PO vs IV Antibiotics for the Treatment of Infected Nonunion of Fractures After Fixation
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Standard of Care PO (oral) antibiotics, Standard of Care Intravenous (IV) antibiotics.
- Who it may be relevant to
- Registry conditions: Infections, Infected Wound, Nonunion of Fracture, Injury Leg. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
PO Versus IV Antibiotics for the Treatment of Infected Nonunion of Fractures After Fixation
Overview
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
This is a Phase III clinical randomized control trial to investigate differences between patients with infected unhealed fracture treated by PO vs. IV antibiotics. The study population will be 250 patients, 18 years or older, being treated for infected unhealed fracture 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 unhealed fracture 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, timing of being unhealed, 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 fractures that have not yet healed 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 unhealed fractures 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 and not healed fractures, 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 unhealed fracture. 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.
Interventions
- Drug 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. - 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.
Primary outcome measures
- Number of patients with a hospital re-admission [Time frame: 1 year]
Secondary outcome measures (9)
- Number of patients with treatment failure [Time frame: 1 year]
- Number of patients with a re-hospitalization for a complication [Time frame: 1 year]
- Number of patients with an additional infection [Time frame: 1 year]
- Number of patients that experienced amputation [Time frame: 1 year]
- Medical Costs [Time frame: 1 year]
- Patient Reported Outcomes [Time frame: 1 year]
- Physical and Psychosocial Function Assessment [Time frame: 1 year]
- Adherence [Time frame: 6 months]
- Compliance [Time frame: 6 months]
Eligibility criteria
Inclusion criteria
- 1\. 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 13 centers
- Indiana University — Indianapolis
- University of Maryland , MD Department of Orthopaedics — Baltimore
- Sinai Hospital Baltimore — Baltimore
- Hennepin Health — Minneapolis
- Jamaica Hospital Medical Center — Queens
- Atrium Health, Carolinas Medical Center — Charlotte
- Wake Forest University Baptist Medical Center — Winston-Salem
- University of Okalahoma College of Medicine — Oklahoma City
- … and 5 more centers
Identifiers
NCT: NCT05699174 · W81XWH2210635