Developing and Evaluating A Multifactorial Intervention to Improve Cardiovascular Outcomes in Adults with Type 2 Diabetes and Current or Previous Diabetic Foot Ulcers (MiFoot)

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.