Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for Osteomyelitis (CRO-OSTEO)

June 20, 2018 updated by: Michael Pinzur, M.D., Loyola University

Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for the Treatment of Diabetic Foot Osteomyelitis (CRO-OSTEOMYELITIS)

The Infectious Diseases Society of America (IDSA) 2012 guidelines for the diagnosis and treatment of diabetic foot infections state that for the treatment of diabetic foot osteomyelitis "No data support the superiority of any specific antibiotic agent or treatment strategy, route, or duration of therapy." Traditionally, osteomyelitis has been treated with a long course of intravenous antibiotics, generally six weeks. Oral antibiotics with high bioavailability and adequate bone penetration have been shown in published studies to be effective for the treatment of osteomyelitis.

The investigators propose to conduct a prospective, single-center, randomized, open trial at Loyola University Medical Center (LUMC) comparing the efficacy of oral antibiotic therapy to intravenous (IV) antibiotic therapy for the treatment of diabetic foot osteomyelitis. The investigators hypothesize that oral antibiotic therapy is equivalent to IV antibiotic therapy. Bone/tissue cultures are obtained for all patients for clinical purposes and are sent to pathology for histologic examination and to the clinical microbiology laboratory for culture and susceptibility. Patients will receive six weeks of IV or oral antibiotic therapy depending upon their randomization group. Primary outcomes at six months clinical follow-up will include: (i) no evidence of bone infection and (ii) resolution of ulcer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Currently, available literature is not adequate to determine the best agent, route, or duration of antibiotic therapy for the treatment of chronic osteomyelitis. The standard of therapy has been to treat patients with a parenteral antibiotic for four to six weeks. In a recent literature review by Spellberg et al. it was concluded that oral and parenteral antibiotic therapy have similar cure rates for the treatment of chronic osteomyelitis. Oral antibiotic therapy is associated with a lower risk to the patient due to avoiding the need of a central IV line. Additionally, oral therapy costs less than a course of IV antibiotics. Oral antibiotics with high bioavailability and good bone penetration include, fluoroquinolones, linezolid, trimethoprim/sulfamethoxazole (2 tabs bid), clindamycin and metronidazole. These antibiotics have been shown in recent studies to obtain levels in the bone that exceed the minimum inhibitory concentration (MIC) levels of the targeted organisms. According to the IDSA 2012 guidelines for the treatment of diabetic foot infections, the diagnosis of osteomyelitis can be made via plain radiographs or MRI imaging (more sensitive). A bone scan can be considered if an MRI cannot be done. The preferred method of diagnosis is by bone culture and histology. The guidelines also recommend surgical debridement to healthy tissue for diabetic foot infections followed by antibiotic therapy.

The Purpose of this study is to compare the efficacy of oral antibiotic therapy with intravenous antibiotic therapy for the treatment of diabetic foot osteomyelitis following surgical debridement. They hypothesis is that oral antibiotic therapy is equivalent to intravenous antibiotic therapy for the treatment of diabetic foot osteomyelitis.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 years of age and older
  • Diagnosis of Diabetes Mellitus (per past medical history documented in the patient medical record)
  • Foot osteomyelitis (distal to ankle)
  • Surgical debridement (in operating room)

Exclusion Criteria:

  • Absolute neutrophil count (ANC) < 500
  • Pregnant or lactating patients
  • Patients with organisms resistant to oral therapy
  • Internal hardware
  • Definitive amputations (BKA)
  • Limb ischemia [absent pedal pulses or ankle-brachial index (ABI) < 0.5]

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Midfoot
Individuals with an infection on the midfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Drug: Intravenous Antibacterial Agent
Individuals in this arm receive an intravenous antibacterial agent. They are not assigned to specific medications. Individuals in this arm will receive an intravenous antibacterial agent as determined by their primary healthcare provider. This therapy is usually one of the following intravenous medications: (i) piperacillin/tazobactam (Zosyn), (ii) cefepime, (iii) metronidazole, (iv) aztreonam, (v) vancomycin, (vi) daptomycin, (vii) linezolid (Zyvox), and/or (viii) meropenem.
Other Names:
  • Daptomycin
  • Metronidazole
  • Cefepime
  • Meropenem
  • Vancomycin
  • Aztreonam
  • Piperacillin/tazobactam (Zosyn)
  • Linezolid (Zyvox)
Drug: Oral Antibacterial Agent
Individuals in this arm receive an oral antibacterial agent. They are not assigned to specific medications. Individuals in this arm will receive an oral antibacterial agent as determined by their primary healthcare provider. This therapy is usually one of the following oral medications: (i) sulfamethoxazole/trimethoprim (SMX-TMP), (ii) clindamycin (Clindesse), (iii) linezolid (Zyvox), (iv) moxifloxacin (Avelox), (v) ciprofloxacin (Cetraxal), and/or (vi) metronidazole (Flagyl)
Other Names:
  • Linezolid (Zyvox)
  • Sulfamethoxazole/Trimethoprim (SMX-TMP)
  • Clindamycin (Clindesse)
  • Moxifloxacin (Avelox)
  • Ciprofloxacin (Cetraxal)
  • Metronidazole (Flagyl)
Active Comparator: Hindfoot
Individuals with an infection on the hindfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Drug: Intravenous Antibacterial Agent
Individuals in this arm receive an intravenous antibacterial agent. They are not assigned to specific medications. Individuals in this arm will receive an intravenous antibacterial agent as determined by their primary healthcare provider. This therapy is usually one of the following intravenous medications: (i) piperacillin/tazobactam (Zosyn), (ii) cefepime, (iii) metronidazole, (iv) aztreonam, (v) vancomycin, (vi) daptomycin, (vii) linezolid (Zyvox), and/or (viii) meropenem.
Other Names:
  • Daptomycin
  • Metronidazole
  • Cefepime
  • Meropenem
  • Vancomycin
  • Aztreonam
  • Piperacillin/tazobactam (Zosyn)
  • Linezolid (Zyvox)
Drug: Oral Antibacterial Agent
Individuals in this arm receive an oral antibacterial agent. They are not assigned to specific medications. Individuals in this arm will receive an oral antibacterial agent as determined by their primary healthcare provider. This therapy is usually one of the following oral medications: (i) sulfamethoxazole/trimethoprim (SMX-TMP), (ii) clindamycin (Clindesse), (iii) linezolid (Zyvox), (iv) moxifloxacin (Avelox), (v) ciprofloxacin (Cetraxal), and/or (vi) metronidazole (Flagyl)
Other Names:
  • Linezolid (Zyvox)
  • Sulfamethoxazole/Trimethoprim (SMX-TMP)
  • Clindamycin (Clindesse)
  • Moxifloxacin (Avelox)
  • Ciprofloxacin (Cetraxal)
  • Metronidazole (Flagyl)
Active Comparator: Toe
Individuals with an infection on the toe are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Drug: Intravenous Antibacterial Agent
Individuals in this arm receive an intravenous antibacterial agent. They are not assigned to specific medications. Individuals in this arm will receive an intravenous antibacterial agent as determined by their primary healthcare provider. This therapy is usually one of the following intravenous medications: (i) piperacillin/tazobactam (Zosyn), (ii) cefepime, (iii) metronidazole, (iv) aztreonam, (v) vancomycin, (vi) daptomycin, (vii) linezolid (Zyvox), and/or (viii) meropenem.
Other Names:
  • Daptomycin
  • Metronidazole
  • Cefepime
  • Meropenem
  • Vancomycin
  • Aztreonam
  • Piperacillin/tazobactam (Zosyn)
  • Linezolid (Zyvox)
Drug: Oral Antibacterial Agent
Individuals in this arm receive an oral antibacterial agent. They are not assigned to specific medications. Individuals in this arm will receive an oral antibacterial agent as determined by their primary healthcare provider. This therapy is usually one of the following oral medications: (i) sulfamethoxazole/trimethoprim (SMX-TMP), (ii) clindamycin (Clindesse), (iii) linezolid (Zyvox), (iv) moxifloxacin (Avelox), (v) ciprofloxacin (Cetraxal), and/or (vi) metronidazole (Flagyl)
Other Names:
  • Linezolid (Zyvox)
  • Sulfamethoxazole/Trimethoprim (SMX-TMP)
  • Clindamycin (Clindesse)
  • Moxifloxacin (Avelox)
  • Ciprofloxacin (Cetraxal)
  • Metronidazole (Flagyl)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Bone Infection
Time Frame: Six Months
Six months following completion of treatment, the researchers record evidence of bone infection for each participant. A negative diagnosis is made when there is (i) an absence of infection based on clinical examination and (ii) down-trending of inflammatory markers. Otherwise, a positive diagnosis is made.
Six Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Ulcer Resolution
Time Frame: Six Months
Six months following completion of treatment, the researchers record whether each participant's ulcer has resolved.
Six Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Investigators

  • Principal Investigator: Michael Pinzur, M.D., Loyola University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 19, 2014

Primary Completion (Actual)

February 2, 2017

Study Completion (Actual)

February 2, 2017

Study Registration Dates

First Submitted

June 10, 2014

First Submitted That Met QC Criteria

June 19, 2014

First Posted (Estimate)

June 20, 2014

Study Record Updates

Last Update Posted (Actual)

July 19, 2018

Last Update Submitted That Met QC Criteria

June 20, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 206209

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is no plan to share individual participant data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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