OsteomyelitisPhase 2CRO-OSTEONCT02168816
Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for Osteomyelitis
A Phase 2 study testing Intravenous Antibacterial Agent and Oral Antibacterial Agent in people with Osteomyelitis, run by Loyola University at 1 site in United States.
Trial 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."… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteomyelitis
- What is being tested?
- Intravenous Antibacterial Agent and Oral Antibacterial Agent
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2014to 2 Feb 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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]
Trial locations and contacts
1 site in 1 country.
United States1 site
Loyola University Medical Center
Maywood, Illinois, 60153
About this study
Official title: 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.
Read the 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.
- Conditions
- Osteomyelitis
- Being tested
- Intravenous Antibacterial Agent, Oral Antibacterial Agent
- Keywords
- Osteomyelitis, Diabetes, Foot Infection
- Medical subject headings
- Osteomyelitis, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous Antibacterial AgentDrug
Also called Piperacillin/tazobactam (Zosyn), Cefepime, Metronidazole, Aztreonam
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.
Oral Antibacterial AgentDrug
Also called Sulfamethoxazole/Trimethoprim (SMX-TMP), Clindamycin (Clindesse), Linezolid (Zyvox), Moxifloxacin (Avelox)
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)
| Study group | Role | What they receive |
|---|---|---|
| Midfoot | Active comparator | Individuals with an infection on the midfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent. Receives: 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. Receives: 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. Receives: Drug: Intravenous Antibacterial Agent; Drug: Oral Antibacterial Agent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Six Months
Secondary outcomes (1)
Number of Participants With Ulcer Resolution
Six months following completion of treatment, the researchers record whether each participant's ulcer has resolved.
Measured: Six Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2014 (estimated)
- Study start19 Mar 2014
- Primary completion2 Feb 2017
- Study completion2 Feb 2017
Why it stopped: The study was stopped for feasibility (i.e., low recruitment)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for OsteomyelitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Pinzur, M.D., Loyola University
- Investigators
- Michael Pinzur, M.D., Principal investigator, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02168816
- Sponsor's protocol ID
- 206209
- Acronym
- CRO-OSTEO
- Status last verified
- Jun 2018
- First submitted
- 10 Jun 2014
- Last updated
- 19 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual participant data
Publications
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.
PubMed 22619242Spellberg 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.
PubMed 22157324Lazzarini 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.
PubMed 15840453Bouazza 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.
PubMed 22486719Wukich 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.
PubMed 23970716Pinzur 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.
PubMed 23199855
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for the Treatment of Diabetic Foot Osteomyelitis (CRO-OSTEOMYELITIS)
- ClinicalTrials.gov ID
- NCT02168816
- Acronym / sponsor ID
- CRO-OSTEO / 206209
- Conditions
- Osteomyelitis
- Keywords
- Osteomyelitis, Diabetes, Foot Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped for feasibility (i.e., low recruitment)
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Study start
- 19 Mar 2014 (actual)
- Primary completion
- 2 Feb 2017 (actual)
- Study completion
- 2 Feb 2017 (actual)
- First posted
- 20 Jun 2014 (estimated)
- Results
- Posted 8 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Midfoot | Active comparator | Drug: Intravenous Antibacterial Agent, Drug: Oral Antibacterial AgentIndividuals with an infection on the midfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent. |
| Hindfoot | Active comparator | Drug: Intravenous Antibacterial Agent, Drug: Oral Antibacterial AgentIndividuals with an infection on the hindfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent. |
| Toe | Active comparator | Drug: Intravenous Antibacterial Agent, Drug: Oral Antibacterial AgentIndividuals with an infection on the toe are randomized to an intravenous antibacterial agent or an oral antibacterial agent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (6 listed)
- Absolute neutrophil count (ANC) < 500
- Pregnant or lactating patients
- Patients with organisms resistant to oral therapy
- Internal hardware
- Definitive amputations (BKA)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Antibacterial AgentAlso: Piperacillin/tazobactam (Zosyn), Cefepime, Metronidazole, AztreonamIndividuals 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. | Drug | Hindfoot, Midfoot, Toe |
| Oral Antibacterial AgentAlso: Sulfamethoxazole/Trimethoprim (SMX-TMP), Clindamycin (Clindesse), Linezolid (Zyvox), Moxifloxacin (Avelox)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) | Drug | Hindfoot, Midfoot, Toe |
Primary outcome
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.
1 secondary outcome
Number of Participants With Ulcer Resolution
Time frame: Six Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22619242Lipsky 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.
- Background: PubMed 22157324Spellberg 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.
- Background: PubMed 15840453Lazzarini 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.
- Background: PubMed 22486719Bouazza 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.
- Background: PubMed 23970716Wukich 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.
- Background: PubMed 23199855Pinzur 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.
- Individual participant dataSharing planned: No. There is no plan to share individual participant data
Related trials for Osteomyelitis
Active, not recruiting
Acute Non-severe Osteomyelitis in Children - Outpatient Management Strategy With Oral Antibiotic Therapy Compared to a Standard Strategy With Conventional Hospitalization and Intravenous Antibiotic Therapy: a Randomized Open-label Non-inferiority Study With Bayesian and Medical-economic Analyses.
Osteomyelitis
Recruiting
Antibiotic Device for Osteomyelitis of the Extremities Pivotal Trial - Genex With Gentamicin.
Osteomyelitis
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 4
BonE and Joint Infections - Simplifying Treatment in Children Trial
Bone Infection, Septic Arthritis
Active, not recruiting
Evaluation of the Efficiency of the Bone Substitute Cerament-G Locally Delivering Gentamicin in the Treatment of Chronic Osteomyelitis of Long Bones
Osteomyelitis Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Pinzur, M.D. principal investigator
Loyola University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravenous Antibacterial Agent and Oral Antibacterial Agent in people with Osteomyelitis, run by Loyola University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Bone Infection (time frame: Six Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02168816, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2018.