RCT to Investigate if Prophylactic Antibiotics Prevent Further Episodes of Cellulitis (Erysipelas) of the Leg (PATCH1)

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 Overview

• Status: Completed
• Conditions: Cellulitis/Erysipelas of the Leg
• Intervention / Treatment: Drug: Penicillin VK; Other: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ireland
  • Cork, Ireland
    • South Infirmary-Victoria University Hospital
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • Amersham, United Kingdom, HP7 0JD
    • Amersham Hospital
  • Brighton, United Kingdom, BN2 3EW
    • Brighton General Hospital
  • Bristol, United Kingdom, BS2 8HW
    • Bristol Royal Infirmary
  • Carlisle, United Kingdom, CA2 7HY
    • Cumberland Infirmary
  • Derby, United Kingdom, DE1 2QY
    • Derbyshire Royal Infirmary
  • Durham, United Kingdom, DE1 5TW
    • University Hospital of North Durham
  • Gloucester, United Kingdom, GL1 3NN
    • Gloucestershire Royal Infirmary
  • Great Yarmouth, United Kingdom, NR31 6LA
    • James Paget University Hospital
  • Hull, United Kingdom, HU8 9HE
    • Princess Royal Hospital
  • Ipswich, United Kingdom, IP4 5HD
    • Ipswich Hospital
  • King's Lynn, United Kingdom, PE30 4ET
    • Queen Elizabeth Hospital
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Liverpool, United Kingdom, L14 3LB
    • Broadgreen Hospital
  • Londonderry, United Kingdom, BT47 6SB
    • Altnagelvin Area Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospital
  • Reading, United Kingdom, RG1 5AN
    • Royal Berkshire Hospital
  • Salford, United Kingdom, M6 8HD
    • Hope Hospital
  • Sutton in Ashfield, United Kingdom, NG17 4JL
    • King's Mill Hospital
  • Swansea, United Kingdom, SA2 8QA
    • Singleton Hospital
  • Watford, United Kingdom, WD1 8HB
    • Watford General Hospital
  • York, United Kingdom, YO31 8HR
    • York Hospital
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Queens Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Penicillin VK 250 mg b.d.	Drug: Penicillin VK; Biconcave tablet 250mg oral, b.d.
Placebo Comparator: 2; placebo tablet b.d.	Other: placebo; biconcave tablet matching active comparator as much as possible in size and shape

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is time to next episode of cellulitis	variable

Secondary Outcome Measures

Outcome Measure	Time Frame
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).	variable

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: UK Dermatology Clinical Trials Network; Action Medical Research
• Investigators: Study Director: Hywel Williams, Professor, University of Nottingham

Publications and helpful links

Helpful Links

• study website

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: November 1, 2007
• First Submitted That Met QC Criteria: November 1, 2007
• First Posted (Estimate): November 2, 2007

Study Record Updates

• Last Update Posted (Estimate): July 24, 2012
• Last Update Submitted That Met QC Criteria: July 23, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: clinical trial; penicillin; lymphoedema; cellulitis
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Inflammation; Connective Tissue Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Skin Diseases, Infectious; Suppuration; Skin Diseases, Bacterial; Cellulitis; Erysipelas; Anti-Infective Agents; Anti-Bacterial Agents; Penicillins; Penicillin V
• Other Study ID Numbers: 06002; ISRCTN34716921; EudraCT No. 2006-000381-36