IBD-RESPONSE – predicting treatment response in Crohn’s disease and ulcerative colitis
| ISRCTN | ISRCTN96296121 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN96296121 |
| IRAS number | 295742 |
| Secondary identifying numbers | CPMS 49964, MR/T032162/1, IRAS 295742 |
- Submission date
- 17/11/2021
- Registration date
- 29/12/2021
- Last edited
- 20/01/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English Summary
Background and study aims
Crohn's disease and ulcerative colitis (UC) are types of a bowel condition known as inflammatory bowel disease (IBD) and the symptoms (diarrhoea, pain, fatigue) have a major impact on daily life. IBD affects around 1 in 125 people in the UK and this is expected to rise to 1 in 100 by 2028. "Biologics" are powerful medications that are given to reduce inflammation in IBD. These treatments can be effective but up to 40% of patients don't respond, and in those that do, many don't respond well enough to stay on the drug after one year of treatment. Unfortunately, we have no way to predict which patients are most likely to benefit from treatment (known as responders), and we do not fully understand how medications work in responders. As these drugs may have serious side effects and are expensive to the NHS, this lack of understanding is a major obstacle in deciding which treatment is best to give to an individual patient, and when to give it to them in order to have the greatest benefit and the least risk. Recent data from small studies in people with IBD and larger studies of people with cancer, show that certain bacteria in stool may predict who will respond or fail to respond to treatments.
Who can participate?
We will recruit 1,325 patients starting biological therapy in IBD as part of routine NHS care from 40 centres across the UK.
What does the study involve?
We will collect stool, blood and where possible intestinal biopsies during routine endoscopy (camera into the gut), to study the gut bacteria before, and during, these treatments.
What are the possible benefits and risks of participating?
Benefits: In the short term this study will not help the participant directly as the results will not change any standard of care treatment received. However, the information we get from this study will help to improve our understanding of the links between gut microbes, genes, diet and Inflammatory Bowel Disease. Our goal is to better understand the complicated relationship between these different factors and Inflammatory Bowel Disease. Our aim is to use this information to create a tool that can predict response to treatment in Inflammatory Bowel Disease. In the future, we hope it will benefit lots of Inflammatory Bowel Disease patients, by helping to select the best drug at the right time for individual patients.
Risks: By joining the study, participants will donate blood samples and biopsies (only if you have an endoscopy during the study period), which are routinely collected as part of the participants clinical standard of care. Blood sampling can cause momentary discomfort and may cause a small bruise. The biopsy procedure carries a small risk of bleeding and there is a very minimal risk, that the procedure could create a hole in the bowel (perforation). The specific risks of undergoing a colonoscopy or flexible sigmoidoscopy are discussed with the participant in line with the NHS consent process for each endoscopic procedure as part of standard NHS practice.
Where is the study run from?
Newcastle Clinical Trials Unit (UK)
When is the study starting and how long is it expected to run for?
January 2021 to December 2026
Who is funding the study?
1. Medical Research Council (UK)
2. Leona M. and Harry B. Helmsley Charitable Trust (USA)
Who is the main contact?
IBD.Response@newcastle.ac.uk
Contact information
Scientific
Newcastle Clinical Trials Unit
1–4 Claremont Terrace
Newcastle University
Newcastle upon Tyne
NE2 4AE
United Kingdom
| IBD.Response@newcastle.ac.uk |
Scientific
Newcastle Clinical Trials Unit
1–4 Claremont Terrace
Newcastle University
Newcastle upon Tyne
NE2 4AE
United Kingdom
| IBD.Response@newcastle.ac.uk |
Scientific
Newcastle Clinical Trials Unit
1–4 Claremont Terrace
Newcastle University
Newcastle upon Tyne
NE2 4AE
United Kingdom
| christopher.lamb@newcastle.ac.uk |
Scientific
Newcastle Clinical Trials Unit
1–4 Claremont Terrace
Newcastle University
Newcastle upon Tyne
NE2 4AE
United Kingdom
| IBD.Response@newcastle.ac.uk |
Study information
| Study design | Observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | ISRCTN96296121_PIS_V5.0_09Jun23.pdf |
| Scientific title | Defining microbial predictors of responsiveness to biologic therapies in Crohn’s disease and ulcerative colitis |
| Study acronym | IBD-RESPONSE |
| Study hypothesis | To identify and validate a predictive model for response or failure to respond to biologic and janus kinase inhibitor (JAKi) therapies in Crohn’s disease (CD) and ulcerative colitis (UC), the major forms of inflammatory bowel disease (IBD), using microbiome (including microbial species and functional data), metabolome and integrated clinical and human genome data. |
| Ethics approval(s) | Approved 16/08/2021, Wales Research Ethics Committee 5 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; +44 1874 615950; Wales.REC5@Wales.nhs.uk), ref: 21/WA/0228 |
| Condition | Crohn’s disease and ulcerative colitis |
| Intervention | Current interventions as of 19/12/2024: This is a multi-centre, observational cohort study with 40 centres across the United Kingdom. We will aim to recruit 1325 participants over 27 months. Patients will be identified by the gastroenterology teams and be screened against the study eligibility criteria using the patients' medical records. Eligible patients will have the study explained to them by a member of the study team and be given the Patient information sheet for further information. Patients (up to 300 patients) who are diagnosed with Crohn' disease may be asked to be part of the sub-study called CD-metaRESPONSE, which means they complete some extra questionnaires and collect additional samples. To be eligible for the study, the participant will need to be starting a biologic therapy (an injectable medication used to control inflammation in inflammatory bowel disease e.g. infliximab, adalimumab, vedolizumab or ustekinumb) or a JAK inhibitor medication (tofacitinib) as treatment for Crohn’s disease or ulcerative colitis. The majority of the study will be completed remotely, at participants' home. Each participant will be provided with access to the online database, REDCap, which will be used to provide informed consent, complete questionnaires and track samples. Participants will be enrolled for approximately 54 weeks, with assessments performed at baseline (prior to starting treatment), week 14 (14 weeks after starting treatment) and at week 54 (54 weeks after starting treatment). These visits should align with patients dosing regimen. The IBD-RESPONSE research team at site will be available to support and help with any questions or concerns about the study. Assessment 1 (Baseline) - (up to 6 weeks prior to starting treatment) 1. Complete questionnaires assessing Health related quality of life; PRO-2 (CD) or PRO-2 (UC), PROMIS-Fatigue, IBD-Control, International Physical Activity Questionnaire (IPAQ) and EQ-5D-5L. Participants dietary habits will also be assessed using Scottish Collaborative Group Food Frequency Questionnaire and for participants in the CDmetaRESPONSE cohort - Kings College London 4-day food diary. 2. Collect Stool Samples at home and send to research team at Newcastle University. 3. If attending a routine clinical appointment, approximately 20ml of blood samples will be collected for analysis. These samples will be sent to by the research team to Wellcome Sanger Institute for analysis. Assessment 2 - (14 weeks after starting treatment (ideally +/- 2 weeks but data can be collected between weeks 10-20)) 1. Complete questionnaires assessing Health related quality of life; PRO-2 (CD) or PRO-2 (UC), PROMIS-Fatigue, IBD-Control, International Physical Activity Questionnaire (IPAQ) and EQ-5D-5L. Participants dietary habits will also be assessed using Scottish Collaborative Group Food Frequency Questionnaire and for participants in the CDmetaRESPONSE cohort - Kings College London 4-day food diary. 2. Collect Stool Samples at home and send to research team at Newcastle University 3. If attending a routine clinical appointment, approximately 20ml of blood samples will be collected for analysis. These samples will be sent to by the research team to Wellcome Sanger Institute for analysis. Assessment 3 - (54 weeks after starting treatment (+/- 6 weeks)) 1. Complete questionnaires assessing Health related quality of life; PRO-2 (CD) or PRO-2 (UC), PROMIS-Fatigue, IBD-Control, International Physical Activity Questionnaire (IPAQ) and EQ-5D-5L. Participants dietary habits will also be assessed using Scottish Collaborative Group Food Frequency Questionnaire and for participants in the CDmetaRESPONSE cohort - Kings College London 4-day food diary. 2. Collect Stool Samples at home and send to research team at Newcastle University 3. If attending a routine clinical appointment, approximately 20ml of blood samples will be collected for analysis. These samples will be sent to by the research team to Wellcome Sanger Institute for analysis. If a participant change their treatment prior to first follow-up (Assessment 2), they will be asked to complete questionnaires/provide samples required at Assessment 2 at the time of stopping treatment. If you start a new treatment after this, the planned follow-up timeline will restart at Assessment 2, 14 weeks after starting the new treatment. If the participant changes their treatment after Assessment 2 but before completing Assessment 3, they will be asked to complete questionnaires/provide samples required at Assessment 3 at the time of stopping treatment. If you start a new treatment after this, the planned follow-up timeline will restart at Assessment 2, 14 weeks after starting the new treatment. If a participant is scheduled for an endoscopy (colonoscopy or flexi sigmoidoscopy) during the study, they will be asked to consent to research team taking up to 12 biopsies for the study. The biopsies will be sent by the research team to Wellcome Sanger Institute (up to 6 biopsies) and to Newcastle University (up to 6 biopsies) for analysis. _____ Previous interventions: This is a multi-centre, observational cohort study with 40 centres across the United Kingdom. We will aim to recruit 1325 participants over 27 months. Patients will be identified by the gastroenterology teams and be screened against the study eligibility criteria using the patients' medical records. Eligible patients will have the study explained to them by a member of the study team and be given the Patient information sheet for further information. Patients (up to 200 patients) who are diagnosed with Crohn' disease may be asked to be part of the sub-study called CDmetaRESPONSE, which means they complete some extra questionnaires and collect additional samples. To be eligible for the study, the participant will need to be starting a biologic therapy (an injectable medication used to control inflammation in inflammatory bowel disease e.g. infliximab, adalimumab, vedolizumab or ustekinumb) or a JAK inhibitor medication (tofacitinib) as treatment for Crohn’s disease or ulcerative colitis. The majority of the study will be completed remotely, at participants' home. Each participant will be provided with access to the online database, REDCap, which will be used to provide informed consent, complete questionnaires and track samples. Participants will be enrolled for approximately 54 weeks, with assessments performed at baseline (prior to starting treatment), week 14 (14 weeks after starting treatment) and at week 54 (54 weeks after starting treatment). These visits should align with patients dosing regimen. The IBD-RESPONSE research team at site will be available to support and help with any questions or concerns about the study. Assessment 1 (Baseline) - (up to 6 weeks prior to starting treatment) 1. Complete questionnaires assessing Health related quality of life; PRO-2 (CD) or PRO-2 (UC), PROMIS-Fatigue, IBD-Control, International Physical Activity Questionnaire (IPAQ) and EQ-5D-5L. Participants dietary habits will also be assessed using Scottish Collaborative Group Food Frequency Questionnaire and for participants in the CDmetaRESPONSE cohort - Kings College London 4-day food diary. 2. Collect Stool Samples at home and send to research team at Newcastle University. 3. If attending a routine clinical appointment, approximately 20ml of blood samples will be collected for analysis. These samples will be sent to by the research team to Wellcome Sanger Institute for analysis. Assessment 2 - (14 weeks after starting treatment (ideally +/- 2 weeks but data can be collected between weeks 10-20)) 1. Complete questionnaires assessing Health related quality of life; PRO-2 (CD) or PRO-2 (UC), PROMIS-Fatigue, IBD-Control, International Physical Activity Questionnaire (IPAQ) and EQ-5D-5L. Participants dietary habits will also be assessed using Scottish Collaborative Group Food Frequency Questionnaire and for participants in the CDmetaRESPONSE cohort - Kings College London 4-day food diary. 2. Collect Stool Samples at home and send to research team at Newcastle University 3. If attending a routine clinical appointment, approximately 20ml of blood samples will be collected for analysis. These samples will be sent to by the research team to Wellcome Sanger Institute for analysis. Assessment 3 - (54 weeks after starting treatment (+/- 6 weeks)) 1. Complete questionnaires assessing Health related quality of life; PRO-2 (CD) or PRO-2 (UC), PROMIS-Fatigue, IBD-Control, International Physical Activity Questionnaire (IPAQ) and EQ-5D-5L. Participants dietary habits will also be assessed using Scottish Collaborative Group Food Frequency Questionnaire and for participants in the CDmetaRESPONSE cohort - Kings College London 4-day food diary. 2. Collect Stool Samples at home and send to research team at Newcastle University 3. If attending a routine clinical appointment, approximately 20ml of blood samples will be collected for analysis. These samples will be sent to by the research team to Wellcome Sanger Institute for analysis. If a participant change their treatment prior to first follow-up (Assessment 2), they will be asked to complete questionnaires/provide samples required at Assessment 2 at the time of stopping treatment. If you start a new treatment after this, the planned follow-up timeline will restart at Assessment 2, 14 weeks after starting the new treatment. If the participant changes their treatment after Assessment 2 but before completing Assessment 3, they will be asked to complete questionnaires/provide samples required at Assessment 3 at the time of stopping treatment. If you start a new treatment after this, the planned follow-up timeline will restart at Assessment 2, 14 weeks after starting the new treatment. If a participant is scheduled for an endoscopy (colonoscopy or flexi sigmoidoscopy) during the study, they will be asked to consent to research team taking up to 12 biopsies for the study. The biopsies will be sent by the research team to Wellcome Sanger Institute (up to 6 biopsies) and to Newcastle University (up to 6 biopsies) for analysis. |
| Intervention type | Other |
| Primary outcome measure | 1. Stool frequency and rectal bleeding measured by PRO-2 at 14 weeks 2. Absence of rectal bowel surgery up to 14 weeks (yes/no) measured using patient records 3. Use of oral corticosteroids at 14 weeks (yes/no) measured using patient records |
| Secondary outcome measures | 1. Stool frequency and rectal bleeding measured by PRO-2 at baseline, week 14, and week 54 2. Absence of rectal bowel surgery up to 54 weeks (yes/no) measured using patient records 3. Use of oral corticosteroids at 14 weeks and 54 weeks (yes/no) measured using patient records 4. Time to treatment escalation (if applicable) up to 54 weeks measured using patient records, defined as: 4.1 Biologic or JAKi switch due to lack of efficacy/those with loss of response (does not include biosimilar switch or switch from i.v. to s.c.). 4.2 Dose intensification of drug due to lack of efficacy (does not include intensification based on therapeutic drug monitoring without flare in responders). 4.3 Re-sectional intestinal surgery (does not include examination under anaesthesia procedures in patients with perianal Crohn’s disease). 4.4 Induction or dose escalation of corticosteroids. 5. Time to discontinuation of index drug (if applicable) up to 54 weeks measured using patient records 6. Adverse events up to 54 weeks measured using patient records 7. Development of anti-drug antibodies measured using blood test at week 14 and 54 8. C-reactive protein (CRP) measured using blood test at baseline, week 14, and week 54 9. Faecal calprotectin measured using stool sample at baseline, week 14, and week 54 10. Remission measured by endoscopy during follow up (Mayo endoscopic subscore ≤1 for ulcerative colitis or SES-CD ≤2 for Crohn’s disease) 11. Quality of life measured using EQ-5D-5L and IBD-Control questionnaires at baseline, week 14, and week 54 12. Physical activity measured using International Physical Activity Questionnaire (IPAQ) at baseline, week 14, and week 54 13. Dietary intake measured using the Scottish Collaborative Group Food Frequency Questionnaire (FFQ) and the Kings College London 4-day food diary for CD-metaRESPONSE sub cohort participants only, at baseline, week 14, and week 54 14. Fatigue measured using the PROMIS-Fatigue 8a Short Form at baseline, week 14, and week 54 |
| Overall study start date | 01/01/2021 |
| Overall study end date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1325; UK Sample Size: 1325 |
| Participant inclusion criteria | 1. Adults aged 16 years and over. 2. Established diagnosis of inflammatory bowel disease: Crohn’s disease, ulcerative colitis or IBD-U. 3. Already participating or willing to participate in IBD BioResource. 4. Willing and able to provide informed consent. 5. Willing to undertake the following study procedures: 5.1. Completion of questionnaires. 5.2. Collection of stool specimens at home. 5.3. Provision of the requested biosamples during visits to hospital. 6. Intention of clinical team to commence anti-TNFα (infliximab or adalimumab), anti-integrin (vedolizumab), anti-IL12/23 (ustekinumab) biologic or JAKi (tofacitinib) therapy, for active luminal IBD within 6 weeks. 7. Additional inclusion criteria for patients with Crohn’s disease 8. Patients with Crohn’s disease must have at least one of the following documented within 12 weeks prior to consent: 9. Faecal calprotectin >=250 µg/g. 10. CRP >=6 mg/L. 11. Any endoscopic evidence of active Crohn’s disease, defined as ulceration (with at least one ulcer >=5mm) judged locally from available clinical data (as an approximation equivalent to SES-CD of >=4 for ileal disease or >=6 for ileocolonic or colonic disease. This can be estimated retrospectively from clinical record and does not have to be prospectively calculated). 12. Active inflammatory disease on imaging (MRI/CT/ultrasound) judged locally from available clinical data. 13. Additional inclusion criteria for participants with ulcerative colitis 14. Patients with ulcerative colitis must have at least one of the following documented within 12 weeks prior to consent: 15. Faecal calprotectin >=250 µg/g 16. CRP >=6 mg/L 17. Any endoscopic evidence of at least moderately active ulcerative colitis (of any extent including proctitis), defined as features of Mayo endoscopy sub-score > = 2 (marked erythema, lack of vascular pattern, friability, erosions, spontaneous bleeding or ulceration). This assessment will be judged locally and retrospectively from available clinical data and does not have to be prospectively calculated. 18. NOTE: Patients do not have to be biologic-naïve. Any additional biologics or small molecule newly licensed for Crohn’s disease or ulcerative colitis during the IBD-RESPONSE planned study period will also be suitable to allow inclusion. |
| Participant exclusion criteria | 1. Receiving oral corticosteroids for any indication where the dose is unlikely to be weaned by week 14. 2. Planned bowel resection surgery within 14 weeks of commencing therapy. 3. Biologic or JAKi being commenced as rescue therapy for acute severe ulcerative colitis (ASUC). 4. Biologic or JAKi being commenced as part of CTIMP. 5. Ileal pouch anal anastomosis. 6. Presence of a stoma. 7. Perianal Crohn’s disease in absence of active luminal inflammation. 8. Faecal microbial transplantation (FMT) within the preceding 12 weeks or planned FMT within 14 weeks of commencing biologic or JAKi. 9. Antibiotics or short-term (<=4 weeks) course of probiotics within the preceding 2 weeks. 10. NOTE: Use of long-term (>4 weeks), stable doses of probiotics is not an exclusion from this study but should be noted in the CRF. Use of antibiotics or prior FMT outside of the exclusion time period are not exclusions. Antibiotic use in the preceding 1 year and ever having received FMT will be noted in the CRF. |
| Recruitment start date | 31/12/2021 |
| Recruitment end date | 31/08/2026 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Freeman Road
High Heaton
Newcastle
NE7 7DN
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
London
SE1 7EH
United Kingdom
Edinburgh
EH1 3EG
United Kingdom
London
E1 2ES
United Kingdom
Praed Street
London
W2 1NY
United Kingdom
Oxford
OX3 9DU
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Coreys Mill Lane
Stevenage
SG1 4AB
United Kingdom
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Kettering
NN16 8UZ
United Kingdom
Shrewsbury
SY3 8XQ
United Kingdom
London Road
Reading
RG1 5AN
United Kingdom
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Newton Road
Torquay
TQ2 7AA
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
London
NW1 2PG
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Bath
BA1 3NG
United Kingdom
Seaway Drive
Seaway Parade Industrial Estate
Baglan
Port Talbot
SA12 7BR
United Kingdom
Longfleet Road
Poole
BH15 2JB
United Kingdom
Taunton
TA1 5DA
United Kingdom
London
SE5 9RS
United States of America
Maes-Y-Coed Road
Cardiff
CF14 4HH
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Walsgrave
Coventry
CV2 2DX
United Kingdom
Darlington
DL3 6HX
United Kingdom
Victoria Road
Macclesfield
SK10 3BL
United Kingdom
Redhill
RH1 5RH
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Crank Road
Crank
St. Helens
WA11 7RS
United Kingdom
Rake Lane
North Shields
NE29 8NH
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Eccles
Salford
M6 8HD
United Kingdom
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Harton Lane
South Shields
NE34 0PL
United Kingdom
Uxbridge Road
Southall
UB1 3HW
United Kingdom
Watford Road
Harrow
HA1 3UJ
United Kingdom
Brighton
BN2 5BE
United Kingdom
Sponsor information
Hospital/treatment centre
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
England
United Kingdom
| Phone | +44 1912824452 |
|---|---|
| christopher.price6@nhs.net | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Helmsley Charitable Trust, The Leona M. and Harry B. Helmsley Charitable Trust, Leona M. & Harry B. Helmsley Charitable Trust, The Helmsley Charitable Trust
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Raw data files in the original format (e.g., fastq) and the accompanying phenotypic data will be uploaded to the NCBI database of Genotypes and Phenotypes (dbGaP) at https://www.ncbi.nlm.nih.gov/gap/. Appropriate fully anonymised study data will be also be linked from the data.ncl.ac.uk institutional research data repository, and archived by the HDRUK IBD Digital Innovation Hub “G.I. Know” funded by UKRI. Our policy is to make the study data available 6 months after the full, cleaned data set is available. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | version 5.0 | 09/06/2023 | 23/01/2024 | No | Yes |
| Protocol article | 17/04/2024 | 18/04/2024 | Yes | No |
Additional files
Editorial Notes
20/01/2025: The following changes were made to the study record:
1. The recruitment end date was changed from 31/01/2025 to 31/08/2026.
2. The overall study end date was changed from 31/10/2025 to 31/12/2026.
3. The intention to publish date was changed from 01/10/2025 to 31/12/2026.
19/12/2024: The following changes were made to the trial record:
1. The interventions were changed.
2. The location 'Northern Ireland' was removed.
03/07/2024: The recruitment end date was changed from 31/07/2024 to 31/01/2025.
07/05/2024: The study participating centres were updated to add University Hospital Coventry & Warwickshire, Darlington Memorial Hospital, Macclesfield District General Hospital, East Surrey Hospital, Wythenshawe Hospital, Norfolk and Norwich University Hospital, Fairfield Hospital, North Tyneside General Hospital, Royal Free Hospital, Salford Royal Hospital, Kings Mill Hospital, The James Cook University Hospital, South Tyneside Hospital, St Marks Hospital & Ealing Hospital, and Royal Sussex County Hospital; and to remove Northwick Park Hospital, North Manchester General Hospital, Gartnavel Royal Hospital, Queen Alexandra Hospital, Thompson House Hospital, NHS Tayside, Chelsea & Westminster Hospital, and Russells Hall Hospital.
18/04/2024: Publication reference added.
23/01/2024:The following changes were made to the study record:
1. Participant information sheet uploaded.
2. Contact details updated.
3. Study website added.
4. The recruitment end date was changed from 30/04/2024 to 31/07/2024.
5. The overall study end date was changed from 31/10/2024 to 31/10/2025.
02/03/2023: The recruitment end date was changed from 31/12/2023 to 30/04/2024.
09/01/2023: Contact details updated.
17/11/2021: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
