EXamining antibiotics for ulCerated skIn cancer Surgical Excision (EXCISE)

RESEARCH QUESTION: Is oral flucloxacillin effective in preventing surgical site infection (SSI) in adults who have undergone surgical excision of an ulcerated skin cancer under local anaesthesia?

BACKGROUND: Skin cancers are common with a lifetime risk of 1 in 5 in the UK. Surgical removal is the first line treatment for skin cancers and SSI is a complication of surgery. Oral antibiotics are often prescribed for skin cancer surgery – particularly if the skin cancer is ulcerated – to reduce the risk of SSI. However, to date there is no robust evidence to guide the need for oral antibiotics.

AIMS: To compare the clinical and cost effectiveness of oral flucloxacillin versus no antibiotic (placebo) in adults undergoing ulcerated skin cancer excision under local anaesthetic with planned wound closure.

METHODS: Randomised, double-blind, superiority placebo-controlled trial (with internal pilot). 380 adult patients undergoing surgical excision of ulcerated skin cancer in UK NHS hospitals will be individually randomised to oral flucloxacillin 1g (500mg x 2) pre-operatively. Patients will be followed up by telephone at 5-10 days, 15-20 days and at 30 days.

All participants will be asked to monitor their wounds for infection, and should they develop any symptoms suggestive of infection then they will be asked to contact their local recruiting centre to arrange an in-person clinical assessment.

OUTCOMES: The primary outcome will be SSI (using Centers for Disease Control and Prevention criteria) within 30 days. Clinical assessors will be trained in the diagnosis of wound infections and be blinded to the randomised allocation. Secondary outcomes are: adverse events within 30 days; antibiotic resistance in wounds at diagnosis of SSI and after 7 days if no response to treatment; quality of life measured by EQ-5D-5L at 30 days and 3 months; time to return to normal activity/work at 30 days and 3 months, resource use (related to wound complications including SSI); cost of hospital visits/stays and feasibility of ‘Selfi-wound’ photos.

We will also explore patient wound burden as a tertiary outcome. A qualitative process evaluation of acceptability, facilitators and barriers will be conducted with patients and healthcare professionals. TIMELINES: informed by our feasibility trial: Month 1-9: Study set-up, contracts, regulatory approvals, Investigational Medicinal Product manufacture.

Month 10-15: Internal pilot, site set-up and recruitment. Month 16: Review of internal pilot. Month 16-24: Complete recruitment. Month 30: Last participant last follow-up. Month 31-36: Data cleaning, analysis, prepare papers and report; stakeholder event. ANTICIPATED IMPACT AND DISSEMINATION:

We anticipate EXCISE will provide high-quality evidence for the clinical and cost effectiveness of peri-operative oral flucloxacillin before surgery for ulcerated skin cancers, helping to inform patients, carers and clinicians, mitigate inappropriate prescribing and standardise clinical practice. We will hold a multi-stakeholder event to ensure findings are widely disseminated and translated into NHS clinical practice.

Patient-facing documents will be circulated via charities and other national organisations e.g, UK Dermatology Clinical Trials Network. Results will inform national and international guidelines for skin surgery.