Title: SHarp dEbridement of Digital ulcer in Systemic SClerosis (SHED SSc): a multicenter Randomised Control Trial feasibility study.
Funder: Health Education England

Abstract: Can a multicentre Randomised Control Trial assessing the effects of sharp-debridement on digital ulcers in patients with scleroderma be conducted? Digital Ulcers (DU) occur in around 50% of patients with scleroderma. DU are recurrent, painful and on average take 76 days to heal. Local treatment aims to increase healing and reduce complications, such as infection and amputation. Sharp-debridement has been suggested to aid DU healing; however, there is no evidence to support this. The aim of this study is to assess the feasibility of conducting a multicenter randomised controlled trial (RCT) to evaluate the effects of sharp-debridement on DUs in patients with scleroderma. The research objectives will assess: trial process and procedures i.e. recruitment strategy, randomisation, compliance, subjective and objective outcomes measures and intervention delivery; the willingness of clinicians to randomise participants, and of patients to be randomised; the feasibility of collecting the data required to undertake a trial-based economic evaluation.These objectives will be explored by undertaking an open-label multicentre feasibility RCT and a UK-wide survey to identify collaborative centres for a definitive RCT.Seventy patients with scleroderma and DUs will be randomised 1:1 to receive sharp-debridement plus standard wound-care (intervention arm) or standard wound-care only (control arm), and will be followed up for 24 weeks. For the intervention arm the follow-up visits during the active-debridement phase will be at 7 day intervals. Post-debridement phase, visits to receive standard wound care will be every 14 or 21 days, as per clinical judgment. For the control arm, the follow-up visits will be between 7 to 21 days, determined by the clinician. The feasibility outcomes for this study will be recruitment, retention, and concordance with allocation. Clinical outcomes will be: time-to-heal, ulcer status, infection, ulcer-related pain, treatment tolerability, physical function, quality of life, and health-care resources consumed. Analyses will be descriptive as recommended in the CONSORT extension for randomised pilot and feasibility trials. A Kaplan-Meier plot will display time-to-healing for the two groups and a median time-to-healing and 95% confidence interval will be presented.A UK-wide web-based survey will be undertaken to assess the willingness of other specialist centres to collaborate in the definitive RCT, and a Debridement Training Work Package (DTWP) will be developed to standardise the method of sharp-debridement delivery. The survey will be developed and undertaken during the six-month set-up trial period. An 18-month recruitment phase will follow, plus six months follow-up. During the first six month of the final year the DTWP will be developed and on the final six months data entry, analysis, write-up and dissemination will be accomplished. This feasibility study (if successful) will inform the design of a definitive RCT which will produce evidence-based data on DU treatment in patients with scleroderma. This will inform the development of a DU treatment pathway and improve clinical practice, contributing to the creation of a safer, higher quality health-care service for these patients. The results from this research will be shared through public and patient's forums, and professional channels such as conference presentations and journal publications.

Lay abstract: Scleroderma is a chronic disease that affects the immune system, blood flow, skin and internal organs. Around 50 % of patients with scleroderma suffer from ulcers (wounds) on the fingers and/or toes. These ulcers are caused by poor blood flow and tightening of the skin. Little is known about what treatments are effective in healing these ulcers. Research in other disease suggests that sharp debridement i.e removal of dead skin on or surrounding the ulcer(s) using a scalpel, could improve healing. However, in scleroderma- related ulcers, there is a lack of studies to support this approach. In addition, doctors have questioned the usefulness of this method to promote healing of scleroderma-related ulcers. Therefore, we are proposing to run a small scale study (feasibility study) which could inform us as to whether or not it is possible to conduct a larger, more expensive study (Randomised Controlled Trial) to investigate if removing dead skin from an ulcer helps healing. This small scale study comprises 70 patients with scleroderma -related ulcers on the fingers or/and toes. They will be randomly selected to receive either sharp-debridement and standard wound-care (treatment group) or standard wound-care only (control group) for the treatment of their ulcer(s) . These 70 patients will attend clinic appointments for a total of 24 weeks. During this period, a podiatrist or a nurse will provide the patient with the allocated ulcer treatment every 7, 14 or 21 days, depending on the progression of the ulcer's healing. The wound-care for the treatment group will be: wound cleaning, anesthetic cream (cream to numb the ulcer), sharp-debridement of the wound/s, and dressings. The patients also will receive information regarding wound-care, dressing change and ulcer infection. The other group will receive the same treatment without the sharp-debridement. Upon completion of the 24-week programme, all patients will receive routine wound care. The aim of the study is to assess the practicalities of running a large scale study. One of outcomes will be to assess if the patients want to remain in the sharp-debridement treatment group and to continue in the study. To assess the effects of the treatment from the patient's perspective, we will measure if the patients can tolerate the treatment and its effects on their quality of life. In addition, we will explore the possible effects of sharp-debridement on ulcer healing, by assessing healing rate (by measuring the wound surface area) and time-to-healing (in days). The costs involved in this treatment will also be calculated. Patients and service users who have contributed to the development of this study will be involved in the running of the study as part of the advisory panel. The results from this research will be shared through public and patient's forums, as well as through research and professional channels such conference presentations and journal publications. Results from this small scale study will inform the design of a future study.

Research activity codes: 6.4 SURGERY
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM