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

NCT ID: NCT05699174

Last Updated: 2025-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-30

Study Completion Date

2027-09-29

Brief Summary

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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.

Detailed Description

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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.

The specific Aims of this study are to:

Specific Aim 1. Evaluate the effect of treatment of infected nonunion in bone fractures treated with revision fixation and either: (Group 1) operative debridement and PO antibiotic suppression for 6 weeks; or (Group 2) operative debridement and 6 weeks IV antibiotics.

Primary Hypothesis 1a: The rate of re-hospitalization for injury-related complication by one year in Group 1 will be non-inferior to the rate in Group 2.

Hypothesis 1b:. The rate of treatment failure by one year in Group 1 will be non-inferior to the rate in Group 2.

Hypothesis 1c: The rate of persistent infection by one year in Group 1 will be non-inferior to the rate in Group 2.

Hypothesis 1d: The rate of persistent nonunion by one year in Group 1 will be non-inferior to the rate in Group 2.

Hypothesis 1e: The rate of amputation by one year in Group 1 will be non-inferior to the rate in Group 2. Hypothesis 1f: Per patient total costs at 1 year will be lower in Group 1 than in Group 2.

Hypothesis 1g: Compliance in Group 1 will be non-inferior to compliance in Group 2.

Specific Aim 2. Build and validate a risk prediction model for failure of treatment of infected nonunion after fixation of fractures.

Hypothesis 2a: Demographic and injury characteristics will be highly predictive of treatment failure.

Hypothesis 2b: Open fractures will have a higher treatment failure rate than closed fractures.

Hypothesis 2c: Lower extremity fractures will have a higher treatment failure rate than upper extremity fractures.

Hypothesis 2d: Multiple organism infections will have a higher treatment failure rate than single organism infections.

Hypothesis 2e: Gram positive infections will have a higher treatment failure rate than gram negative infections.

Hypothesis 2f: Revision fixation with IMN and treatment failure will be non-inferior to the rate of treatment failure in revision fixation with plates.

Hypothesis 2g: Revision fixation with external fixation and treatment failure will be non-inferior to the rate of treatment failure in revision fixation with IMN or plates.

Hypothesis 2h: One Stage revision fixation strategies will be non-inferior to the rate of treatment failure in Two Staged revision fixation strategies

Study design: At time of treatment for infected nonunion, patients will be randomized to oral (PO) antibiotics group or intravenous (IV) antibiotics group. Patients will receive PO or IV antibiotics for 6 weeks at discharge from the hospitalization to treat the infected nonunion. Both groups will otherwise receive standard care treatment by attending orthopedic surgeon and healthcare team, including debridement and soft tissue coverage of wounds; laboratory evaluation of inflammatory markers at 2 weeks, and 6 weeks; clinical follow at 2 weeks, 6 weeks, 3 months, 6 months, and 12 months to assess recurrence of wound infection; and radiographic follow up at 6 weeks and 3 months or until boney union is confirmed.

Follow-Up: Assessments at baseline and at 2 weeks, 6 weeks, 3 months, 6 months and 12 months following hospital discharge will determine rates of re-hospitalization, treatment failure, infection, nonunion and amputation and patient compliance with antibiotic treatment.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two arm, randomized controlled multicenter Phase III trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard of Care PO (oral) antibiotics

An intervention in this study includes randomization of patients with an infected nonunion 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.

Group Type ACTIVE_COMPARATOR

Standard of Care PO (oral) antibiotics

Intervention Type 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 Intravenous (IV) antibiotics

An intervention in this study includes randomization of patients with an infected nonunion 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.

Group Type ACTIVE_COMPARATOR

Standard of Care Intravenous (IV) antibiotics

Intervention Type 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.

Interventions

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Standard of Care PO (oral) antibiotics

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.

Intervention Type DRUG

Standard of Care Intravenous (IV) antibiotics

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Nonunion of a fracture that has previously undergone fixation. A Nonunion is defined as unplanned surgery with the primary purpose to promote union based on clinical/radiographic evidence \>3 months after last fixation
2. Infection as determined by either

1. FRI criteria
2. CDC criteria (without the timeframe) This includes the possibility of culture negative, but determined to be infection by treating surgeon
3. Systemic antibiotic treatment regimen scheduled for at least 6 weeks

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

Major Extremity Trauma Research Consortium

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William Obremskey, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt Medical Center

Renan Castillo, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Bloomberg School of Public Health

Locations

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Indiana University

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Maryland , MD Department of Orthopaedics

Baltimore, Maryland, United States

Site Status RECRUITING

Hennepin Health

Minneapolis, Minnesota, United States

Site Status NOT_YET_RECRUITING

NYU Langone Medical Center

New York, New York, United States

Site Status RECRUITING

Atrium Health, Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status NOT_YET_RECRUITING

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Penn State University M.S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

University of Washington Harborview Medical Center

Seattle, Washington, United States

Site Status NOT_YET_RECRUITING

University of Wisconsin

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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William Obremskey, MD

Role: CONTACT

615-260-2054

Karen Trochez

Role: CONTACT

Facility Contacts

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Lauren Hill, BS

Role: primary

Yasmin Degani, MPH

Role: primary

Olutayo Alese

Role: primary

612-873-4634

Ivanka Bhambhani

Role: primary

Christine Churchill

Role: primary

Martha Holden

Role: primary

Andrea Myers, BSN

Role: primary

Karen Trochez

Role: primary

Jessica Schisel

Role: primary

Brittany Grasso

Role: primary

Other Identifiers

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W81XWH2210635

Identifier Type: -

Identifier Source: org_study_id

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