Randomized Trial to Assess PO Versus IV Antibiotics

NCT01714596 | Completed DMC

• 1 other identifier: METRC POvIV
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 24

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.

Conditions

Wound Infection

Keywords

Oral Antibiotic; Intravenous Antibiotic; Wound infection; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Study injury related surgical interventions by 1 year

  1 year

Secondary Outcomes (5)

• Treatment Failure by 1 year

  1 year

• Re-hospitalizations by 1 year

  1 year

• Healthcare costs

  1 year

• Medication Adherence

  1 year

• Satisfaction with treatment

  1 year

Study Arms (2)

Oral Antibiotic

ACTIVE COMPARATOR

Oral Antibiotic Arm; Participants assigned to this group will receive oral antibiotics as prescribed by their treating physician.

Other: PO versus IV antibiotics Route of administration evaluation

IV Antibiotic

ACTIVE COMPARATOR

Participants assigned to this group will receive intravenous (IV) antibiotics as prescribed by their treating physician.

Other: PO versus IV antibiotics Route of administration evaluation

Interventions

PO versus IV antibiotics Route of administration evaluation OTHER

This is a study of oral (per os, (PO)) antibiotic therapy versus intravenous (IV) antibiotics in the treatment of acute infection after fixation of fractures and joint fusions. This is not a study of an experimental drug but a study of route of administration of standard use antibiotics. Antibiotic regimen options decision will be made by the Study Surgeon at each site in consult with local Infectious Disease experts based on local standard practices and bacterial susceptibilities.

Also known as: based on local practices and bacterial susceptibilities

IV Antibiotic; Oral Antibiotic

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• Patients diagnosed with a wound infection of the study injury, defined as patients with at least one of the following:
• Deep culture positive after operative debridement.
• Cultures positive in thio only after operative debridement.
• Negative culture after operative debridement if wound infection meets the Center for Disease control and Prevention (CDC) criteria.
• Patients who are English or Spanish competent.
• Patients aged 18 - 84.
• Patients with bacteria susceptible to both PO and IV antibiotics.
• Patients able to be treated for their infection at the METRC facility for at least 12 months following definitive surgical procedure
• Patients may have multiple eligible study-eligible injuries.
• Patients may have temporary external fixation prior to definitive fixation.
• Patients may have received antibiotics prior to operative wound debridement.
• Patient is able to obtain study medication(s).
• Patient may be pregnant at the time of screening.

You may not qualify if:

• Patients who have high risk of amputation of the study limb (based on opinion of the initial managing physician).
• Patients undergoing treatment with any other investigational therapy within the month preceding implantation or planned within the 12 months following implantation.
• 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.
• Patients with pathological fractures; a known history of Paget's disease.
• Patients for whom the definitive treatment of the study injury was an external fixator.
• Patients who are currently on Selective Serotonin Reuptake Inhibitor (SSRI) medication (e.g. Zoloft, Prozac, Celexa), and bacteria is MRSA
• Patients with cultures positive in thio only.
• 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. .
• Patients or designated proxy who are unwilling to provide consent.
• Patients with a history of IV drug use who in the investigator's opinion are unsuitable candidates for IV therapy.
• 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.
• Patients with traumatic brain injury or who are intellectually challenged and who lack adequate family support to ensure adherence to the protocol.
• Patients unable to swallow oral medications or without adequately functioning GI tract.
• 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).

Sponsors & Collaborators

• Major Extremity Trauma Research Consortium: lead

Study Sites (24)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, United States

Location

University of California at San Francisco

San Francisco, California, United States

Location

Denver Health and Hospital Authority

Denver, Colorado, United States

Location

University of Miami Ryder Trauma Center

Miami, Florida, United States

Location

Eskenazi Health

Indianapolis, Indiana, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Location

University of Maryland R Adams Cowley Shock Trauma Center

Baltimore, Maryland, United States

Location

Boston Medical Center

Boston, Massachusetts, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Location

St. Louis University Medical Center

St Louis, Missouri, United States

Location

Jamaica Hospital Medical Center

Jamaica, New York, United States

Location

NYU Langone Medical Center

New York, New York, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, United States

Location

Penn State University M.S. Hershey Medical Center

Hershey, Pennsylvania, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

San Antonio Military Medical Center (SAMMC)

San Antonio, Texas, United States

Location

University of Virginia

Charlottesville, Virginia, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, United States

Location

Naval Medical Center Portsmouth

Portsmouth, Virginia, United States

Location

University of Washington/Harborview Medical Center

Seattle, Washington, United States

Location

University of Wisconsin

Madison, Wisconsin, United States

Location

Related Publications (1)

• Major Extremity Trauma Research Consortium (METRC); Obremskey WT, O'Toole RV, Morshed S, Tornetta P 3rd, Murray CK, Jones CB, Scharfstein DO, Taylor TJ, Carlini AR, DeSanto JM, Castillo RC, Bosse MJ, Karunakar MA, Seymour RB, Sims SH, Weinrib DA, Churchill C, Carroll EA, Pilson HT, Goodman JB, Holden MB, Miller AN, Sietsema DL, Stahel PF, Mir H, Schmidt AH, Westberg JR, Mullis B, Shively KD, Hymes RA, Konda SR, Vallier HA, Breslin MA, Smith CS, Crickard CV, Reid JS, Baker M, Eglseder WA, LeBrun C, Manson T, Mascarenhas DC, Nascone J, Pollak AN, Schloss MG, Sciadini MF, Degani Y, Miclau T, Weiss DB, Yarboro SR, McVey ED, Firoozabadi R, Agel J, Burgos EJ, Gajari V, Rodriguez-Buitrago A, Tummuru RR, Trochez KM. Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial. JAMA Surg. 2025 Mar 1;160(3):276-284. doi: 10.1001/jamasurg.2024.6439.

  PMID: 39841468 DERIVED

MeSH Terms

Conditions

Wound Infection

Condition Hierarchy (Ancestors)

Infections

Study Officials

• William T Obremskey, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Renan Castillo, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Tara Taylor, MPH

  Johns Hopkins Bloomberg School of Public Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: October 26, 2012
• Study Start: December 3, 2013
• Primary Completion: September 30, 2019
• Study Completion: December 30, 2020
• Last Updated: February 11, 2021

Record last verified: 2021-02

Locations

US (24)