Comparison of Intravenous Cefazolin Plus Oral Probenecid With Oral Cephalexin for the Treatment of Cellulitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Kelowna General Hospital
Sponsor:
Collaborators:
Canadian Society of Hospital Pharmacists
Capital Health, Canada
Interior Health Authority, Canada
Information provided by (Responsible Party):
Dawn Dalen, Kelowna General Hospital
ClinicalTrials.gov Identifier:
NCT01029782
First received: December 9, 2009
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine whether oral cephalexin is equivalent to intravenous cefazolin plus oral probenecid for the treatment of uncomplicated skin and soft tissue infections in patients that present to the emergency department.


Condition Intervention Phase
Cellulitis
Drug: IV cefazolin plus oral probenecid and placebo cephalexin
Drug: Oral cephalexin and saline IV plus probenecid placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intravenous Cefazolin Plus Oral Probenecid vs. Oral Cephalexin for the Treatment of Cellulitis: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Kelowna General Hospital:

Primary Outcome Measures:
  • The proportion of patients failing therapy after 72 hours of antibiotic treatment with oral cephalexin or intravenous cefazolin plus oral probenecid. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 320
Study Start Date: May 2010
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IV cefazolin plus oral probenecid and placebo cephalexin Drug: IV cefazolin plus oral probenecid and placebo cephalexin
Intravenous cefazolin 2 g IV plus probenecid 1 g daily plus cephalexin placebo orally four times daily.
Active Comparator: Oral cephalexin and saline IV plus probenecid placebo Drug: Oral cephalexin and saline IV plus probenecid placebo
Cephalexin 500 mg orally four times daily plus saline IV and oral probenecid placebo daily

Detailed Description:

Skin and soft tissue infections (SSTIs) are a common reason for presentation to an Emergency Department (ED) in Canada. Although many patients with mild SSTI are able to be managed at home with oral antibiotics, those with mild-moderate infections are often treated with parenteral antibiotics. Current practice patterns in Canadian EDs indicate this patient population is often treated with intravenous cefazolin once daily along with oral probenecid and return to the ED or other ambulatory setting for daily medication administration and assessment. This parenteral regimen has been found to result in success rates comparable to studies which have evaluated treatment success with oral antibiotics in this patient population (89-97%). Although successful outcome can be achieved with this approach, it is often inconvenient for the patient to return to the ED/ambulatory care unit daily and does contribute to overall ED/ambulatory care visit volumes and overall health care costs. Unfortunately, there has never been a study which has evaluated the relative efficacy and safety or oral antibiotics to the aforementioned parenteral approach in this patient population and thus there remains a significant knowledge gap which must be addressed before a change in current practice can be explored.

The objective of the study is to determine whether oral cephalexin is equivalent to intravenous cefazolin plus oral probenecid for the treatment of uncomplicated SSTIs in patients that present to the ED. This study will be a prospective, multi-centered, randomized controlled non-inferiority trial comparing cephalexin 500 mg orally four times to cefazolin 2 g IV plus probenecid 1 g orally, in patients presenting to the ED with presumed diagnosis of SSTI. The primary outcome will be to compare the proportion of patients failing therapy for their cellulitis after 72 hours of antibiotic treatment with oral cephalexin or IV cefazolin/oral probenecid 1 g daily. Secondary outcomes include the clinical cure rate at 7 days, percentage of patients requiring hospital admission, percentage of patients stepped down to oral antibiotics on or before day 7 of therapy, percentage of patients requiring an additional antibiotic prescription on day 7, and the frequency of adverse events.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients presenting to the emergency department with a presumed diagnosis of mild to moderate skin and soft tissue infection
  • Deemed well enough to be treated as an outpatient
  • 19 years of age or older

Exclusion Criteria:

  • known allergy to study drugs
  • known chronic kidney disease with a creatinine clearance <30 mL/min
  • known previous methicillin-resistant staphylococcus aureus (MRSA) infection
  • use of antibiotics for greater than 24 hours in the past 7 days
  • wound/abscess requiring operative debridement or incision and drainage
  • suspected necrotizing fasciitis, osteomyelitis or septic arthritis
  • febrile neutropenia
  • concomitant documented bacteremia
  • Two or more signs of systemic sepsis
  • new altered mental status
  • infections at a site involving prosthetic materials
  • animal or human bite wound infections
  • post-operative wound infections
  • known peripheral vascular disease
  • superficial thrombophlebitis
  • pregnant/breastfeeding
  • obesity (BMI > 30 kg/m2)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01029782

Locations
Canada, British Columbia
Kelowna General Hospital Recruiting
Kelowna, British Columbia, Canada, V1Y 1T2
Contact: Dawn Dalen, BSP, ACPR, PharmD    (250) 862-4300 ext 7446    dawn.dalen@interiorhealth.ca   
Principal Investigator: Dawn Dalen, BSP, ACPR, PharmD         
Sub-Investigator: Denise Sprague, BSc. (Pharm), ACPR, PharmD         
Sub-Investigator: Jeffrey Eppler, MD, FRCP(C)         
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: Peter Zed, BSc, BSc (Pharm), ACPR, PharmD    (902) 473-2967    peter.zed@cdha.nshealth.ca   
Principal Investigator: Peter Zed, BSc, BSc (Pharm), ACPR, PharmD         
Sub-Investigator: Samuel Campbell, MB BCh, CCFP(EM), Dip PEC (SA)         
Sponsors and Collaborators
Kelowna General Hospital
Canadian Society of Hospital Pharmacists
Capital Health, Canada
Interior Health Authority, Canada
Investigators
Principal Investigator: Dawn Dalen, PharmD Interior Health, Canada
Principal Investigator: Peter Zed, PharmD Capital Health, Canada
  More Information

No publications provided

Responsible Party: Dawn Dalen, Clinical Pharmacy Specialist, Emergency Medicine, Kelowna General Hospital
ClinicalTrials.gov Identifier: NCT01029782     History of Changes
Other Study ID Numbers: KGHQEII-0001
Study First Received: December 9, 2009
Last Updated: May 29, 2014
Health Authority: Canada: Health Canada

Keywords provided by Kelowna General Hospital:
Cellulitis
Emergency Department
Cefazolin
Probenecid
Cephalexin

Additional relevant MeSH terms:
Cellulitis
Skin Diseases, Infectious
Infection
Suppuration
Connective Tissue Diseases
Inflammation
Pathologic Processes
Cefazolin
Cephalexin
Probenecid
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Uricosuric Agents
Gout Suppressants
Antirheumatic Agents
Renal Agents

ClinicalTrials.gov processed this record on July 31, 2014