Randomized Trial to Assess PO Versus IV Antibiotics

Not Applicable

Completed

• Conditions: Wound Infection
• Interventions: Other: PO versus IV antibiotics Route of administration evaluation

• Registration Number: NCT01714596
• Lead Sponsor: Major Extremity Trauma Research Consortium

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-04-30
• Study First Submitted QC: 2012-10-25
• Study First Posted: 2012-10-26
• Study Start: 2013-12-03
• Primary Completion: 2019-09-30
• Study Completion: 2020-12-30
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-08
• Last Update Posted: 2021-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 233

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV Antibiotic	PO versus IV antibiotics Route of administration evaluation	Participants assigned to this group will receive intravenous (IV) antibiotics as prescribed by their treating physician.
Oral Antibiotic	PO versus IV antibiotics Route of administration evaluation	Oral Antibiotic Arm; Participants assigned to this group will receive oral antibiotics as prescribed by their treating physician.

Primary Outcome Measures

Name	Time	Method
Study injury related surgical interventions by 1 year	1 year

Secondary Outcome Measures

Name	Time	Method
Healthcare costs	1 year	Cost of PO versus IV medications include medical record and bill abstracted costs associated with outpatient clinic visits, home health visits, medication, subsequent hospital readmission, and other types of medical care as identified over the course of the study.
Satisfaction with treatment	1 year	Patient satisfaction with treatment measured by Short Form Patient Satisfaction Questionnaire (PSQ-18); The PSQ-18 measures 6 domains: technical quality, interpersonal manner, communication, financial aspects of care, time spent with doctor, and accessibility. A score of 0.8 or higher in each domain correlates with improved satisfaction.
Treatment Failure by 1 year	1 year	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.
Re-hospitalizations by 1 year	1 year	Re-hospitalization for complications, such as infection, non-union and amputation
Medication Adherence	1 year	Patient adherence to PO and IV medications; Patient adherence with PO antibiotics will be monitored through wireless-enabled microchip monitors embedded in pill bottles by the Medication Event Monitoring System (MEMS) and weekly adherence questionnaire.

Trial Locations

Locations (24)

St. Louis University Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Carolinas Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Wake Forest Baptist Medical Center; 🇺🇸 Winston-Salem, North Carolina, United States

Penn State University M.S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Naval Medical Center Portsmouth; 🇺🇸 Portsmouth, Virginia, United States

University of Maryland R Adams Cowley Shock Trauma Center; 🇺🇸 Baltimore, Maryland, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Iowa Hospitals & Clinics; 🇺🇸 Iowa City, Iowa, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of Washington/Harborview Medical Center; 🇺🇸 Seattle, Washington, United States

Jamaica Hospital Medical Center; 🇺🇸 Jamaica, New York, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

Denver Health and Hospital Authority; 🇺🇸 Denver, Colorado, United States

University of Miami Ryder Trauma Center; 🇺🇸 Miami, Florida, United States

Eskenazi Health; 🇺🇸 Indianapolis, Indiana, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

San Antonio Military Medical Center (SAMMC); 🇺🇸 San Antonio, Texas, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States