PO vs IV Antibiotics for the Treatment of Infected Nonunion of Fractures After Fixation

NCT05699174 | Recruiting Phase 3 DMC

• 1 other identifier: W81XWH2210635
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 13

Brief Summary

This is a Phase III clinical randomized control trial to investigate differences between patient with an infected nonunion treated by PO vs. IV antibiotics. The study population will be 250 patients, 18 years or older, being treated for infected nonunion after internal fixation of a fracture with a segmental defect less than one centimeter. Patients will be randomly assigned to either the treatment (group 1) PO antibiotics for 6 weeks or the control group (group 2) IV antibiotics for 6 weeks. The primary hypothesis is that the effectiveness of oral antibiotic therapy is equivalent to traditional intravenous antibiotic therapy for the treatment of infected nonunion after fracture internal fixation, when such therapy is combined with appropriate surgical management. Clinical effectiveness will be measured as the primary outcome as the number of secondary re-admissions related to injury and secondary outcomes of treatment failure (re-infection, nonunion, antibiotic complications) within the first one year of follow-up, as defined by specified criteria and determined by a blinded data assessment panel. In addition, treatment compliance, the cost of treatment, the number of surgeries required, the type and incidence of complications, and the duration of hospitalization will be measured.

Conditions

Infections; Infected Wound; Nonunion of Fracture; Injury Leg; Amputation; Fracture; Lower Extremity Fracture; Antibiotic Side Effect; Internal Fixation; Complications, Infection or Inflammation

Outcome Measures

Primary Outcomes (1)

• Number of patients with a hospital re-admission

  Total number of re-admissions after revision fixation over the first 365 days post discharge from the hospitalization for initial surgical treatment of the infected nonunion. Re-admission can be for infection, nonunion, soft tissue revision, line complication, or antibiotic complication.

  1 year

Secondary Outcomes (9)

• Number of patients with treatment failure

  1 year

• Number of patients with a re-hospitalization for a complication

  1 year

• Number of patients with an additional infection

  1 year

• Number of patients that experienced amputation

  1 year

• Medical Costs

  1 year

Study Arms (2)

Standard of Care PO (oral) antibiotics

ACTIVE COMPARATOR

An intervention in this study includes randomization of patients with an infected unhealed fracture to standard of care PO (oral) antibiotics for up to 6 weeks post hospitalization. No medications will be provided by the study. Study participants will be prescribed their oral antibiotics by their treating physician and the specific type will depend on their infection diagnosis. Medications will be obtained using health insurance and/or resources available at the treating facility therefore the mode of antibiotics utilized as standard of care will vary across participating sites. Sites will follow their standard of care delivery for antibiotics, and the study will defer to this standard.

Drug: Standard of Care PO (oral) antibiotics

Standard of Care Intravenous (IV) antibiotics

ACTIVE COMPARATOR

An intervention in this study includes randomization of patients with an infected unhealed fracture to intravenous (IV) antibiotics for up to 6 weeks post hospitalization. No medications will be provided by the study. Study participants will be prescribed their IV antibiotics by their treating physician and the specific type will depend on their infection diagnosis. Medications will be obtained using health insurance and/or resources available at the treating facility therefore the mode of antibiotics utilized as standard of care will vary across participating sites. Sites will follow their standard of care delivery for antibiotics, and the study will defer to this standard.

Drug: Standard of Care Intravenous (IV) antibiotics

Interventions

Standard of Care PO (oral) antibiotics DRUG

An intervention in this study includes randomization of patients with an infected nonunion to PO (oral) antibiotics for up to 6 weeks post hospitalization. The exact type of oral antibiotic will be depended on the patient's infection diagnosis.

Standard of Care PO (oral) antibiotics

Standard of Care Intravenous (IV) antibiotics DRUG

An intervention in this study includes randomization of patients with an infected nonunion to intravenous (IV) antibiotics for up to 6 weeks post hospitalization. The exact type of IV antibiotic will be depended on the patient's infection diagnosis.

Standard of Care Intravenous (IV) antibiotics

Eligibility Criteria

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

You may qualify if:

• \. Bone fracture (proximal to and including the tarsal/metatarsal joint (Lisfranc) or proximal to the carpal joints (includes distal radius fractures), excluding pelvis and spine) that has previously undergone fixation and has not healed and requires fixation to be retained or replaced at least until bone union. Fractures that have not healed and require revision fixation are also eligible.
• Infection as determined by either
• FRI criteria
• CDC criteria (without the timeframe) This includes the possibility of culture negative, but determined to be infection by treating surgeon
• Systemic antibiotic treatment regimen scheduled for at least 6 weeks

You may not qualify if:

• Patients with a high risk of amputation based on the initial managing physician
• Patients undergoing treatment of any other investigational therapy within the month preceding infection treatment or planned within the 12 months following infection treatment
• Incarcerated or institutionalized patients
• Patients who are unable to return for required follow-up visits and/or medical co-morbidities which preclude treatment with a general anesthetic
• Patients with a prior history of chronic infection at the index site before fracture fixation
• Patients with pathological fractures from a neoplastic process
• History of Paget's Disease
• The patient, or a designated proxy, unwilling to provide consent
• The patient must be available for follow-up for at least 12 months following infection treatment

Sponsors & Collaborators

• Major Extremity Trauma Research Consortium: lead
• United States Department of Defense: collaborator

Study Sites (13)

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Maryland , MD Department of Orthopaedics

Baltimore, Maryland, 21201, United States

RECRUITING

Sinai Hospital Baltimore

Baltimore, Maryland, 21215, United States

NOT YET RECRUITING

Hennepin Health

Minneapolis, Minnesota, 55487, United States

RECRUITING

Jamaica Hospital Medical Center

Queens, New York, 11418, United States

NOT YET RECRUITING

Atrium Health, Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

NOT YET RECRUITING

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27106, United States

RECRUITING

University of Okalahoma College of Medicine

Oklahoma City, Oklahoma, 73104, United States

NOT YET RECRUITING

Penn State University M.S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

Vanderbilt Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

NOT YET RECRUITING

University of Washington Harborview Medical Center

Seattle, Washington, 98195, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Infections; Wound Infection; Fractures, Ununited; Leg Injuries; Inflammation; Fractures, Bone

Interventions

Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• William Obremskey, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

• Renan Castillo, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William Obremskey, MD

CONTACT

615-260-2054; william.obremskey@vumc.org

Karen Trochez

CONTACT

karen.m.trochez@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two arm, randomized controlled multicenter Phase III trial

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 26, 2023
• Study Start: May 30, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 29, 2028
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)