Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001183673p
Ethics application status
Submitted, not yet approved
Date submitted
31/07/2023
Date registered
16/11/2023
Date last updated
16/11/2023
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
IDEAL Care Trial: A Multi-Centre Type 1 Hybrid Effectiveness Implementation Cluster Randomised Controlled Trial of an Integrated Liver Fibrosis Detection Pathway for patients aged 45-75 years with risk factor(s) for chronic liver disease 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
Education material, including a video, will be provided to GPs on identifying and managing advanced liver fibrosis. The video will be shown during consent form signing and recruitment, along with links to additional resources. GPs in both arms will receive a written summary and clinical pathway with flow-diagrams for identifying at-risk patients and advanced liver fibrosis.
The intervention arm will also receive information about Future Health Today and how the clinical decision support tool works. This will be provided to GPs in a ‘how to’ video to show GPs as well as an FHT module instruction manual provided to the general practices within the intervention arm.
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 prior to the baseline patient visit for historical FIB-4 scores (FHT calculations are performed in practices overnight on a daily basis).
B) GPs will be opportunistically alerted by the FHT CDSS during a consultation from the electronic patient medical record if their patient is at-risk for advanced liver fibrosis and warrant further investigation. The anticipated time GPs will spend interacting with the platform will differ across patients. This will depend on whether the patients medical record has triggered the pop-up due to historical pathology tests triggering a FIB-4 calculation, the FIB-4 score and the patients’ engagement and health literacy.
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) 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. Liver elastography is performed using an ultrasound probe and is painless, this non-invasive test is used to measure liver health by way of measuring liver stiffness.
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 greater than 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 (greater than or equal to 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 second 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 (greater than or equal to 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 greater than or equal to 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.

Data will also be extracted from the FHT platform using a remote and automated process. This data encapsulates de-identified usage data for each practice (including number of active FHT users, number of times a component of FHT is activated, number of times an algorithm is activated, number of times an algorithm is deferred and why, age and gender profile of patients). There is no identifiable data contained in the extracted data. Usage data will also be used to evaluate time spent on the FHT platform.
Intervention code [1] 326604 0
Early detection / Screening
Comparator / control treatment
Usual Care Arm: Practices assigned to usual care will be provided education.

Education material, including a video, will be provided to GPs on identifying and managing advanced liver fibrosis. The video will be shown during consent form signing and recruitment, along with links to additional resources. GPs in both arms will receive a written summary and clinical pathway with flow-diagrams for identifying at-risk patients and advanced liver fibrosis.

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 >90% of Australian practices. GRHANITE software will be installed in both control and intervention practices to enable extraction of de-identified data to the Patron dataset. however the FHT clinical decision support tool will be inactive in these clinics.

Patients will be managed by their GP according to usual practice.
Control group
Active

Outcomes
Primary outcome [1] 335486 0
Proportion of patients identified with newly diagnosed advanced liver fibrosis among those aged 45-75 years visiting their general practitioner (GP) during the study period with chronic liver disease risk factor(s).

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] 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 linked state-based administrative datasets and 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 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
- 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)
Allocation will be concealed using a randomisation module embedded in the online database. Within the online database, each record (practice) will have 2 check boxes for the researcher to confirm both stratum were entered/calculated correctly in baseline (clinic and AUDIT) prior to the researcher clicking a button labelled ‘randomise’. No record can proceed without randomisation via this method. Next steps for the participant will be outlined on the screen after the randomise button is clicked (i.e. usual care will instruct researcher to thank participant for their time and remind them that software will still be installed and patient data will still be extracted in order to provided study analysis, Intervention will instruct researcher to explain that participation will mean the FHT CDSS will be switched on post software installation. This cannot be undone or changed. After the record has been randomised, it will be included in intention to treat analysis. No record can be randomised more than once.
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), 34 practices (17 practices in each arm) 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
Not yet recruiting
Date of first participant enrolment
Anticipated
4/12/2023
Actual
Date of last participant enrolment
Anticipated
30/09/2024
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
34
Accrual to date
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

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313472 0
University of Melbourne, Human Research Ethics Committee
Ethics committee address [1] 313472 0
Office of Research Ethics & IntegrityLevel 5, 161 Barry StreetThe University of MelbourneVIC 3010
Ethics committee country [1] 313472 0
Australia
Date submitted for ethics approval [1] 313472 0
01/11/2023
Approval date [1] 313472 0
Ethics approval number [1] 313472 0

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 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. 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
leon.adams@uwa.edu.au
Contact person for public queries
Name 128287 0
Ms Rachel Brooks
Address 128287 0
Victorian Comprehensive Cancer CentreLevel 10, 305 Grattan St,3010 Parkville, VICAustralia
Country 128287 0
Australia
Phone 128287 0
+61450400112
Fax 128287 0
Email 128287 0
brooks.r@unimelb.edu.au
Contact person for scientific queries
Name 128288 0
Ms Rachel Brooks
Address 128288 0
Victorian Comprehensive Cancer CentreLevel 10, 305 Grattan St,3010 Parkville, VICAustralia
Country 128288 0
Australia
Phone 128288 0
+61450400112
Fax 128288 0
Email 128288 0
brooks.r@unimelb.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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19838Ethical approval    Ethical approval will be available at a later date... [More Details]
19839Study protocol    Study protocol will be available at a later date f... [More Details]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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