Official Title: “Randomised Controlled Trial to Investigate Whether Prophylactic Antibiotics Can Prevent Further Episodes of Cellulitis (Erysipelas) of the Leg (PATCH I)”

To assess whether a period of prophylactic penicillin after an episode of cellulitis of the leg reduces the risk of repeat episodes. Participants are randomised to receive 12 months of prophylaxis (penicillin VK 250mg b.d. or placebo). The PATCH I study will recruit only patients with recurrent disease.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: May 2009

Cellulitis of the leg is an common, acute, painful and potentially serious infection of the skin and subcutaneous tissue. It currently accounts for 2-3% of UK hospital admissions. The average length of in-patient stay is 9 days (Hospital Episode Statistics, Department of Health (UK), 2002-2003) and 25-50% of treated patients suffer further episodes and other morbidity, such as oedema and ulceration.

Cellulitis of the lower leg is usually due to streptococcal infection that has entered into the body via a relatively subtle portal, such as toeweb fissures. Penicillin is the most useful of the commonly used oral antibiotics against streptococci, although other agents such as flucloxacillin are often used if staphylococcal infection is a clinical possibility.

There are numerous risk factors for cellulitis of the lower leg and recurrent disease is one the biggest problems.

Existing evidence for the use of prophylactic antibiotics to prevent further episodes is very limited. Two small randomised controlled trials (RCTs) hint at possible benefit, but these studies are very small (16 and 40 participants respectively). Despite this, many physicians routinely use prophylactic antibiotics for recurrent cellulitis, although opinions on the value of such practice is firmly divided.

This study will recruit over a 12-24 month period participants who have completed the therapy for the current episode of cellulitis. Participants will be followed up for up to 24 months with telephone calls at 10 days, 3 months, 6 months, 9 months and 12 months and then every 6 months after completing the intervention. A diary will also be provided as an "aid memoir" to phone calls and to note missed tablets and recurrence of cellulitis.

Intervention(s) in this Clinical Trial

• Drug: Penicillin VK
  • Biconcave tablet 250mg oral, b.d.
• Other: placebo
  • biconcave tablet matching active comparator as much as possible in size and shape

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Penicillin VK 250 mg b.d.
• Placebo Comparator: 2
  • placebo tablet b.d.

Primary Measures

• The primary outcome is time to next episode of cellulitis
  • Time Frame: variable
    Safety Issue?: No

Secondary Measures

• Secondary outcomes include: i) the proportion of participants with repeat episodes of cellulitis; ii) proportion of participants with oedema and/or ulceration; iii) cost-effectiveness; iv) predictors of response (multiple regression model).
  • Time Frame: variable
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of cellulitis of either leg AND a history of at least one previous episode of cellulitis of either leg within the three

Exclusion Criteria:

• Any doubt about the certainty of the diagnosis of either the index episode or the previous episode (if applicable), will be grounds for exclusion. Additionally, patients with any of the following will be excluded:
• Taken antibiotic prophylaxis (defined as more than 3 months usage) for the prevention of cellulitis within 6 months prior to index episode.
• A time lapse of longer than 12 weeks since the start of treatment for the index episode to the date of potential randomisation into the trial.
• Known allergy to penicillin.
• Preceding leg ulceration, surgery or penetrating trauma, as these cases are more likely to be caused by staphylococcal infection. (NB: this does not exclude patients with toeweb maceration/tinea pedis or other minor/blunt wounds).
• Treating physician or principal investigator unwilling to randomise patient. This includes, but is not limited to:
• The treating physician and/or patient feels that prophylactic antibiotics are not in the patient's best interests and therefore entry to this study would be inappropriate.
• The treating physician and/or patient feels it would not be ethical or appropriate for the patient to receive placebo and so they are not willing/able to accept randomisation
• Concomitant medication that would mean that long-term penicillin is
inappropriate
• Diagnostic uncertainty
• Gastrointestinal disease causing persistent diarrhoea or vomiting severe enough to affect the absorption of the phenoxymethylpenicillin.
• Allergic diathesis or severe bronchial asthma severe enough to preclude the use of phenoxymethylpenicillin.
• Confounding concurrent disease (e.g. DVT).
• No access to a telephone.
• Aged less than 16 years.
• Unable to give informed consent.
• Already taking part in a research study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Nottingham

Overall Clinical Trial Officials and Contacts

Hywel Williams, Professor Study Director University of Nottingham  

Overall Contact: Katharine Foster, PhD 0115 8468626 patch@nottingham.ac.uk

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00552799

Study ID Number: 26083

ClinicalTrials.gov Identifier: NCT00552799

Health Authority: United Kingdom: Research Ethics Committee

study website