Condition category
Nutritional, Metabolic, Endocrine
Date applied
22/05/2017
Date assigned
06/06/2017
Last edited
15/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Diabetic foot ulcers (DFU) are a complication of diabetes mellitus, a condition that causes 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 on 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) that uses a stream of water to help take away the dead skin, decellualrised 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 and older who have diabetes mellitus and a DFU.

What does the study involve?
Participants are randomly allocated to one of five 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 receives TAU plus HD and NPWT. Those in the fourth 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 two 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 ulcer. 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 a diabetic foot ulcer clinic across the UK.

When is the study starting and how long is it expected to run for?
April 2017 to March 2022

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
1. Miss Rachael Gilberts (Public)
r.m.gilberts@leeds.ac.uk or midfut@leeds.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Rachael Gilberts

ORCID ID

Contact details

Clinical Trials Research Unit (CTRU)
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 113 343 1724
r.m.gilberts@leeds.ac.uk

Type

Scientific

Additional contact

Mr David Russell

ORCID ID

http://orcid.org/0000-0002-1293-5618

Contact details

Deputy TPD Vascular Surgery
Health Education Yorkshire and Humber
Leeds Vascular Institute
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom
+44 7803 938880
davidrussell1@nhs.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

33945

Study information

Scientific title

Multiple Interventions of Diabetic Foot Ulcer Treatment trial

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

Yorkshire and The Humber Bradford Leeds Research Ethics Committee, 26/04/2017, ref: 17/YH/0055

Study design

Randomised; Interventional; Design type: Treatment, Device

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Diabetes, Primary sub-specialty: Both; UKCRC code/ Disease: Metabolic and Endocrine/ Diabetes mellitus

Intervention

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

Other

Phase

Drug names

Primary outcome measures

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 trial start date

01/04/2017

Overall trial end date

31/03/2022

Reason abandoned

Eligibility

Participant 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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 660; UK Sample Size: 660

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

30/09/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St James’s University Hospital
Beckett Street Leeds Teaching Hospitals NHS Trust
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

The Leeds Teaching Hospitals NHS Trust

Sponsor details

Research and Innovation Department
Research and Innovation Centre
St James’s University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
+44 113 206 0483
anne.gowing@nhs.net

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

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 statement:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/04/2022

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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 has been updated. Internal review.