Comparing treatments for diabetic foot ulcers
| ISRCTN | ISRCTN64926597 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64926597 |
| Secondary identifying numbers | CPMS 33945 |
- Submission date
- 22/05/2017
- Registration date
- 06/06/2017
- Last edited
- 20/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Diabetic foot ulcers (DFU) are a complication of diabetes mellitus, a lifelong condition that causes high or uncontrolled blood sugar. In the UK, DFUs affect about 2.5% of people with diabetes. If a DFU takes a long time to heal there is more chance of developing other complications such as infection. This can mean more hospital visits and can impact daily life. These are called ‘chronic’ or ‘hard to heal’ diabetic foot ulcers. The NHS has different treatment choices for hard-to-heal diabetic foot ulcers. The usual treatment involves wearing special footwear to reduce pressure on the ulcer, removing hard skin, and bandaging the ulcer. Some of the other treatment options include: hydrosurgical debridement (HD) which uses a stream of water to help take away the dead skin, decellularised dermal allograft (DCD) which is a skin graft from donated human skin applied to the ulcer and negative pressure wound therapy (NPWT) that uses dressing on the ulcer that is attached a pump to suck away any fluid. The aim of this study is to find out the best combination of treatments to use to help DFUs heal more quickly by measuring the size of the ulcer and comparing the healing to the different treatment options.
Who can participate?
Adults aged 18 years and older who have diabetes mellitus and a DFU.
What does the study involve?
Participants are randomly allocated to one of four groups, which may contain one, all, or a combination of the treatments. Those in the first group receive the treatment as usual (TAU). Those in the second group receive TAU plus HD. Those in the third group receive TAU, HD, DCD. Finally, those in the last group receive all four treatments (TAU, HD, DCD, NPWT). The wounds are checked in the clinic one week after the treatment has been given. Participants also attend visits at 2, 4, 8, 12, 20 and 52 weeks after the treatment has been given. At some of these visits ulcers are measured again by tracing it onto a clear sheet. Photographs are taken of the foot and participants are asked to fill out some short questionnaires. If the ulcer heals in between these visits, the research team checks the ulcer in the diabetic foot clinic. The treatment options that show the greatest improvement in the DFUs will be continued in another phase of this study and are again compared to the TAU group.
What are the possible benefits and risks of participating?
Participants may benefit from improvements in healing their foot ulcers. Participants may experience pain during the treatments and dressing changes, as well as infection and skin irritation. There is a small risk of increased bleeding with the HD treatment, as well as a small risk of allergic reaction and fluid build-up with DCD.
Where is the study run from?
This study is being run by the University of Leeds (UK) and takes place in hospitals with diabetic foot ulcer clinics across the UK
When is the study starting and how long is it expected to run for?
April 2017 to February 2025
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Miss Rachael Gilberts
r.m.gilberts@leeds.ac.uk or midfut@leeds.ac.uk
Contact information
Public
Clinical Trials Research Unit (CTRU)
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
| Phone | +44 (0)113 343 1724 |
|---|---|
| r.m.gilberts@leeds.ac.uk |
Scientific
Deputy TPD Vascular Surgery, Health Education Yorkshire and Humber
Leeds Vascular Institute
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom
 ORCID ID |
0000-0002-1293-5618 |
|---|---|
| Phone | +44 (0)7803 938880 |
| davidrussell1@nhs.net |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Device |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Multiple Interventions of Diabetic Foot Ulcer Treatment trial |
| Study acronym | MIDFUT |
| Study hypothesis | The aim of this study is to assess the use of hydrosurgical debridement alone or in combination with negative pressure would therapy and/or decellularised dermal allograft in the treatment of hard to heal diabetic foot ulcers. These health technologies and their use will be compared in combination to treatment as usual. |
| Ethics approval(s) | Yorkshire and The Humber Bradford Leeds Research Ethics Committee, 26/04/2017, ref: 17/YH/0055 |
| Condition | Diabetes mellitus |
| Intervention | Current interventions as of 10/12/2019: Phase II: Participants are randomly allocated to one of five four groups, which may contain one, all, or a combination of the treatments. The treatments include: Treatment as usual (TAU): Everyone receives TAU. This involves checking the ulcer often in the diabetic foot ulcer clinic and with the community team and helping to reduce pressure on the ulcer. This may include using special footwear to help reduce pressure when standing or walking. Any hard skin is removed and appropriate bandages or dressings are applied in the clinic and at home. Advice about how to look after the ulcer and diabetes management is also given. Hydrosurgical debridement (HD): This uses a machine called ‘VERSAJET’. VERSAJET uses a stream of water to help take away dead skin. It is used once on the ulcer in the diabetic foot ulcer clinic. Decellularised dermal allograft (DCD): This is a type of skin graft. It is made from donated human skin with all human cells removed. It is applied once to the ulcer at the diabetic foot ulcer clinic. Negative pressure wound therapy (NPWT): This uses a dressing on the ulcer covered with a waterproof layer. The dressing is attached to a pump which sucks fluid away from the ulcer. This is left in place for 2 weeks (but the dressing is changed during this time). Participants are randomly allocated on a 2:1:1:1:1 basis to receive the following treatment strategies; Group 1: Treatment as usual (TAU) Group 2: TAU + hydrosurgical debridement (HD) Group 3: TAU + HD + decellularised dermal allograft (DCD) Group 4: TAU + HD + DCD + NPWT The randomised treatment strategy is applied once at the baseline visit on the day of randomisation, however the NPWT remains in place for two weeks. The wounds are checked in the clinic one week after the treatment has been given. Follow up assessments takes place at 1, 2, 4, 8, 12, 20 and 52 weeks. At some of these visits ulcers are measured again by tracing it onto a clear sheet. Photographs are taken of the foot and participants are asked to fill out some short questionnaires. If the ulcer heals in between these visits, the research team checks the ulcer in the diabetic foot clinic. Phase 3: The intervention arms showing greatest evidence of efficiency in Phase II as well as the comparison arm (TAU) continue into Phase III. Participants are randomised on a 1:1:1 basis to one of the groups. The same processes are repeated as the second phase. _____ Previous interventions: Phase II: Participants are randomly allocated to one of five groups, which may contain one, all, or a combination of the treatments. The treatments include: Treatment as usual (TAU): Everyone receives TAU. This involves checking the ulcer often in the diabetic foot ulcer clinic and with the community team and helping to reduce pressure on the ulcer. This may include using special footwear to help reduce pressure when standing or walking. Any hard skin is removed and appropriate bandages or dressings are applied in the clinic and at home. Advice about how to look after the ulcer and diabetes management is also given. Hydrosurgical debridement (HD): This uses a machine called ‘VERSAJET’. VERSAJET uses a stream of water to help take away dead skin. It is used once on the ulcer in the diabetic foot ulcer clinic. Decellularised dermal allograft (DCD): This is a type of skin graft. It is made from donated human skin with all human cells removed. It is applied once to the ulcer at the diabetic foot ulcer clinic. Negative pressure wound therapy (NPWT): This uses a dressing on the ulcer covered with a waterproof layer. The dressing is attached to a pump which sucks fluid away from the ulcer. This is left in place for 2 weeks (but the dressing is changed during this time). Participants are randomly allocated on a 2:1:1:1:1 basis to receive the following treatment strategies; Group 1: Treatment as usual (TAU) Group 2: TAU + hydrosurgical debridement (HD) Group 3: TAU + HD + negative pressure wound therapy (NPWT) Group 4: TAU + HD + decellularised dermal allograft (DCD) Group 5: TAU + HD + DCD + NPWT The randomised treatment strategy is applied once at the baseline visit on the day of randomisation, however the NPWT remains in place for two weeks. The wounds are checked in the clinic one week after the treatment has been given. Follow up assessments takes place at 1, 2, 4, 8, 12, 20 and 52 weeks. At some of these visits ulcers are measured again by tracing it onto a clear sheet. Photographs are taken of the foot and participants are asked to fill out some short questionnaires. If the ulcer heals in between these visits, the research team checks the ulcer in the diabetic foot clinic. Phase 3: The two intervention arms showing greatest evidence of efficiency in Phase II as well as the comparison arm (TAU) continue into Phase III. Participants are randomised on a 1:1:1 basis to one of the groups. The same processes are repeated as the second phase. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Phase II: Reduction in index ulcer area size is calculated using wound tracing grid and image J software measurements at baseline and week four. Phase III: Time to healing is the length of time from randomisation to the date the index ulcer is confirmed as healed by the blinded assessor. |
| Secondary outcome measures | Phase II: There are no secondary outcome measures: Phase III: 1. Healing status of the index ulcer is measured by clinical assessment at week two, four, 12, 20 and 52 2. Incidence of infection according to IDSA criteria will be recorded at week two, four, 12, 20 and 52 3. Time to re-ulceration following healing will be measured as the date the index ulcer is confirmed as healed by a blinded assessor to the date re-ulceration is confirmed by a blinded assessor 4. Quality of life is measured using the DFS-SF and the EQ-5D-5L questionnaires at week four, 12, 20, and 52 weeks post randomisation 5. Hospital admissions and amputations are measured using patient records at week four, 12, 20, 52 post randomisation 6. Cost effectiveness is measured using a health resource utilisation questionnaire at week four, 12, 20 and 52 post randomisation |
| Overall study start date | 01/04/2017 |
| Overall study end date | 28/02/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 447; UK Sample Size: 447 |
| Total final enrolment | 213 |
| Participant inclusion criteria | Current inclusion criteria as of 15/02/2022: 1. Aged ≥18 years 2. Diagnosis of Diabetes Mellitus (according to WHO criteria) 3. Has a chronic DFU or surgical debridement wound or open minor amputation and in the opinion of the attending clinical team is not on a healing trajectory despite usual best care for a minimum of 4 weeks since initial presentation at the MDT DFU service* 4.1 Ankle brachial index for the leg of the index ulcer ≥0.7 or non-compressible (measurements available in the participants notes taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred), OR 4.2 Toe brachial index ≥0.5 or opening toe pressure ≥50mmHg or non-compressible 5. Expected to comply with the treatment strategies and follow up schedule 6. Consent to foot and wound photography 7. Consent to participate (written/witnessed verbal informed consent) *Defined as failure to achieve >50% reduction in index ulcer area over a minimum of 4 weeks using local wound measurement policies _____ Previous inclusion criteria as of 10/12/2019: 1. Aged ≥18 years 2. Diagnosis of Diabetes Mellitus (according to WHO criteria) 3. Has a chronic DFU or surgical debridement wound or open minor amputation and in the opinion of the attending clinical team is not on a healing trajectory despite usual best care for a minimum of 4 weeks since initial presentation at the MDT DFU service* 4. Ankle brachial index for the leg of the index ulcer ≥0.7 or non-compressible (measurements available in the participants notes taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred) 5. Expected to comply with the treatment strategies and follow up schedule 6. Consent to foot and wound photography 7. Consent to participate (written/witnessed verbal informed consent) *Defined as failure to achieve >50% reduction in index ulcer area over a minimum of 4 weeks using local wound measurement policies _____ Previous inclusion criteria as of 22/11/2018: 1. Aged ≥18 years 2. Diagnosis of Diabetes Mellitus (according to WHO criteria) 3. Has a chronic DFU or surgical debridement wound or open minor amputation defined by either (a) OR (b) below: 3(a). Duration of ≥ 12 weeks since initial presentation at the MDT DFU clinic and in the opinion of the attending clinical team is considered not to be on a healing trajectory despite usual best care† 3(b). Having <50% reduction in index ulcer area during a minimum period of 4 weeks prior to randomisation* 4. The index DFU has an area ≥0.8cm2 5. Ankle brachial index for the leg of the index ulcer ≥0.7 or non-compressible (measurements available in the participants notes taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred) 6. Expected to comply with the treatment strategies and follow up schedule 7. Consent to foot and wound photography 8. Consent to participate (written/witnessed verbal informed consent) † Participants who are eligible for randomisation under inclusion criteria 3(a) can be registered and randomised on the same day * Participants who are eligible for randomisation under inclusion criteria 3(b) will be randomised after a minimum 4 week suitability assessment period _____ Previous inclusion criteria from 07/09/2018 to 22/11/2018: 1. Aged ≥18 years 2. Diagnosis of Diabetes Mellitus (according to WHO criteria) 3. Has a chronic DFU or surgical debridement wound or open minor amputation defined as having <50% reduction in index ulcer area during a minimum period of 4 weeks prior to randomisation 4. The index DFU has an area ≥0.8cm2 5. Ankle brachial index ≥0.7 or non-compressible (measurements available in the participants notes taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred) 6. Expected to comply with the treatment strategies and follow up schedule 7. Consent to foot and wound photography 8. Consent to participate (written/witnessed verbal informed consent) Original inclusion criteria: 1. Aged ≥18 years 2. Diagnosis of Diabetes Mellitus (according to WHO criteria) 3. Has a chronic DFU or surgical debridement wound or open minor amputation defined as having <40% reduction in index ulcer area in the preceding ≥ 4 weeks prior to randomisation 4. The index DFU has an area ≥1cm2 5. Ankle brachial index ≥0.7 or non-compressible (measurements available in the participants notes taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred) 6. Expected to comply with the treatment strategies and follow up schedule 7. Consent to foot and wound photography 8. Consent to participate (written/witnessed verbal informed consent) |
| Participant exclusion criteria | Current exclusion criteria as of 15/09/2017: 1. Has any current clinically infected DFU on the foot of the index ulcer (as per IDSA guidelines) 2. HbA1C> 110mmol/mol (measurements available in the participants notes taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred) 3. Estimated glomerular filtration rate (eGFR) < 20mL/min/1.73m2 4. Index ulcer duration > 2 years (measurements taken within 3 months of randomisation can be used if no change in intervention or vascular events have occurred) 5. Planned or previous treatment with corticosteroids to an equivalent dose of prednisolone > 10mg per day or other immunosuppressive/immunomodulating therapy within 4 weeks prior to randomisation 6. Has evidence of connective tissue disorders as a cause of ulceration (e.g. vasculitis or rheumatoid arthritis) 7. Has evidence of dermatological disorders as a cause of ulceration (e.g. pyoderma gangrenosum or epidermolysis bullosa) 8. Planned or previous growth factor treatment within 4 weeks prior to randomisation 9. Planned or previous revascularisation or foot surgery affecting healing within the 4 weeks prior to randomisation 10. Index ulcer base has bone or joint involvement 11. Previously received DCD for the index ulcer within 4 weeks prior to randomisation 12. Previously received NPWT for the index ulcer within 4 weeks prior to randomisation 13. Previously received hydrosurgical or surgical debridement for the index ulcer within 4 weeks prior to randomisation 14. Has previously been randomised to the MIDFUT study 15. Unable to receive one or more of the randomised treatment strategies for any reason at the discretion of the attending clinical team (e.g. risk of excessive bleeding, serious falls risk, known allergies to NPWT dressings or dCELL dermis preparation components) Previous exclusion criteria: 1. Has any current clinically infected DFU (as per IDSA guidelines) 2. HbA1C> 110mmol/mol 3. Estimated glomerular filtration rate (eGFR) < 20mL/min/1.73m2 4. Index ulcer duration > 2 years 5. Planned or previous treatment with corticosteroids to an equivalent dose of prednisolone > 10mg per day or other immunosuppressive therapy within 4 weeks prior to randomisation 6. Has evidence of connective tissue disorders (e.g. vasculitis or rheumatoid arthritis) and has planned or is under active treatment 7. Has evidence of dermatological disorders as a cause of ulceration (e.g. pyoderma gangrenosum or epidermolysis bullosa) 8. Planned or previous growth factor treatment within 4 weeks prior to randomisation 9. Planned or previous revascularisation or foot surgery affecting healing within the 4 weeks prior to randomisation 10. Index ulcer base has bone or joint involvement 11. Previously received DCD for the index ulcer within 4 weeks prior to randomisation 12. Previously received NPWT for the index ulcer within 4 weeks prior to randomisation 13. Previously received hydrosurgical or surgical debridement for the index ulcer within 4 weeks prior to randomisation 14. Has previously been randomised to the MIDFUT study 15. Lacks mental capacity and is unable to provide informed consent |
| Recruitment start date | 01/10/2017 |
| Recruitment end date | 31/08/2023 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Leeds Teaching Hospitals NHS Trust
Leeds
LS9 7TF
United Kingdom
Kayll Road
Sunderland
SR4 7TP
United Kingdom
Pensnett Road
Dudley
DY1 2HQ
United Kingdom
Truro
TR1 3HD
United Kingdom
Blackshaw Road
London
SW17 0QT
United Kingdom
Bath
BA1 3NG
United Kingdom
Reading
RG1 5AN
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Salford
M6 8HD
United Kingdom
Ethelbert Road
Canterbury
CT1 3NG
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Norwich
NR4 7UY
United Kingdom
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Vicarage Lane
Fulwood
Preston
PR2 8DW
United Kingdom
York
YO31 8HE
United Kingdom
Coventry
CV2 2DX
United Kingdom
Govan Road
Glasgow
G51 4TF
United Kingdom
Watford Road
Harrow
HA1 3UJ
United Kingdom
SK2 7JE
United Kingdom
BH7 7DW
United Kingdom
Mellor House
Corporation St
Stafford
ST16 3SR
United Kingdom
110-120 Upper Pemberton
Kennington
Ashford
TN25 4AZ
United Kingdom
Chadwick Drive
Braintree
CM7 2AL
United Kingdom
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom
50 Frederick Street
Aberdeen
AB24 5HY
United Kingdom
Sandford Road
Cheltenham
GL53 7AN
United Kingdom
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom
London Road
Buxton
SK17 9NJ
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Sponsor information
Hospital/treatment centre
Research and Innovation Department
Research and Innovation Centre
St James’s University Hospital
Beckett Street
Leeds
LS9 7TF
England
United Kingdom
| Phone | +44 (0)113 206 0483 |
|---|---|
| anne.gowing@nhs.net | |
"ROR" |
https://ror.org/00v4dac24 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication of a monograph in NIHR journals and main trial results and associated papers in high-impact peer reviewed journals. |
| IPD sharing plan | De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance). Data will be made available at the end of the trial, i.e. usually when all primary and secondary endpoints have been met and all key analyses are complete. Data will remain available from then on for as long as CTRU retains the data. CTRU makes data available by a 'controlled access' approach. Data will only be released for legitimate secondary research purposes, where the Chief Investigator, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (in terms of scientific rigour and information governance and security), and that there are resources available to satisfy the request. Data will only be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject. No individual participant data will be released before an appropriate agreement is in place setting out the conditions of release. The agreement will govern data retention, usually stipulating that data recipients must delete their copy of the released data at the end of the planned project. The CTRU encourages a collaborative approach to data sharing, and believe it is best practice for researchers who generated datasets to be involved in subsequent uses of those datasets. Recipients of trial data for secondary research will also receive data dictionaries, copies of key trial documents and any other information required to understand and reuse the released datasets. The conditions of release for aggregate data may differ from those applying to individual participant data. Requests for aggregate data should also be sent to the above email address to discuss and agree suitable requirements for release. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 19/04/2020 | 19/10/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol (other) | Diabetic foot ulcer photography study: a study within a trial to assess the reliability of two-dimensional (2D) photography for the assessment of ulcer healing in patients with diabetes-related foot ulcers-protocol paper | 09/01/2025 | 20/01/2025 | No | No |
Editorial Notes
20/01/2025: A protocol for a study within a trial was added.
08/10/2024: The intention to publish date was updated from 30/06/2025 to 01/04/2025.
26/09/2023: Total final enrolment added. North Tees and Hartlepool Hospitals NHS Foundation Trust, Derbyshire Community Health Services NHS Foundation Trust and Manchester University NHS Foundation Trust were added as study participating centres.
16/08/2023: The intention to publish date was updated from 15/03/2025 to 30/06/2025.
19/10/2022: Publication reference added and intention to publish date updated from 30/04/2022 to 15/03/2025.
27/06/2022: The IPD sharing statement was added.
15/02/2022: The following changes were made to the trial record:
1. The overall end date was changed from 28/02/2024 to 28/02/2025.
2. The inclusion criteria were changed.
3. The recruitment end date was changed from 31/08/2022 to 31/08/2023.
4. The trial participating centre Gloucestershire Hospitals NHS Foundation Trust was added.
5. The plain English summary was updated to reflect these changes.
04/09/2020: The following changes were made to the trial record:
1. The target number of participants was changed from Planned Sample Size: 660; UK Sample Size: 660 to Planned Sample Size: 447; UK Sample Size: 447
2. The recruitment end date was changed from 30/09/2020 to 31/08/2022.
3. The recruitment resumed.
15/04/2020: The following changes were made to the trial record:
1. Due to current public health guidance, recruitment for this study has been paused.
2. The overall trial end date was changed from 31/03/2022 to 28/02/2024.
3. The trial participating centres were updated to remove The Pennine Acute Hospitals NHS Trust and add Provide CIC, Guy's & St Thomas NHS Foundation Trust, Blackpool Teaching Hospitals NHS Foundation Trust, and NHS Grampian.
10/12/2019: The following changes were made to the trial record:
1. The trial website was added.
2. The interventions were changed.
3. The inclusion criteria were changed.
4. The trial participating centres "Stockport NHS Foundation Trust, Royal Bournemouth Hospital NHS Trust, Midlands Partnership NHS Foundation Trust, Kent Community NHS Foundation Trust" were added.
5. The trial participating centres "Pinderfields Hospital, East Sussex Healthcare, Calderdale and Huddersfield NHS Foundation Trust" were removed.
03/04/2019: The condition has been changed from "Specialty: Diabetes, Primary sub-specialty: Both; UKCRC code/ Disease: Metabolic and Endocrine/ Diabetes mellitus" to "Diabetes mellitus" following a request from the NIHR.
6. The plain English summary was updated to reflect these changes.
05/03/2019: University Hospital Coventry and Warwickshire NHS Trust, NHS Greater Glasgow & Clyde, and London North West Healthcare were added as trial participating centres.
22/11/2018: The inclusion criteria were updated and the following sites were added: Oxford University Hospitals NHS Foundation Trust, Lancashire Care NHS Foundation Trust, York Teaching Hospital NHS Foundation Trust.
07/09/2018: The inclusion criteria were updated and the following sites were added: East Kent Hospitals University NHS Foundation Trust, Hull and East Yorkshire Hospitals NHS Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, Calderdale and Huddersfield NHS Foundation Trust.
02/05/2018: The following sites have been added: The Pennine Acute Hospitals NHS Trust, East Sussex Healthcare NHS Trust and Salford Royal NHS Foundation Trust.
16/03/2018: The following sites have been added: Royal United Hospital Bath NHS Foundation Trust, Royal Berkshire Hospital and The Royal Free Hospital. Wythenshaw Hospital has been removed.
15/12/2017: The following sites have been added: Sunderland Royal Hospital, Wythenshaw Hospital, Russells Hall Hospital, Royal Cornwall Hospital, St George’s University Hospital and Pinderfields Hospital.
15/09/2017: Tameside General Hospital, Bradford Royal Infirmary, Salford Royal Hospital, Hull Royal Infirmary, and Royal Free Hospital have been removed as trial participating sites. Inclusion and exclusion criteria have been updated.
