Cellulitis Optimal Antibiotic Treatment (COAT)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cellulitis of Leg
• Intervention / Treatment: Drug: Flucloxacillin Only Product in Oral Dose Form; Drug: Placebo Only Product in Oral Dose Form

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 356
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Intervention; 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; 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; Drug: Placebo Only Product in Oral Dose Form; 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
Active Comparator: Control; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Southampton
• Collaborators: University of Nottingham; Norfolk and Norwich University Hospitals NHS Foundation Trust; University of East Anglia; University Hospital Southampton NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Primary care; Antibiotic resistance; Antibiotic treatment; Cost consequences
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Connective Tissue Diseases; Skin Diseases, Infectious; Suppuration; Cellulitis; Anti-Infective Agents; Anti-Bacterial Agents; Floxacillin
• Other Study ID Numbers: ERGO 67073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Data from all centers will be analyzed together and published as soon as possible.

Planned publication of the results in a high-impact peer-reviewed journal. Planned publication of protocol in a peer-review journal. The datasets generated and/or analyzed during the current study will be published as a supplement to the publication of the results. Individual investigators may not publish data concerning their patients that are directly relevant to questions posed by the trial until the Trial Management Group (TMG) has published its report. The TMG will form the basis of the Writing Committee and advise on the nature of publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No