Duration of ANtibiotic Therapy for CEllulitis

Study Overview
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Brief Summary
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Cellulitis is among the most common infections leading to hospitalization, yet the optimal duration of therapy remains ill defined. Pragmatically, Dutch guidelines advise 10-14 days of antibiotics, which is the current standard of care. Recently it has been shown that antibiotic treatment for pneumonia and urinary tract infections can safely and significantly be shortened. Importantly, in an outpatient setting, treatment of uncomplicated cellulitis with 5 days of antibiotics was as effective as 10 days. We hypothesize that there is no difference in outcomes when patients hospitalized with cellulitis are treated with either a short-course (6 days) or standard-course (12 days) of antibiotics.

Official Title
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Duration of Antibiotic Therapy for Cellulitis (DANCE): a Randomized Controlled Trial Comparing 6 to 12 Days of Antibiotic Therapy for Patients Hospitalized With Cellulitis

Conditions
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Cellulitis, Erysipelas

Intervention / Treatment
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* Drug: Flucloxacillin
* Drug: Placebo (for flucloxacillin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to receive intravenous antibiotics for cellulitis/erysipelas 18 years of age or older Capable of giving written informed consent, able to comply with study requirements and restrictions Exclusion Criteria: Allergy for flucloxacillin, other beta-lactam antibiotics or one of the additives, or flucloxacillin induced hepatitis or liver enzyme disorders. Concurrent use of antibiotics for other indications Alternative diagnosis accounting for the clinical presentation. All cases involving any of the following complicating factors: Use of antibiotics with Gram-positive activity for more than 4 days in the past 7 days Intensive care unit admission during the last 7 days Severe peripheral arterial disease (Fontaine IV) Severe cellulitis necessitating surgical debridement or fascial biopsy Necrotizing fasciitis Periorbital or perirectal involvement Surgery Life expectancy less than one month Risk factors associated with Gram-negative pathogens as a causative agent: Chronic or macerated infra-malleolar ulcers, or infra-malleolar ulcers with previous antibiotic treatment, in patients with diabetes mellitus. Neutropenia Cirrhosis (Child-Pugh class B or C) Intravenous drug use Human or animal bite Skin laceration acquired in fresh or salt open water Fish fin or bone injuries

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard course<br>Flucloxacillin (1000mg iv OR, later, 500mg capsules), every 6 hours, for 6 days, followed by: Flucloxacillin 500mg capsules, every 6 hours, for 6 days | Drug: Flucloxacillin<br> <br> * Other names: Floxapen;|
| Experimental: Short course<br>Flucloxacillin (1000mg iv OR, later, 500mg capsules), every 6 hours, for 6 days, followed by: Placebo (for flucloxacillin 500mg) 500mg capsules, every 6 hours, for 6 days | Drug: Flucloxacillin<br> <br> * Other names: Floxapen;Drug: Placebo (for flucloxacillin)<br>* Sugar capsule manufactured to mimic flucloxacillin 500mg capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1/2: Resolution... | Resolution of cellulitis at day 14, defined as disappearance of warmth and tenderness at the site of infection, with substantial improvement in erythema and edema | day 14 | 
| Part 2/2: ...without relapse | No recurrence by day 28, defined as the need for additional antibiotic therapy for cellulitis | day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution without relapse | Other operators used to define resolution at day 14 (no fever; reduction in combined erythema/edema/warmth/tenderness score of at least 2 points, or reach 0) and relapse at day 28 (no fever; stable or further improved combined score; no new antibiotics for cellulitis) | day 28 | 
| Recurrence at day 90 | Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis | 90 days | 
| Objective speed of recovery | Improvement in cellulitis severity score (a 7 item scoring system, each with a score between 0-3; items are erythema, warmth, tenderness, edema, ulceration, drainage and fluctuance). Determined at day 1, day 2-3, day 5-6, day 14, and day 28 | Up to 90 days | 
| Health related Quality of Life | Using questionnaires Dutch SF-36 and EQ-5D at day 1, day 28, and day 90 | Up to 90 days | 
| Health care resource utilisation | Determined by total antibiotic use and effect on direct and indirect health-care associated costs, using modified versions of iMTA's Productivity Cost Questionnaire (iPCQ) and Medical Consumption Questionnaire (iMCQ). Measured at day 5-6, day 28 and day 90. | Up to 90 days | 
| Subjective speed of recovery | Visual Analog Scales (0-10) on pain and on swelling. Determined at day 1, day 2-3, day 5-6, day 14, day 28, and day 90 | Up to 90 days | 
| Additional antibiotic usage | Total usage of additional antibiotics for cellulitis between the end of treatment and day 90. | Up to 90 days | 
| Time to relapse | Time between end of treatment and the need for additional antibiotics for cellulitis | Up to 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotics, flucloxacillin, therapy duration, cellulitis, erysipelas, skin infections, hospital