Clinical trial NCT01029782: Comparison of Intravenous Cefazolin Plus Oral Probenecid With Oral Cephalexin for the Treatment of Cellulitis
Official title: Intravenous Cefazolin Plus Oral Probenecid vs. Oral Cephalexin for the Treatment of Cellulitis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cellulitis
Keywords: Cellulitis
Emergency Department
Cefazolin
Probenecid
Cephalexin
Lead sponsor: Kelowna General Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Canadian Society of Hospital Pharmacists
name: Capital Health, Canada
name: Interior Health Authority, Canada
First posted: 2009-12-10
Enrollment: 206
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: The Number of Patients Failing Therapy After 72 Hours of Antibiotic Treatment With Oral Cephalexin or Intravenous Cefazolin Plus Oral Probenecid.
timeFrame: 72 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
Study officials:
affiliation: Interior Health
name: Dawn Dalen, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: Capital Health, Canada
name: Peter Zed, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dalen D, Fry A, Campbell SG, Eppler J, Zed PJ. Intravenous cefazolin plus oral probenecid versus oral cephalexin for the treatment of skin and soft tissue infections: a double-blind, non-inferiority, randomised controlled trial. Emerg Med J. 2018 Aug;35(8):492-498. doi: 10.1136/emermed-2017-207420. Epub 2018 Jun 18.