient at the GP practice
- Have had a minimum of one consultation with a GP during the trial intervention period OR- Patient has FIB-4 calculated (within 3 months of FHT activation) and the result is reviewed by the GP
- Have 1 or more risk factors for chronic liver disease, namely;
---Type 2 diabetes,
--- BMI of 30kg/m2 or terms for ‘obesity’ in addition to a metabolic risk factor (hypertension: BP greater than 130/85 or terms for ‘hypertension’ or active prescription of antihypertensive medication or dyslipidaemia: triglycerides greater than 150mg/dL (greater than 1.70 mmol/L) or HDL-cholesterol less than 40mg/dL (less than 1.0 mmol/L) for men and less than 50 mg/dL (less than 1.3 mmol/L) for women or has pre-diabetes [fasting blood glucose between 6.1-6.9 mmol/l or HbA1c between 6.0-6.4%])
- Elevated liver enzymes in previous 12 months defined as any of these:
---ALT: greater than 30 in men, greater than 19 in women IU/l,
---AST greater than 45 IU/l,

- Chronic viral hepatitis defined as any of these:
---Chronic hepatitis including chronic Hep B or, chronic Hep C (Positive HBsAg, HCV positive Ab)

- Chronic Fatty liver including steatohepatitis and non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD)

- Alcohol abuse and excess alcohol as determined from GP records or AUDIT score:
Equal to 3 for women,
Equal to 4 for men in the past 12 months
Minimum age
45 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients meeting any of the following criteria will be excluded from the trial:
- Existing diagnosis of cirrhosis, hepatocellular carcinoma, hepatic encephalopathy, ascites, or oesophageal varices.
- Pregnancy
- Residential Aged Care Facility (RACF) resident

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
To maintain allocation concealment, permuted block sizes will not be disclosed until the outcome measures have been ascertained for all practices. Following signed agreement by the GP practice and baseline measures completed by practices (eligibility confirmed, IT requirements met, practice contact details obtained), the GP practice information (unique identifier, name, postcode, rural vs urban practice and state) will be entered into REDcap and then will then be automatically randomly allocated to one of the two study arms. Randomisation will be implemented by the research assistant at the initial practice site visit. Unique codes will be used to mask the Identity of the practices when analysing the outcomes. Uninformative codes 1 and 2 will be used for the study arm allocation when the statistician generates the allocation schedule. Prior to starting randomising practices, the project co-ordinator will randomly allocate the intervention and control arms to one of the two uninformative codes. These codes will be stored securely until after the primary analysis has been completed and there has been a blinded review of the results.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Unit of randomisation will be the general practice (cluster). A statistician will computer-generate a 1:1 randomisation allocation schedule stratified by state (Victoria and WA) and general practice geographical location (rural vs urban according to MMM classifications), using permuted block sizes of random sizes within stratum to maintain balance between study arms. The allocation schedule will be uploaded by the lead statistician on the trial, CI Patty Chondros.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
For 85% power and 5% significance level (two-sided), 36 practices (17 practices in each arm), allowing for attrition of two practices with 8058 eligible patients for a minimum cluster size of 237 patients per practice are required to detect a between-arm difference of 3% in the primary endpoint (3.4% for intervention arm and 0.40% for control arm). We conservatively assumed 5% prevalence of undetected advanced liver fibrosis in the general practice population, of which 85% of patient who visit the intervention GP over the 12 months will have a FIB-4 test at point of care and 10% of patients will be sent for further investigations in the usual care arm. Further, we expect that 80% of patients will complete all the required investigations to confirm advanced liver fibrosis. We have also conservatively assumed an intra-cluster correlation (ICC) of 0.035 for the primary endpoint.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
27/09/2024
Actual
18/10/2024
Date of last participant enrolment
Anticipated
1/08/2025
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
36
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC

Funding & Sponsors
Funding source category [1] 314379 0
Government body
Name [1] 314379 0
Australian Government, Department of Health (Medical Research Future Fund)
Country [1] 314379 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
Office of ResearchResearch Finance35 Stirling Highway Perth WA 6009
Country
Australia
Secondary sponsor category [1] 316330 0
None
Name [1] 316330 0
Address [1] 316330 0
Country [1] 316330 0
Other collaborator category [1] 283170 0
University
Name [1] 283170 0
The University of Melbourne
Address [1] 283170 0
Country [1] 283170 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313472 0
The University of Western Australia
Ethics committee address [1] 313472 0
The University of Western Australia, 35 Stirling Highway, Crawley WA 6009
Ethics committee country [1] 313472 0
Australia
Date submitted for ethics approval [1] 313472 0
19/03/2024
Approval date [1] 313472 0
18/06/2024
Ethics approval number [1] 313472 0
2023/ET001136

Summary
Brief summary
This study aims to assess the effectiveness, cost-effectiveness, and implementation context of an integrated liver fibrosis detection pathway in detecting unrecognized advanced liver fibrosis in at-risk patients in primary care.

Who is it for?
You may be eligible to participate in this trial if you are between 45-75 years and are at risk of chronic liver disease and are under the care of a GP at a participating general practice clinic,

Study details
GP clinics will be randomised to one of two cluster groups. One group will receive usual care provided by their GP.
The other group will have a liver fibrosis detection pathway implemented through the Future Health Today (FHT) clinical decision support system (CDSS). GPs will be alerted by the CDSS from the electronic patient medical record if their patient is at-risk for advanced liver fibrosis and warrant further investigation. Further investigation will be prompted by way of a screening blood test for liver fibrosis and then a diagnostic special liver ultrasound, known as a liver elastogram.

It is hoped that this research will demonstrate if this clinical decision support system is effective in improving detection of liver disease and liver cancer, thus improving patient outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128286 0
Prof Leon Adams
Address 128286 0
The University of Western Australia (M503), 35 Stirling Highway,6009 Perth, WAAustralia
Country 128286 0
Australia
Phone 128286 0
+61 8 6151 0835
Fax 128286 0
Email 128286 0
[email protected]
Contact person for public queries
Name 128287 0
Ms Eliza Zmislja
Address 128287 0
Victorian Comprehensive Cancer CentreLevel 10, 305 Grattan St,3010 Parkville, VICAustralia
Country 128287 0
Australia
Phone 128287 0
+61 412142356
Fax 128287 0
Email 128287 0
[email protected]
Contact person for scientific queries
Name 128288 0
Ms Eliza Zmislja
Address 128288 0
Victorian Comprehensive Cancer CentreLevel 10, 305 Grattan St,3010 Parkville, VICAustralia
Country 128288 0
Australia
Phone 128288 0
+61 412142356
Fax 128288 0
Email 128288 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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19838Ethical approval    386307-(Uploaded-03-07-2024-10-15-24)-IDEAL HREC Approval 18June 2024.pdf
19839Study protocol    Study protocol will be available at a later date f... [More Details]



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.