Clinical trial NCT01714596: Randomized Trial to Assess PO Versus IV Antibiotics
Official title: A Prospective Randomized Trial to Assess PO Versus IV Antibiotics for the Treatment of Post-op Wound Infection After Extremity Fractures (POvIV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Wound Infection
Keywords: Oral Antibiotic
Intravenous Antibiotic
Wound infection
Randomized Controlled Trial
Lead sponsor: Major Extremity Trauma Research Consortium
Sponsor class: OTHER
First posted: 2012-10-26
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to evaluate the effect of treatment of post-op wound infection in long bones after fracture fixation or joint fusion and either: (Group 1) operative debridement and PO antibiotic treatment for 6 weeks; or (Group 2) operative debridement and IV antibiotics for 6 weeks.

Primary Hypothesis 1: The rate of study injury related surgical interventions by one year in Group 1 will be non-inferior to the rate in Group 2.

Secondary Hypothesis 1: The rate of treatment failure by one year in Group 1 will be non-inferior to the rate in Group 2. Treatment failure is defined as wound problems that require surgery \>2 weeks after initial debridement, infection recurrence, infection with a new pathogen, joint erosion, implant failure, medical problems related to the treatment administration which necessitates a switch from one arm to the other.

Secondary Hypothesis 2: The rate of re-hospitalization for complications, infection, non-union and amputation by one year in Group 1 will be non-inferior to the rate in Group 2.

Secondary Hypothesis 3: Following discharge for treatment of infection, per patient treatment costs at 1 year will be lower in Group 1 than in Group 2.

Secondary Hypothesis 4: Adherence in Group 1 will be non-inferior to adherence in Group 2.

Secondary Hypothesis 5: Patient satisfaction with treatment in Group 1 will be non-inferior to adherence in Group 2.

Specific Aim 2: To build and validate a risk prediction model for failure of treatment of early post-op wound infections after fixation of fractures and joint fusions.


Eligibility criteria: Inclusion Criteria:

1. Patients with any fractures of any bone at or proximal to and including the tarsal/metatarsal joint (Lisfranc) or proximal to the carpal joints (includes distal radius fractures), excluding the spine, treated with any type of internal fixation, or
2. Patients undergoing fusion of any bone at or proximal to and including the subtalar joint or radial carpal joint, (excluding the spine) that develop a post op wound infection at any time.
3. Patients diagnosed with a wound infection of the study injury, defined as patients with at least one of the following:

   1. Deep culture positive after operative debridement.
   2. Cultures positive in thio only after operative debridement.
   3. Negative culture after operative debridement if wound infection meets the Center for Disease control and Prevention (CDC) criteria.
4. Patients who are English or Spanish competent.
5. Patients aged 18 - 84.
6. Patients with bacteria susceptible to both PO and IV antibiotics.
7. Patients able to be treated for their infection at the METRC facility for at least 12 months following definitive surgical procedure
8. Patients may have multiple eligible study-eligible injuries.
9. Patients may have temporary external fixation prior to definitive fixation.
10. Patients may have received antibiotics prior to operative wound debridement.
11. Patient is able to obtain study medication(s).
12. Patient may be pregnant at the time of screening.

Exclusion Criteria:

1. Patients who have high risk of amputation of the study limb (based on opinion of the initial managing physician).
2. Patients undergoing treatment with any other investigational therapy within the month preceding implantation or planned within the 12 months following implantation.
3. Patients with history of chronic infection at the site of study injury, defined as:

   patients with chronic osteomyelitis identified by radiographic erosion or sequestrum; or patients with more than one instance of surgical treatment of infection and approximately 6 week course of antibiotics.
4. Patients with pathological fractures; a known history of Paget's disease.
5. Patients for whom the definitive treatment of the study injury was an external fixator.
6. Patients who are currently on Selective Serotonin Reuptake Inhibitor (SSRI) medication (e.g. Zoloft, Prozac, Celexa), and bacteria is MRSA
7. Patients with cultures positive in thio only.
8. Patients who are incarcerated or who have unstable housing situations due to concerns regarding ability to receive home care, adherence phone calls, and maintain follow up. .
9. Patients or designated proxy who are unwilling to provide consent.
10. Patients with a history of IV drug use who in the investigator's opinion are unsuitable candidates for IV therapy.
11. Patients likely to have severe problems maintaining follow-up, including patients diagnosed with a severe psychiatric conditions, patients who live too far outside the hospital's catchment area.
12. Patients with traumatic brain injury or who are intellectually challenged and who lack adequate family support to ensure adherence to the protocol.
13. Patients unable to swallow oral medications or without adequately functioning GI tract.
14. Patients who, based upon the clinical judgment of the treating clinician, are NOT equally suited for treatment with either oral or intravenous antibiotics (i.e., those for whom there is a clinical treatment preference).

Primary outcomes:
measure: Study injury related surgical interventions by 1 year
timeFrame: 1 year
Secondary outcomes:
measure: Treatment Failure by 1 year
timeFrame: 1 year
measure: Re-hospitalizations by 1 year
timeFrame: 1 year
measure: Healthcare costs
timeFrame: 1 year
measure: Medication Adherence
timeFrame: 1 year
measure: Satisfaction with treatment
timeFrame: 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Miami
country: United States
facility: University of Miami Ryder Trauma Center
state: Florida
city: Indianapolis
country: United States
facility: Eskenazi Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland R Adams Cowley Shock Trauma Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis University Medical Center
state: Missouri
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State University M.S. Hershey Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: San Antonio Military Medical Center (SAMMC)
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center Portsmouth
state: Virginia
city: Seattle
country: United States
facility: University of Washington/Harborview Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Vanderbilt University Medical Center
name: William T Obremskey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Renan Castillo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Tara Taylor, MPH
role: STUDY_DIRECTOR
References: