Award Title: Developing and Evaluating A Multifactorial Intervention to Improve Cardiovascular Outcomes in Adults with Type 2 Diabetes and Current or Previous Diabetic Foot Ulcers (MiFoot)
Funder: Department of Health and Social Care

Abstract: Research questions:    Is there geographic and demographic variation in outcomes in people with type 2 diabetes (T2D) and diabetic foot ulcer disease (DFUD), such as cardiovascular disease (CVD), mortality, and amputation?  Which risk factors explain the excess risk of CVD specific to DFUD?  Which elements of previous interventions in people with DFUD are effective?  Can a complex intervention aimed at medication optimisation and behaviour change be effective, cost-effective and sustainable in preventing CVD events in people with DFUD?      Background:  Individuals with T2D and DFUD (~50-60,000 in the UK) have CVD much in excess of those with T2D alone. CVD is the leading cause of death in this group, but interventions to reduce event rates have not been developed or tested. Traditional CVD interventions may not be appropriate for this high-risk population; for example, weight-bearing physical activity and some glucose lowering medications are contraindicated in DFUD. An evidence-based CVD prevention intervention for people with T2D and DFUD is a significant unmet patient need.     Aim: Reduce CVD events (including mortality) in adults with T2D and current/previous DFUD.     Objectives:    Evaluate risk of worsening morbidity or mortality in DFUD  Evaluate existing interventions to reduce CVD risk in DFUD  Develop a multifactorial complex intervention to prevent CVD events in T2D and DFUD  Evaluate the intervention s effectiveness, cost-effectiveness and sustainability      Methods:  There will be four workstreams (WSs), with PPI/E integrated throughout.  WS1: Analyse routinely-collected primary and secondary care data to understand the healthcare needs, disease burden and sociodemographic/geographic factors associated with DFUD, and estimate the incidence of CVD-related events and mortality.  WS2: Perform a systematic review, meta-analysis and mixed treatment comparison of existing interventions for people with DFUD. We can then use evidence about what has, and has not, worked well before to design our intervention.  WS3: Develop a complex intervention to reduce CVD events in people with T2D and DFUD by combining patient and healthcare professional views (qualitative study), findings from WS1 and WS2, PPI/E input, and our in-depth experience. It will likely use one-to-one, group and online sessions to target medication optimisation and behaviour change, including seated exercise. We will estimate the expected economic benefit of intervention implementation.  WS4: Perform a randomised controlled trial, informed by previous WSs, with internal feasibility study and process evaluation to test the intervention effectiveness (an extended Major Adverse Cardiovascular Event [MACE] composite as primary outcome) and cost-effectiveness for preventing CVD events. Participants (n=392) will be randomised 1:1 to intervention or control conditions.     Delivery timelines:  PPI: Pre-funding to post-funding (Deliverable: Month 63)   WS1 and WS2: Months 1-12   WS3: Pre-funding to month 39   WS4: Months 4-63 (including setup)   Dissemination: Primarily months 13-24, 40-52 and 60 onwards.     Anticipated Impact and Dissemination:  The primary impact, if achieved, will be a substantial reduction in CVD outcomes for those with DFUD. Academic and non-academic outputs will be disseminated through well-established methods, including press releases, social networks, open days, and relevant charities. Wider effects include improved disease self-management ability and quality of life. These benefits will likely translate to economic benefits for the NHS.

Lay Abstract: Problem   Type 2 diabetes (T2D) can lead to heart attack, stroke, and early death. The risk of these is increased in people with T2D who have had diabetic foot ulcer disease (DFUD). In the UK, 50,000-60,000 people have DFUD, which are slow healing wounds on the foot that may lead to amputation and disability.  Aim   Reduce the very high risk of heart disease, stroke and early death in people with T2D and current/previous DFUD, so that the risk is similar to people with T2D who have not had DFUD.      Research plan    1: Use digital data that is routinely collected during patient care (including demographics, medical history, medications) from GP and hospital records to understand healthcare needs of people with current/previous DFUD. We will look at how many people with DFUD and T2D have heart disease, stroke and early death, and whether certain groups are at greater risk than others.      2: Conduct a detailed review of existing interventions to find out what has, and has not, worked well before.      3: Combine 1 and 2, with PPI/E input and our own experience to develop a care package (MiFoot) to reduce heart attacks, stroke and early death in people with T2D and current/previous DFUD. MiFoot will likely include one-to-one, group, and online sessions. It will also help people to exercise while sitting, manage their medicines, and support their wellbeing and fitness.      4: Test if MiFoot prevents heart attacks, strokes and early death, and is good value for money, through a randomised controlled trial comparing MiFoot with usual care.      How we will involve patients   Discussions with people with T2D and their carers formed the basis of the initial MiFoot design, as well as important parts of the study design and this application (such as this summary). The team includes an expert by experience, who reviewed the application.      We will recruit a patient/carer panel of 15 people with T2D and current/previous DFUD to meet at least monthly. The meetings will be led by panel members and will support development of a best practice guide for PPI/E with people with T2D and current/previous DFUD. Panel members will be involved in developing MiFoot and making sure that the trial is acceptable for participants. We will work to ensure that panel members are consulted and involved throughout the research and receive adequate training. PPI/E costs have been included.      What we will do with the results   We will share findings with people living with diabetes, public, health care professionals, and NHS decision-makers. The PPI/E panel and our Centre for Ethnic Health will advise on the best ways to reach patients. This will include engaging with local/national press and charities (including Diabetes UK), social networks, open days, and a website.

Research Activity Codes: 6.1 PHARMACEUTICALS;6.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.7 PHYSICAL
Health Categories: CARDIOVASCULAR;METABOLIC AND ENDOCRINE