Adjunctive Clindamycin for Cellulitis: C4C Trial. (C4C)

A Double Blind Randomised Control Trial to Measure the Effect of the Addition of Clindamycin to Flucloxacillin for the Treatment of Limb Cellulitis

The aim of this study is to see whether the addition of Clindamycin, a protein inhibiting antibiotic, to the standard antibiotic treatment of limb cellulitis, with Flucloxacillin, results in less tissue damage and a more rapid resolution of both systemic and local features, in a cost-effective manner. This study is a randomised controlled trial comparing Clindamycin with placebo.

Study Overview

• Status: Completed
• Conditions: Cellulitis
• Intervention / Treatment: Drug: Flucloxacillin; Drug: Placebo oral capsule; Drug: Clindamycin

Detailed Description

Criteria to be used to assess tissue damage and clinical response:

1. Fever, tachycardia, neutrophil count, urea and other laboratory parameters at five and ten days post first dose of clindamycin
2. Limb swelling (by the measurement of limb circumference), skin surface temperature and tissue damage (by the proportion of the limb affected)
3. Document the duration between initial systemic features and the development of local signs
4. Examine the effect of the duration between systemic and local features and first dose of flucloxacillin on the subsequent duration and severity of cellulitis
5. Examine the effect of duration between the first dose of flucloxacillin and the first dose of clindamycin on the subsequent duration and severity of cellulitis
6. Identify and quantify possible side effects of clindamycin

• Study Type: Interventional
• Enrollment (Actual): 410
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS2 8HW
    • University Hospitals Bristol NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female subjects aged 18 or over who have a diagnosis of cellulitis of a single, upper or lower, limb
• Who are able to understand the study and give consent
• Who are able to take oral medication

Exclusion Criteria:

• Patients with a confirmed history of penicillin, flucloxacillin or clindamycin allergy
• Patients known to be colonised with Methicillin-resistant Staphylococcus aureus or Methicillin-resistant Staphylococcus aureus isolated from wound within the last year
• Patients unable to take oral medication
• Previous history of Clostridium difficile colitis
• Clindamycin taken within the last 30 days
• Clinically unstable
• Unable to understand the study or give consent
• Any doubt over the certainty of the diagnosis of cellulitis
• Patients taking any drug that is incompatible with either flucloxacillin or clindamycin
• Pre-existing diarrhoea

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: Flucloxacillin and Placebo oral capsule; Intravenous or oral Flucloxacillin with a Placebo oral capsule	Drug: Flucloxacillin; Intravenous or oral Flucloxacillin. Minimum dose 500mg four times each day. Target duration 5 days less pre-recruitment beta-lactam duration.; Other Names: Floxapen; Fluclomix; Ladropen; Drug: Placebo oral capsule; Placebo is externally identical to the over-encapsulated clindamycin and is taken four times each day for 2 days
Active Comparator: Flucloxacillin and Clindamycin; Intravenous or oral Flucloxacillin with Clindamycin oral capsule	Drug: Flucloxacillin; Intravenous or oral Flucloxacillin. Minimum dose 500mg four times each day. Target duration 5 days less pre-recruitment beta-lactam duration.; Other Names: Floxapen; Fluclomix; Ladropen; Drug: Clindamycin; Clindamycin dose 300mg four times each day for 2 days, within 48 hours of commencing flucloxacillin. Clindamycin is over-encapsulated and externally identical to placebo.; Other Names: Cleocin; Dalacin C; Daclin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement based on a composite of systemic and local features	Temperature less than 37.5 degrees centigrade, reduction in limb swelling and reduction in skin temperature	Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in pain	Assessed using a visual analogue score	Day 10
Quality of life	Assessment based on a questionnaire plus return to work or normal activities and absence of increased side-effects.	Day 30
Physiological recovery	Resolution of systemic features, composite inflammatory markers and recovery of renal function.	Day 10

Collaborators and Investigators

• Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
• Collaborators: Public Health England; University of Bristol

Publications and helpful links

General Publications

• Brindle R, Williams OM, Davies P, Harris T, Jarman H, Hay AD, Featherstone P. Adjunctive clindamycin for cellulitis: a clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis. BMJ Open. 2017 Mar 17;7(3):e013260. doi: 10.1136/bmjopen-2016-013260.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 10, 2013
• First Submitted That Met QC Criteria: June 11, 2013
• First Posted (Estimate): June 12, 2013

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; Cellulitis; Clindamycin; Flucloxacillin; Group A streptococcus
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Connective Tissue Diseases; Skin Diseases, Infectious; Suppuration; Cellulitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Floxacillin
• Other Study ID Numbers: C4C-4078; 2013-001218-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes