Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for Osteomyelitis

NCT02168816 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 206209
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Osteomyelitis

Keywords

Osteomyelitis; Diabetes; Foot Infection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Bone Infection

  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 Outcomes (1)

• Number of Participants With Ulcer Resolution

  Six Months

Study Arms (3)

Midfoot

ACTIVE COMPARATOR

Individuals with an infection on the midfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.

Drug: Intravenous Antibacterial Agent; Drug: Oral Antibacterial Agent

Hindfoot

ACTIVE COMPARATOR

Individuals with an infection on the hindfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.

Drug: Intravenous Antibacterial Agent; Drug: Oral Antibacterial Agent

Toe

ACTIVE COMPARATOR

Individuals with an infection on the toe are randomized to an intravenous antibacterial agent or an oral antibacterial agent.

Drug: Intravenous Antibacterial Agent; Drug: Oral Antibacterial Agent

Interventions

Intravenous Antibacterial Agent DRUG

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.

Also known as: Piperacillin/tazobactam (Zosyn), Cefepime, Metronidazole, Aztreonam, Vancomycin, Daptomycin, Linezolid (Zyvox), Meropenem

Hindfoot; Midfoot; Toe

Oral Antibacterial Agent DRUG

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)

Also known as: Sulfamethoxazole/Trimethoprim (SMX-TMP), Clindamycin (Clindesse), Linezolid (Zyvox), Moxifloxacin (Avelox), Ciprofloxacin (Cetraxal), Metronidazole (Flagyl)

Hindfoot; Midfoot; Toe

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Loyola University: lead

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Related Publications (6)

• Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12):e132-73. doi: 10.1093/cid/cis346.

  PMID: 22619242 BACKGROUND

• Spellberg B, Lipsky BA. Systemic antibiotic therapy for chronic osteomyelitis in adults. Clin Infect Dis. 2012 Feb 1;54(3):393-407. doi: 10.1093/cid/cir842. Epub 2011 Dec 12.

  PMID: 22157324 BACKGROUND

• Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis. 2005 May;9(3):127-38. doi: 10.1016/j.ijid.2004.09.009.

  PMID: 15840453 BACKGROUND

• Bouazza N, Pestre V, Jullien V, Curis E, Urien S, Salmon D, Treluyer JM. Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis. Br J Clin Pharmacol. 2012 Dec;74(6):971-7. doi: 10.1111/j.1365-2125.2012.04292.x.

  PMID: 22486719 BACKGROUND

• Wukich DK, Armstrong DG, Attinger CE, Boulton AJ, Burns PR, Frykberg RG, Hellman R, Kim PJ, Lipsky BA, Pile JC, Pinzur MS, Siminerio L. Inpatient management of diabetic foot disorders: a clinical guide. Diabetes Care. 2013 Sep;36(9):2862-71. doi: 10.2337/dc12-2712.

  PMID: 23970716 BACKGROUND

• Pinzur MS, Gil J, Belmares J. Treatment of osteomyelitis in charcot foot with single-stage resection of infection, correction of deformity, and maintenance with ring fixation. Foot Ankle Int. 2012 Dec;33(12):1069-74. doi: 10.3113/FAI.2012.1069.

  PMID: 23199855 BACKGROUND

MeSH Terms

Conditions

Osteomyelitis; Diabetes Mellitus

Interventions

Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Cefepime; Metronidazole; Aztreonam; Vancomycin; Daptomycin; Linezolid; Meropenem; Anti-Bacterial Agents; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Clindamycin; clindamycin phosphate; Moxifloxacin; Ciprofloxacin

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Penicillanic Acid; Sulfones; Drug Combinations; Pharmaceutical Preparations; Cephalosporins; Thiazines; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Monobactams; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Thienamycins; Carbapenems; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pyrimidines; Lincomycin; Lincosamides; Pyrrolidines; Glycosides; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Limitations and Caveats

The trial was stopped prematurely for feasibility (i.e., low recruitment)

Results Point of Contact

• Title: Michael Pinzur, M.D.
• Organization: Loyola University Medical Center

mpinzu1@lumc.edu

708-216-4993

Study Officials

• Michael Pinzur, M.D.

  Loyola University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 20, 2014
• Study Start: March 19, 2014
• Primary Completion: February 2, 2017
• Study Completion: February 2, 2017
• Last Updated: July 19, 2018
• Results First Posted: June 8, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)