Title: A randomised controlled trial of compression therapies for the treatment of venous leg ulcers.
Funder: Department of Health and Social Care

Abstract: Venous leg ulcers are common, open wounds that are painful and reduce health-related quality of life. These wounds are caused by damage in the leg veins which stops blood flowing properly and leads to tissue break down and poor healing. _x000D_ _x000D_ We know that wrapping four layers of bandages (called compression bandages) tightly round affected legs improves blood flow and helps to heal venous leg ulcers. It is important that these four-layer bandages are applied by a trained health care professional because they don’t work if applied too loosely and are dangerous if too tight. _x000D_ _x000D_ The four-layer bandages take time to put on and need to be changed at least once a week. Some people don’t like wearing the bandages because they find them bulky and uncomfortable. To help two-layer hosiery (below-knee stockings) have been developed – these are thinner than four layers of bandages, can be applied by patients and/or carers and may be more comfortable. Our research has shown that ulcers treated with the four-layer bandage or with two-layer hosiery take a similar time to heal. However, on average, people using hosiery were less likely to have their ulcer come back and the hosiery was shown to save the NHS money. Not all people can use hosiery though so together patients and health professionals choose the best option. Both the four-layer bandage and two-layer hosiery are “evidence-based compression”. _x000D_ _x000D_ Two new compression treatments are being used in the NHS in addition to evidence-based compression. The first is the two-layer bandage and the second is adjustable hook-and-loop-fastened compression systems (we call these compression wraps). There is a lot of interest in these treatments but we do not know if they work as well as evidence-based compression as they have not been properly tested. _x000D_ _x000D_ We want to test these three main compression treatments:_x000D_ • evidence-based compression (choice of four-layer bandage or two-layer compression hosiery);_x000D_ • two-layer bandage;_x000D_ • adjustable hook-and-loop fastened compression systems (“compression wraps” )_x000D_ _x000D_ In our study people with a venous leg ulcer will be treated with one of the three treatments (the treatment they receive will be decided by a computer – we call this randomisation). Working with several clinical centres we will collect data on how quickly ulcers heal when they are treated, as we know this is the outcome that patients value most. We will also collect data on if and when people get ulcers again, how safe the treatments are and the costs of treating people in all the groups. The research team consists of trial experts, statisticians, health economists, doctors and nurses who work in the field. This team has successfully carried out many similar studies.

Lay abstract: Background: Compression is an effective treatment for reducing the time to healing of venous leg ulcers. There are three main full compression treatments: _x000D_ _x000D_ 1. Evidence-based compression (EBC: composed of two-layer hosiery or four layer bandages); _x000D_ 2. Two-layer bandages and _x000D_ 3. Adjustable hook-and-loop-fastened compression (compression wraps). _x000D_ _x000D_ Only EBC has been well evaluated: this is the gold standard full compression treatment. Two-layer bandages, whilst relatively under-evaluated, are widely used to treat venous leg ulcers. Compression wraps are also untested but not widely used in venous leg ulcer care: these wraps may have potential advantages over bandages. _x000D_ _x000D_ Because of the varying effectiveness evidence for different compression bandage systems we propose a three arm trial to address treatment uncertainties around compression wraps in a way that is most relevant to decision makers. _x000D_ _x000D_ Aims and objectives: Our key objectives are:_x000D_ • to compare compression wraps with EBC in terms of the time to healing of venous leg ulcers;_x000D_ • to determine whether two-layer bandages are non-inferior to EBC for time to healing of venous leg ulcers;_x000D_ • to determine which is the most cost-effective, full compression treatment for venous leg ulcers; _x000D_ • to undertake at least two studies within a trial to aid recruitment and retention to the trial._x000D_ _x000D_ Methods: A multi-centre, three-arm, parallel group, pragmatic randomised controlled trial (with a nested internal pilot). The trial will have equal randomisation. Sample size is based on previous research and shows we need to recruit 675 participants with at least one venous leg ulcer. We will follow people up for a maximum of 12 months. Our primary outcome is time to ulcer healing. _x000D_ _x000D_ A mixed methods approach will be used to explore adherence to compression and underlying issues around this which may explain trial findings. _x000D_ _x000D_ Analysis: An intention to treat analysis will be conducted on time to healing and secondary outcomes including health related quality of life, adverse events, pain and time to recurrence. Healing data will be used to update our published network meta-analysis of full compression for venous leg ulcers. _x000D_ _x000D_ We will extend the trial findings by updating and expanding our current decision analytic model in this area. Using this model we will determine the most cost-effective full compression treatment for venous leg ulcers. _x000D_ _x000D_ Timelines for Delivery: The study is 48 months in duration (including a 6 month nested internal pilot). We have allowed 6 months for site set-up, 36 months for recruitment and follow-up and a subsequent 6 months for analyses and write-up. _x000D_ _x000D_ Dissemination and impact: The results of the study will be disseminated widely through our extensive existing networks. Continued and active work with these stakeholders as well as relevant quality improvement work, which we have developed successfully from our previous large compression trials, will also ensure dissemination is converted to impact. _x000D_ _x000D_ Patient and public involvement: Our Wounds Research Patient and Public Forum, which has 12 members, has informed the design and content of this study. Members will continue to comment on the design of the trial, its documentation, especially that to be read and completed by prospective participants, and dissemination of study results.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR