Adjunctive Clindamycin for Cellulitis: C4C Trial. (C4C)

• ClinicalTrials.gov Identifier: NCT01876628
• Recruitment Status: Completed
• First Posted: June 12, 2013
• Last Update Posted: August 17, 2022
• Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
• Collaborators: University of Bristol; Public Health England
• Information provided by (Responsible Party): University Hospitals Bristol and Weston NHS Foundation Trust

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cellulitis	Drug: Flucloxacillin; Drug: Clindamycin; Drug: Placebo oral capsule	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 410 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind Randomised Control Trial to Measure the Effect of the Addition of Clindamycin to Flucloxacillin for the Treatment of Limb Cellulitis
• Study Start Date: October 2013
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: March 2016

Arms and Interventions

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: Dalacin C; Daclin; Cleocin

Outcome Measures

Primary Outcome Measures :

1. Improvement based on a composite of systemic and local features [ Time Frame: Day 5 ]
   Temperature less than 37.5 degrees centigrade, reduction in limb swelling and reduction in skin temperature

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United Kingdom

University Hospitals Bristol NHS Foundation Trust

Bristol, United Kingdom, BS2 8HW

Sponsors and Collaborators

University Hospitals Bristol and Weston NHS Foundation Trust

University of Bristol

Public Health England

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospitals Bristol and Weston NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT01876628
• Other Study ID Numbers: C4C-4078; 2013-001218-14 ( EudraCT Number )
• First Posted: June 12, 2013
• Last Update Posted: August 17, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by University Hospitals Bristol and Weston NHS Foundation Trust:

Clindamycin; Cellulitis; Flucloxacillin; Group A streptococcus; Staphylococcus aureus

Additional relevant MeSH terms:

Cellulitis; Skin Diseases, Infectious; Infections; Suppuration; Connective Tissue Diseases; Inflammation; Pathologic Processes; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Floxacillin; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action