Title: Cellulitis Optimal Antibiotic Treatment: COAT study
Funder: Department of Health and Social Care

Abstract: Aim_x000D_ To see if a 5-day course of flucloxacillin (antibiotic taken by mouth) is as effective as a standard 7-day course in people with cellulitis of the leg in primary care. _x000D_ _x000D_ Background_x000D_ Cellulitis is an infection spreading into the deeper layers of the skin. It commonly occurs in the legs, especially in older people. NICE guidelines suggest that most people with cellulitis should be treated in primary care with the antibiotic flucloxacillin for 5-7 days (by mouth). However, almost all patients are treated for 7 days initially, possibly because there are no studies comparing 5 days of flucloxacillin with longer courses. _x000D_ _x000D_ There is evidence from studies that shorter courses (less than 7 days) of antibiotics are as effective as longer courses for several infections, including pneumonia, urinary infections, and sore throat/tonsillitis. Taking antibiotics for a shorter duration will mean fewer side effects and problems with antibiotic resistance. However, there have been very few studies that compare the effects of different durations of antibiotic treatment for cellulitis. _x000D_ _x000D_ Design and methods_x000D_ We will invite people to take part in the study when they see their GP and are found to have cellulitis affecting the leg. Those who agree to take part will be prescribed flucloxacillin tablets/capsules to take four times a day for 5 days. They will also be sent a pack containing medication to take on days 6 and 7. Half the people will be given placebo (dummy) tablets to take for the final 2 days (5 days of antibiotics in total) and the other half will be sent antibiotic tablets to take for the final 2 days (7 days of antibiotics in total). Patients will be put into these two groups at random and will not know which group they are in. If someone is getting worse while taking their study treatment their doctor will assess them and prescribe additional antibiotics if necessary. People taking part will be asked to report their pain, how unwell they are feeling, questions about their mobility, self-care and ability to do usual activities, and their use of medication, every day for 14 days using an online form with SMS (text) links, or by paper, supported by telephone calls. They will also be asked additional questions on days 7, 14, 21 and 28, and we will look for complications of cellulitis and recurrence by searching their GP record after 12 months. The main outcome will compare pain scores over days 6-14 in the two groups to make sure they are not worse in the 5-day antibiotic group. We will also compare other outcomes including, quality of life, how many people needed to take additional antibiotics, time until recovery, complications and need for hospital admission._x000D_ _x000D_ Patient and public involvement_x000D_ Six public contributors with lived experience of cellulitis have helped design this study and two are members of our study team and will be involved in study delivery if funded. One of their key influences has been the focus on pain as the most important outcome to people with cellulitis. We will also recruit a PPI reference group to help develop participant materials, assess study processes, and interpret findings._x000D_ _x000D_ Dissemination_x000D_ In addition to publishing our findings in a peer-reviewed journal, we will work with patient organisations, clinicians, and the NHS to ensure that the findings are put into practice and feedback findings to study participants.

Lay abstract: Research question: _x000D_ Is a short course (5d) of flucloxacillin non-inferior to a standard course (7d) in terms of pain over days 6-14, in patients with leg cellulitis in primary care?_x000D_ _x000D_ Background:_x000D_ Cellulitis is a common, and potentially serious, deep skin infection. It is particularly common in older people, and most commonly occurs in the legs. NICE recommend 5-7 days of the oral antibiotic flucloxacillin for most patients managed in primary care, but over 90% of patients are treated for 7 days or more. Shorter courses of antibiotics have been shown to be as effective as longer courses for many infections and have the potential to reduce adverse effects and the development of antimicrobial resistance. A small number of studies suggest that short courses are as effective as longer courses for cellulitis, but there have been no trials of short courses of oral flucloxacillin for cellulitis._x000D_ _x000D_ Aims and objectives: _x000D_ 1. Assess the effectiveness and safety of 5 days vs 7 days of flucloxacillin for lower leg cellulitis._x000D_ 2. Evaluate the cost-consequences of a shorter course from an NHS and personal perspective._x000D_ _x000D_ Methods:_x000D_ A blinded, non-inferiority trial comparing 5 vs 7 days of flucloxacillin. Participants will be adults presenting in primary care with unilateral leg cellulitis associated with a pain score of 3 or more. Participants will be prescribed flucloxacillin 500mg four times a day (QDS) for 5 days and sent a blinded study pack containing placebo QDS for 2 days (total 5d antibiotic) or flucloxacillin 500mg QDS for 2 days (total 7d antibiotic). Following baseline data collection participants will be asked to rate pain and how unwell they feel using numeric rating scores (0-10), complete EQ-5D, and report antibiotic and analgesic use daily for 14 days using a simple online form and daily SMS links (or paper diary) supported by phone calls. Additional questions on days 7, 14, 21 and 28 will include DLQI, leg tenderness and swelling, use of additional antibiotics, day extent of cellulitis starts to reduce, and day recovered. D28 questions will also include complications, healthcare consultations and costs. Recurrent episodes and long-term complications will be assessed by searching their GP record after 12 months. The primary outcome of pain over days 6-14 will be assessed using repeated measures and the between group difference compared to a non-inferiority margin of 1. Secondary outcomes include recurrent symptoms requiring additional antibiotics, feeling unwell, EQ5D, mobility, self-care, recovery complications and recurrence. Economic effects will be explored by a cost-consequences analysis over the 12-month horizon._x000D_ _x000D_ Timelines for delivery:_x000D_ Setup: m1-9_x000D_ Internal pilot: m10-15_x000D_ Participant recruitment: m10-29_x000D_ 28d follow-up complete: m30_x000D_ 28d follow-up analysis: m32-37_x000D_ 12m follow-up note searches: m30-42_x000D_ Final analysis and dissemination: m43-48_x000D_ _x000D_ Anticipated impact and dissemination:_x000D_ The results will inform the management of leg cellulitis in primary care and either support or reject a change to use of a 5-day course of flucloxacillin as standard treatment. If our findings support a change then this will lead to a meaningful reduction in overall antibiotic use, leading to reduced antimicrobial resistance and therefore benefit for patients. Evidence that 5-days is inferior will lead to increased certainty, changes to NICE guidance, and a change in treatment for the minority who currently receive a 5-day course.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION