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

Tracking Information

• First Submitted Date: June 10, 2013
• First Posted Date: June 12, 2013
• Last Update Posted Date: August 17, 2022
• Study Start Date: October 2013
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2014)

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

Original Primary Outcome Measures (submitted: June 11, 2013)

Improvement based on a composite of systemic and local features [ Time Frame: Day 5 ]

Temperature less than 37.5 degrees centigrade, and a reduction in limb swelling

Current Secondary Outcome Measures (submitted: June 11, 2013)

• Decrease in pain [ Time Frame: Day 10 ]
  Assessed using a visual analogue score
• 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.
• Physiological recovery [ Time Frame: Day 10 ]
  Resolution of systemic features, composite inflammatory markers and recovery of renal function.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adjunctive Clindamycin for Cellulitis: C4C Trial.
• 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
• 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.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cellulitis

Intervention

• 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
• Drug: Placebo oral capsule
  Placebo is externally identical to the over-encapsulated clindamycin and is taken four times each day for 2 days

Study Arms

• Placebo Comparator: Flucloxacillin and Placebo oral capsule
  Intravenous or oral Flucloxacillin with a Placebo oral capsule
  Interventions:

  • Drug: Flucloxacillin
  • Drug: Placebo oral capsule
• Active Comparator: Flucloxacillin and Clindamycin
  Intravenous or oral Flucloxacillin with Clindamycin oral capsule
  Interventions:

  • Drug: Flucloxacillin
  • Drug: Clindamycin

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 16, 2022): 410
• Original Estimated Enrollment (submitted: June 11, 2013): 450
• Actual Study Completion Date: March 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01876628
• Other Study ID Numbers: C4C-4078; 2013-001218-14 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: University Hospitals Bristol and Weston NHS Foundation Trust
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
• Original Study Sponsor: Same as current

Collaborators

• University of Bristol
• Public Health England

• Investigators: Not Provided
• PRS Account: University Hospitals Bristol and Weston NHS Foundation Trust
• Verification Date: August 2022