Testing for liver scarring at the diabetes annual review
| ISRCTN | ISRCTN14585543 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14585543 |
| IRAS number | 299934 |
| Secondary identifying numbers | CPMS 51136, IRAS 299934 |
- Submission date
- 22/04/2022
- Registration date
- 27/04/2022
- Last edited
- 25/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Changes in the liver are common among people with diabetes and are mostly due to fat buildup. This condition is called non-alcoholic fatty liver disease (NAFLD) and is found in up to two-thirds of people living with type 2 diabetes (T2D). In some cases patients with NAFLD are not at particularly increased risk of developing serious liver disease, but in some patients NAFLD can take a more progressive form that involves inflammation and scarring in the liver (non-alcoholic steatohepatitis or NASH) that can progress to cirrhosis, liver failure and liver cancer. Sadly people with diabetes are at increased risk of developing NASH and scarring in the liver. Researchers want to identify people who will develop serious liver disease in the earlier stages, when something can be done to stop progression.
For most people, there are no symptoms of fatty liver, scarring or even cirrhosis until the latest stages of disease when treatment is less effective. Routine blood tests do not diagnose scarring or cirrhosis, but it is possible to calculate scores from these tests, such as the Fib-4 used in this study to accurately rule out significant disease. If Fib-4 is negative, we can be fairly confident that patients do not have significant fibrosis. If Fib-4 is positive, then patients should have further specialist investigations.
This study will focus on people in GP practices with T2D because they have an annual review that includes blood tests, to which a Fib-4 test will be added. Patients who have positive test results will be referred for a liver fibrosis scan either at their local hospital or GP practice. If Fib-4 testing in the annual review identifies more patients with fibrosis and is cost-effective, this test could be introduced across the NHS to target treatment and reduce the number of people who develop liver cancer or liver failure.
Who can participate?
Patients aged 18 years and over with type 2 diabetes who are registered at the GP practices participating in the study
What does the study involve?
Participants will not experience anything different at their annual review and blood samples will be taken in the normal way – only one blood draw is needed as normal for the annual review. Depending on the blood tests the practice does as standard, participants may not need to give any extra blood. If the Fib-4 blood test cannot exclude significant liver scarring, participants will be told and invited to have a special scan of the liver called a Fibroscan. This is a quick test (10 minutes) that involves applying jelly to the abdomen and running a probe over the liver. It is not painful and there are no needles involved. This might take place at a local hospital or at a location in or near the GP practice.
A small number of people will be asked to take part in an optional interview and/or focus group to explore people’s thoughts about liver screening alongside the diabetes annual review and the experience of being involved in this study. This interview and/or focus group would take place either in person at the GP practice, other NHS sites, or alternatively online/by telephone. This should take less than 90 minutes. The researchers wish to audio or video record this interview/focus group to record what is said. These recordings will then be destroyed after transcription to a written record. Transcription of interviews will be undertaken by the study team in an anonymised format. Afterwards the researchers may wish to contact participants to ask follow up questions based on comments from other patient interviews before completion of the study. Direct quotes from interviews may be published alongside the results of this study without any details that could identify participants.
What are the possible benefits and risks of participating?
If the results of the examinations performed in this study identify any abnormalities with the liver then participants will be referred to their local hospital liver clinic for routine clinical care.
Where is the study run from?
Barts Health NHS Trust (UK)
When is the study starting and how long is it expected to run for?
January 2020 to September 2024
Who is funding the study?
Gilead Sciences (USA)
Who is the main contact?
bartshealth.rlhprelude1@nhs.net
+44 (0)20 7882 8610
Contact information
Scientific
Queen Mary, University of London
School of Medicine and Dentistry, Blizard Institute
Centre for Immunobiology
4 Newark St
London
E1 2AT
United Kingdom
 ORCID ID |
0000-0002-7029-9891 |
|---|---|
| Phone | +44 (0)20 7882 8610 |
| Hal.brindley@nhs.net |
Scientific
Queen Mary University of London
Blizard Institute
4 Newark Street
London
E1 2AT
United Kingdom
| ORCID ID |
0000-0002-3891-5914 |
|---|---|
| Phone | +44 (0)2078822308 |
| w.alazawi@qmul.ac.uk |
Study information
| Study design | Non-randomized; Both; Design type: Screening, Diagnosis, Process of Care, Management of Care, Cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | 41611_PIS_V1.4_11Mar22.pdf |
| Scientific title | Feasibility and acceptability of a primary care liver fibrosis testing pathway centred on the diabetes annual review |
| Study acronym | PRELUDE-1 |
| Study objectives | Liver fibrosis screening using FIB-4 and Fibroscan will prove feasible in primary care as a component of the diabetes annual review. |
| Ethics approval(s) | Approved 15/02/2022, East of England - Cambridge East Research Ethics Committee (The Old Chapel Royal Standard Place Nottingham NG1 6FS, UK; +44 (0)207 104 8102, +44 (0)2071048265; CambridgeEast.REC@hra.nhs.uk), ref: 21/EE/0269 |
| Health condition(s) or problem(s) studied | Liver fibrosis |
| Intervention | This is a prospective cohort study of automated fibrosis testing in patients with type 2 diabetes linked to a trial of hospital-based versus community-based second-tier testing. The overall strategy is to determine whether focussing on at-risk type 2 diabetes patients, without a priori recognition or suspicion of nonalcoholic fatty liver disease (NAFLD), is a feasible and acceptable approach to fibrosis testing in the community. This study takes advantage of the mature nationwide programme of annual diabetes review and the performance-based remuneration system in UK primary care. Blood requests will be automatically generated at the review and the Fib-4 automatically calculated from these results and an action plan recommended based on the threshold of 1.3. Practices allocated to the hospital arm will send the referral to hospital as per existing local referral pathways. Practices in the community arm send electronic referrals to a dedicated NHS address and a member of the NHS care team will arrange an appointment for the patient at the community centre. Results from Fibroscans will be returned to the GP practice for coding in primary care records and clinical action. Study procedures: 1. Practice-wide consent to take part in PRELUDE-1 2. Adoption and agreement to include Fib-4 test at diabetes annual review alongside standard biochemistry tests 3. Patients with indeterminate/high risk (Fib-4 >1.3) scores proceed to either community or hospital Fibroscan (pre-determined for each practice in this feasibility study) 4. Patients with Fibroscan >7.9 kPa referred to local hepatology services 5. Data extraction from EMIS 2021-22 6. Data extraction from EMIS 2022-23 The intervention builds on existing infrastructure and data extraction/audit tools that are already built into the routine care software packages that are in use in >90% of UK GP practices. This means that anonymised data can be extracted using Read codes (version CTV3) for “Diabetes Annual Review” or “Diabetes Type 2 Review” as the primary handle. The researchers will extract demographic and clinicopathological data to include ethnicity, social deprivation, partial postcode, medical history including alcohol consumption, medication use, blood and imaging results including liver aetiology screen. They will work with data using a remote secure server under the guidance of the the QMUL Research data access and management policy. Cost-effectiveness The researchers will undertake an exploratory cost-utility analysis of protocolled versus historic opportunistic testing for fibrosis in order to construct a Markov model of lifetime costs from a health and social care perspective and quality-adjusted life expectancy, considering current and potential novel drug therapies. The structure will be informed by a conceptual modelling phase, but is likely to include health states representing cirrhosis, decompensation and transplantation. The model will be parameterised following a structured literature search. Parameters on prevalence of fibrosis will be informed by the trial. The model will be probabilistic and results will be reported in the form of cost-effectiveness acceptability curves. Identifying attitudes The qualitative arm will comprise a semi-structured interview/focus group with primary care staff (GPs and practice nurses), and a semi-structured interview with patients taking part in the wider study. Purposive sampling across relevant key characteristics (e.g., job role, length of time in role, ethnicity, age, and gender) will be used to capture varying levels of staff clinical experience and knowledge, as well as diversity in sociodemographic factors. No sample size has been set as the target is saturation of themes. However, based on previous studies and to facilitate adequate purposive sampling, a minimum of 30 participants (15 staff and 15 patients) is a reasonable approximation. Interviews/focus groups will be scheduled to take place at the most convenient time for participants. Relevant routine departmental or practice meetings will be utilised where possible for staff focus groups to reduce burden on resources. Flexibility will be provided in cases where group participation is not possible, offering individual semi-structured interviews where preferred. Participation will involve a single session interview or focus group of approximately 60 minutes in duration. The topic guides are devised from the study aims and from background literature on liver screening in primary care. PPI groups have also reviewed the study materials and methodologies and feedback has been incorporated accordingly. Topic guides will be used flexibly to facilitate the process of qualitative data collection, with scope for discussion of other topics that participants find salient. The staff topic guide focuses on attitudes towards non-alcoholic steatohepatitis (NASH) and liver fibrosis in diabetes, typical experiences of testing for fibrosis in primary care, and assessment guidelines. Specifically, the interviews will explore experiences of perceived advantages and disadvantages of the assessment strategy and the barriers and facilitators to implementing protocolled screening for liver fibrosis beyond the trial context. For patients, the topic guide focuses on overall experiences of taking part in the study, comprehension and impact of assessment, and knowledge of risk factors and health behaviours for NASH and fibrosis pre and post-test. This work will inform the implementation strategy for the subsequent trial phase and help us understand why previous guidance has not resonated with the community. |
| Intervention type | Other |
| Primary outcome measure | Proportion of individuals with type 2 diabetes with indeterminate or high-risk Fib-4 scores at the diabetes annual review |
| Secondary outcome measures | 1. Proportion of patients referred for Fibroscan who attend in community vs hospital, measured at the end of the study 2. Exploratory cost-utility analysis of protocolled versus historic opportunistic testing for fibrosis, measured at the end of the study 3. Qualitative analysis of attitudes among primary care physicians towards NASH and liver fibrosis in diabetes, testing for fibrosis in primary care, and assessment guidelines, using structured interviews/focus groups at the end of the study 4. Proportion of individuals with indeterminate or high-risk Fib-4 who have raised fibroscan scores measured at the end of the study |
| Overall study start date | 10/01/2020 |
| Completion date | 01/09/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 5300; UK Sample Size: 5300 |
| Key inclusion criteria | 1. General practice with >4000 registered patients 2. Practice lead, or representative, confirms agreement to participate in the study after reading the practice information sheet 3. Practice lead, or representative, confirms practice support introduction of Fib-4 testing for all patients with type 2 diabetes attending for annual review 4. Track record of >85% of patients with type 2 diabetes attending for diabetes review 5. Practice uses EMIS computer system 6. Referral route for fibroscan based on primary care non-invasive score agreed Patient inclusion criteria: 1. Type 2 diabetes 2. Serum biochemistry sample taken alongside diabetes annual review |
| Key exclusion criteria | 1. Inclusion criteria not met 2. Practice participating in other screening or case-finding study related to liver fibrosis |
| Date of first enrolment | 02/05/2022 |
| Date of final enrolment | 01/11/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
80 Newark Street
London
E1 2ES
United Kingdom
School of Medicine and Dentistry
Blizard Institute
4 Newark St
London
E1 2AT
United Kingdom
Canynge Hall
Whatley Road
Bristol
BS8 2PS
United Kingdom
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Bristol
BS2 8HW
United Kingdom
London
E1 1FR
United Kingdom
Sponsor information
University/education
Research Services Dept W.
68-89 Mile End Road
London
E1 4UJ
England
United Kingdom
| Phone | +44 (0)2078827275 |
|---|---|
| research.governance@qmul.ac.uk | |
| Website | http://www.qmul.ac.uk/ |
"ROR" |
https://ror.org/026zzn846 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Gilead, Gilead Sciences, Inc.
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/05/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication of study protocol in coming months and then subsequent publication of trial data around 1 year after completion of the study in peer-reviewed journals |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.4 | 11/03/2022 | 22/04/2022 | No | Yes |
| Protocol article | 19/05/2023 | 22/05/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | Baseline Data - conference Abstract | 19/05/2023 | 25/11/2024 | Yes | No |
| Other publications | aseline Data - conference Abstract | 19/05/2023 | 25/11/2024 | Yes | No |
| Other publications | qualitative process evaluation | 13/10/2024 | 25/11/2024 | Yes | No |
| Other publications | qualitative process evaluation | 13/10/2024 | 25/11/2024 | Yes | No |
Additional files
Editorial Notes
25/11/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 02/05/2023 to 01/11/2023.
2. The overall end date was changed from 02/11/2023 to 01/09/2024.
3. The intention to publish date was changed from 02/11/2024 to 01/05/2025.
4. The plain English summary was updated to reflect these changes.
5. Publication references added.
22/05/2023: Publication reference added.
22/04/2022: Trial's existence confirmed by the NIHR.
