Cellulitis Optimal Antibiotic Treatment

Study Overview
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Brief Summary
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To determine whether a short course of oral flucloxacillin (5 days) is non-inferior to a standard course (7 days) in terms of pain over days 6-14 (indicative of persistence or recurrence associated with the symptoms of most importance to patients) in adults with cellulitis of the leg presenting in primary care.

Detailed Description
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Cellulitis is a deep infection of the skin and subcutaneous tissues and most often occurs in the legs. It is a painful condition that is associated with inflammation and swelling of the site, and often systemic symptoms such as fever, headache, muscle aches, malaise, and fatigue. Patients report feeling unwell and that it has a significant impact on their mobility and ability to carry out their usual activities. NICE guidelines recommend oral flucloxacillin 500-1000 mg four times daily for 5-7 days as first-line treatment for most patients with cellulitis in the community, but most prescriptions are dispensed for a 7-day course. We will be assessing the effectiveness and safety of a 5-day treatment vs. the standard 7-day treatment. We also aim to evaluate the cost-consequences of a shorter course from an NHS and personal perspective. Participants will be randomly allocated to one of two groups. In addition to usual care, participants will either be assigned to a 5-day oral flucloxacillin course or a standard 7-day flucloxacillin course. Participants will be prescribed a 5-day course of oral flucloxacillin, and two additional tablets will be posted to the participants which will either be the antibiotic or a placebo tablet. Participants will be asked to fill out daily questionnaires and express their experiences with the shortened course and taking part in the trial.

Official Title
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A Blinded, Non-inferiority Phase III Trial of 5 Versus 7 Days of Oral Flucloxacillin in Primary Care Patients With Lower Limb Cellulitis

Conditions
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Cellulitis of Leg

Intervention / Treatment
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* Drug: Flucloxacillin Only Product in Oral Dose Form
* Drug: Placebo Only Product in Oral Dose Form


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be aged 18 years or older Currently showing symptoms of cellulitis (such as pain, tenderness, redness, other change in skin color, warmth to touch) in one leg for 10 days or less Pain rated as 3/10 or higher on a numerical rating scale (0-10) at baseline assessment Be willing to be randomized to either trial arm (5-day or 7-day treatment) Able to complete trial procedures in the English language. Exclusion Criteria: Have penicillin allergy Have bilateral cellulitis Have had antibiotics for cellulitis within the past month Have post-operative cellulitis (within 30 days of operative procedures on the same leg) Have cellulitis resulting from human/animal bite injury Have Cellulitis associated with chronic (>6 weeks) leg ulceration Require immediate hospital admission or out-patient intravenous antibiotic therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A phase III blinded, multi-center, non-inferiority trial assessing the effectiveness and safety of 5 days vs 7 days of oral flucloxacillin 500mg QDS for lower leg cellulitis, and to evaluate the cost-consequences of a shorter course from an NHS and personal perspective. Participants will be recruited in NHS primary care settings in England and Wales. We will primarily recruit through general practices but will explore the possibility of recruiting through out-of-the-hours and urgent care settings.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Intervention<br>Flucloxacillin 500mg four times a day (QDS) for 5 days (unblinded NHS prescription) followed by blinded placebo QDS for 2 days (5 days of antibiotic) | Drug: Flucloxacillin Only Product in Oral Dose Form<br>* Patients will be prescribed flucloxacillin 500mg QDS for 5 days followed by blinded flucloxacillin 500mg for 2 days, reaching a total of 7 days of antibiotic treatment<br>Drug: Placebo Only Product in Oral Dose Form<br>* Patients will be prescribed flucloxacillin 500mg QDS for 5 days followed by a blinded placebo for 2 days, reaching a total of 5 days of antibiotic treatment<br>|
| Active Comparator: Control<br>Flucloxacillin 500mg QDS for 5 days (unblinded NHS prescription) followed by flucloxacillin 500mg QDS (blinded) for 2 days (7 days of antibiotic) | Drug: Flucloxacillin Only Product in Oral Dose Form<br>* Patients will be prescribed flucloxacillin 500mg QDS for 5 days followed by blinded flucloxacillin 500mg for 2 days, reaching a total of 7 days of antibiotic treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessment | Self-reported pain (measured using the Pain Numeric Rating Scale (0-10)) | Days 7-16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use of additional antibiotics | Any reported use of antibiotics other than the initial 5 days of flucloxacillin and 2 days of IMP) | Up to day 28 | 
| Patient-reported assessment of how well they are feeling | Numeric rating scale NRS (0-10) and assessed as repeated measures | Days 6-14 | 
| Health related quality of life | EQ-5D-5L - values, and individual dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) level scores using repeated measures. | Days 6-14 | 
| Health related quality of life used to estimate Quality Adjusted- Life Years (QALYs) | EQ-5D-5L - values, and individual dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) level scores using repeated measures. | Days 6-14 | 
| Leg swelling and warmth | Participant reported questionnaire | Day 7, 14, 21, 28 | 
| Time until self-reported recovery | Participant reported questionnaire | Day 7, 14, 21, 28 | 
| Time until self-assessed extent of cellulitis starts to reduce (with no subsequent increase) | Participant reported questionnaire | Day 7, 14, 21, 28 | 
| Hospital admissions | Number of hosptial admissions since randomisation, collected from primary care notes review | 12 months | 
| Recurrent cellulitis episodes over 12 months (number of episodes) | Recurrent cellulitis episodes over 12 months (number of episodes) since randomisation, collected from primary care notes review | 12 months | 
| Complications over 12 months | Number of reported complications since randomisation, collected from primary care notes review | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary care, Antibiotic treatment, Antibiotic resistance, Pain, Cost consequences