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Trial registered on ANZCTR


Registration number
ACTRN12620000158965
Ethics application status
Approved
Date submitted
30/01/2020
Date registered
13/02/2020
Date last updated
3/03/2020
Date data sharing statement initially provided
13/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD)
Scientific title
LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD): a randomised trial testing a community fibrosis assessment service for patients with suspected non-alcoholic fatty liver disease
Secondary ID [1] 299867 0
None
Universal Trial Number (UTN)
U1111-1247-1295
Trial acronym
LOCATE-NAFLD
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Non-Alcoholic Fatty Liver Disease 315277 0
Condition category
Condition code
Oral and Gastrointestinal 313574 313574 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Public Health 314439 314439 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The starting point for patients is when they visit a GP. If the GP has sufficient concerns about the patient’s liver health, they will write a referral letter requesting a specialist hepatology clinic. The GP may also request blood tests, or have already performed those tests. Referral letters will be screened by a hepatologist at the Sunshine Coast and Princess Alexandra Hospitals to identify patients eligible for the study. The details of potential patients will be
recorded for potential recruitment into the study.
After participants consent to participation, they will complete 3 short questionnaires - a short (5 question) demographics questionnaire, a quality of life questionnaire, and a questionnaire detailing their alcohol consumption. Based on the results of this third questionnaire, if their alcohol consumption is low enough for their liver damage to be considered not related to alcohol consumption (as per the exclusion criteria), they will be enrolled into the study, where they will be randomised to the new model of care (LOCATE) or usual care.
Study participants randomised to the new model of care will be invited to attend a local clinic to have their suspected NAFLD assessed using mobile transient elastography (TE), using a Fibroscan machine. Participants will be asked to lie on their back with their right arm raised
above their head. A gel will be applied to their skin on the right-hand side. A small hand held sensor is then pressed on the surface of the skin. The gel is wiped off at the end of the procedure.
The invitation and assessment will be made by a specialist study nurse trained in the use of the machine. A nurse will call the participants who need to be scheduled for a scan to organise a appointment time, and a follow-up text will be sent as an appointment reminder 48 hours before the scan is due to take place. Those who do not attend will be given the option to reschedule once, and we will record the reason for 'did not attends' if practical (i.e. they can be contacted and provide a reason). The intervention screening appointment will last approximately 30 minutes, with the actual screening process taking between 2-20 minutes to perform (participants will be told in advance that it can take 20 minutes to perform the scan). This will only need to occur once for the intervention. After the assessment the study nurse will write a report on the results and send it to the hepatologist for triage. The triage to low or high risk will depend on the assessment of liver scarring. Participants with low Fibroscan scores (TE under 8.0 kPa) will be classified as ‘Low Risk’. A letter will be sent to participants and their GPs about their test results and proposed management. Patients will be asked to make an appointment with their GP for review of the scan results and for GP advice on NAFLD management. They will then attend their planned hospital hepatology appointment.
Participants with clinically significant fibrosis (TE over 8.0 kPa) will be classified as ‘High Risk’ and will be sent a letter summarising their test results and asking them to call the hepatology clinic to arrange a clinic appointment. They may also be enrolled in HCC and variceal surveillance programs, as indicated. GPs will be sent a letter informing them of the results and proposed management by the hepatologist.
For those participants randomised to usual care, their referral letters will be dealt with in the usual way, and the patients wait to see a hepatologist as originally planned.
The Fibroscan service will enable participants to undergo reliable assessment of the degree of liver fibrosis (scarring) and to identify those with advanced fibrosis and cirrhosis who need both secondary care input and surveillance for liver cancer. The mobile clinics will occur on a rotational basis in the two regions using the GP clinics and primary care centres. This will make it easier for participants to keep their appointments, particularly those in rural areas.
Intervention code [1] 316269 0
Early detection / Screening
Comparator / control treatment
For those participants randomised to usual care, their referral letters will be dealt with in the usual way, and the patients wait to see a hepatologist at a hospital outpatient clinic, which can have waiting lists of 3 months or longer.
Control group
Active

Outcomes
Primary outcome [1] 322185 0
Time from baseline to diagnosis of high-risk NAFLD (significant fibrosis result - TE over 8.2 kPa). Fibrosis measurement is provided by the fibroscan results.
Timepoint [1] 322185 0
On completion of scan
Primary outcome [2] 322186 0
Evaluate the cost-effectiveness of the new model of care. This will be measured using hospital data, participant Medicare/Pharmaceutical Benefits Scheme cost and healthcare usage data, and QALYs based on quality of life results from pre- and post- participant screening.
Timepoint [2] 322186 0
Twelve months post baseline
Secondary outcome [1] 377610 0
Referral to a specialist (other than a hepatologist). This outcome can be assessed through participant's Medicare records from the 12 month follow up period.
Timepoint [1] 377610 0
12 months post baseline
Secondary outcome [2] 377611 0
Validation of results in intervention arm. This will be assessed by the comparison of the two sets of results by the leading hepatologist, and if necessary additional opinion and discussion may occur between this hepatologist and the other clinical investigator hepatologist on the study (without sharing identifiable details or data)
Timepoint [2] 377611 0
Twelve months post baseline
Secondary outcome [3] 377612 0
Time to first successful fibrosis assessment with Fibroscan. This is defined as the time between the date of referral by the GP to the first time a successful (i.e. scan is complete and results are obtained) scan is recorded. This will be assessed by the results of the fibroscan which will be recorded in the participants' medical records and will have the date and time of the scan reported.
Timepoint [3] 377612 0
Twelve months post baseline
Secondary outcome [4] 377613 0
Admissions to hospital. This data will be obtained from participant's MBS data, as well as their medical records as reviewed by the study nurse.
Timepoint [4] 377613 0
Twelve months post baseline
Secondary outcome [5] 377614 0
Presentations to an emergency department. This data will be obtained from participant's MBS data, as well as their medical records as reviewed by the study nurse.
Timepoint [5] 377614 0
Twelve months post baseline
Secondary outcome [6] 377615 0
Health-related quality of life. This will be assessed through participants completing the pre- and post-study EQ-5D-3L Quality of Life questionnaire by EuroQoL and comparing the results.
Timepoint [6] 377615 0
Baseline
Twelve months from baseline
Secondary outcome [7] 377616 0
Hepatocellular carcinoma (HCC) detected outside specific surveillance. This will be assessed through medical record review by the study nurse at the end of the follow up period.
Timepoint [7] 377616 0
12 months from baseline
Secondary outcome [8] 377617 0
Variceal bleeding occurring without variceal surveillance. This will be assessed through medical record review by the study nurse at the end of the follow up period.
Timepoint [8] 377617 0
Twelve months from baseline
Secondary outcome [9] 377618 0
Death
Timepoint [9] 377618 0
Twelve months from baseline

Eligibility
Key inclusion criteria
Patients will be included if they:
• Have had NAFLD diagnosed or suspected by their GP (from a GP referral letter).
• Are aged between 18 and 75 years old.
• Understand the consent procedures and give their full consent (See Section 13.1.2).
• Consent to access of their data from Queensland Health and MBS and PBS.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they:
• Are pregnant.
• Have advanced cardiac disease or another terminal illness.
• Have high current alcohol consumption, defined as two or more standard drinks per day.
• Have Hepatitis B or C (extracted from the GP referral letter).
• Require priority review at the Hepatology Clinic
• Have been evaluated in a specialist hepatology clinic in the previous 12 months.
• Have plans to leave the area within the next 12 months.

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)
Randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We aim to have a minimum total sample size of 156 participants for our primary outcome, but will aim for a sample size of 234. This number of participants will give us a 95% power to detect a 50% reduction in the primary outcome of time to diagnosis of high risk disease. Our minimal sample size of 156 participants gives us an 83% power. We used a two-sided 5% significance level. We assumed an average time of 180 days in the usual care group and halving of this time in the intervention group. We assumed that 5% of participants would be censored due to death or loss to follow-up. Participants still undiagnosed at 365 days were also censored, as this the end of follow-up. The sample size was estimated by simulating survival data using the “sim.survdata” function from the “coxed” package in R (ref) using 1,000 simulations. We assumed a log-normal hazard function with a standard deviation of 10 days. The statistical code to run the sample size is available here: https://github.com/agbarnett/LOCATE. We assume that half of all patients approached will agree to participate, hence we will need to approach 468.
We will present results as means and 95% confidence intervals. We will include p-values in our reports, but will aim not to present them in any external reports or papers given the widespread misunderstanding of their meaning.
An initial analysis will be created using a scrambled intervention group by randomly allocating each participant to the usual care or intervention period. A complete statistical report will be created using this scrambled data and sent to all investigators for discussion. This allows investigators to query the methods and approaches used prior to the final report. It can also uncover errors in the code or data. Changes can be made prior to seeing the main results, which helps avoid the bias of only making changes where results are perceived as unfavourable. We will use residual checks for all our models and will look for non-normality and outliers. We will consider using a log-transformation (base e) if the residuals show a strong skew.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 15403 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [2] 15404 0
Logan Hospital - Meadowbrook
Recruitment postcode(s) [1] 28720 0
4575 - Birtinya
Recruitment postcode(s) [2] 28721 0
4131 - Meadowbrook

Funding & Sponsors
Funding source category [1] 304329 0
Government body
Name [1] 304329 0
National Health and Medical Reserach Council
Address [1] 304329 0
16 Marcus Clarke St,
Canberra ACT 2601
Country [1] 304329 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
60 Musk Avenue
Kelvin Grove
QLD
4059
Country
Australia
Secondary sponsor category [1] 304574 0
University
Name [1] 304574 0
University of Queensland
Address [1] 304574 0
The University of Queensland
Herston
Brisbane
QLD
4072
Country [1] 304574 0
Australia
Secondary sponsor category [2] 305146 0
University
Name [2] 305146 0
University of the Sunshine Coast
Address [2] 305146 0
90 Sippy Downs Drive,
Sippy Downs
Queensland
4556
Country [2] 305146 0
Australia
Secondary sponsor category [3] 305147 0
Other Collaborative groups
Name [3] 305147 0
Queensland Institute of Medical Research (QIMR Berghofer Medical Reserach Institute)
Address [3] 305147 0
300 Herston Rd,
Herston
Brisbane City, QLD
4006
Country [3] 305147 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304780 0
Royal Brisbane Women's Hospital (Metro North Hospital and Health Service) Human Research Ethics Committee
Ethics committee address [1] 304780 0
Human Research Ethics Office
Executive Suites, Lower Ground Floor
Dr James Mayne Building
Royal Brisbane and Women’s Hospital
Butterfield Street, Herston,
Qld 4029
Ethics committee country [1] 304780 0
Australia
Date submitted for ethics approval [1] 304780 0
28/01/2020
Approval date [1] 304780 0
27/02/2020
Ethics approval number [1] 304780 0
HREC/2020/QRBW/6085

Summary
Brief summary
LOCATE-NAFLD is a randomised trial, comparing two alternative models of care for NAFLD (usual care versus LOCATE-NAFLD care). Participants randomised to the intervention will be screened in the community with a non-invasive device called a Fibroscan, a scan they may otherwise have waited months to receive. The scan results can then determine if their disease, with high risk patients sent to a specialist, and low-risk patients returned to the care of their GP, reducing unnecessary hospital appointments.

Through this faster assessment and stratification of patients in the community, the study aims to greatly reduce referrals for hospital-based appointments, and improve surveillance of high-risk disease, resulting in enhanced management of complications that result in avoidable, high cost hospital admissions.
Trial website
http://www.aushsi.org.au/research/nhmrc-funded-research/locate-nafld-study-2019-2022/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98174 0
Prof Adrian Barnett
Address 98174 0
Queensland University of Technology
60 Musk Avenue
Kelvin Grove, Brisbane
QLD, 4059
Country 98174 0
Australia
Phone 98174 0
+61 7 3138 6010
Fax 98174 0
Email 98174 0
a.barnett@qut.edu.au
Contact person for public queries
Name 98175 0
Prof Adrian Barnett
Address 98175 0
Queensland University of Technology
60 Musk Avenue
Kelvin Grove, Brisbane
QLD, 4059
Country 98175 0
Australia
Phone 98175 0
+61 7 3138 6010
Fax 98175 0
Email 98175 0
a.barnett@qut.edu.au
Contact person for scientific queries
Name 98176 0
Prof Adrian Barnett
Address 98176 0
Queensland University of Technology
60 Musk Avenue
Kelvin Grove, Brisbane
QLD, 4059
Country 98176 0
Australia
Phone 98176 0
+61 7 3138 6010
Fax 98176 0
Email 98176 0
a.barnett@qut.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All final non-identifiable data sets will be available once the main papers have been published. All collected data will be shared except MBS and PBS data.
When will data be available (start and end dates)?
Ater publication of main papers (approx. June 2022). No end date.
Available to whom?
Available publicly
Available for what types of analyses?
Any purpose
How or where can data be obtained?
The complete statistical code will be published and fully accessible on github (https://github.com/agbarnett/LOCATE). All final non-identifiable data sets will be available from the study statistician (CI Barnett).
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 6674 0
Study protocol
Citation [1] 6674 0
Link [1] 6674 0
Email [1] 6674 0
a.barnett@qut.edu.au
Other [1] 6674 0
Protocol will be available by attachment once approved by ethics
Attachment [1] 6674 0
Summary results
No Results