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Trial registered on ANZCTR


Registration number
ACTRN12612000833864
Ethics application status
Approved
Date submitted
25/07/2012
Date registered
7/08/2012
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing outcomes of oral versus intravenous antibiotic therapy for the treatment of the diabetic foot wound complicated by osteomyelitis
Scientific title
An open-label randomised pilot trial comparing outcomes of oral versus intravenous antibiotic therapy for the treatment of the diabetic foot wound complicated by osteomyelitis
Secondary ID [1] 280886 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic foot osteomyelitis 286956 0
Condition category
Condition code
Infection 287294 287294 0 0
Other infectious diseases
Metabolic and Endocrine 287332 287332 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomly assigned to one of two clinical management strategies. These are:
Comparator treatment: Prolonged intravenous (IV) antibiotic strategy (that is, 6 weeks of intravenous antibiotics) and
Intervention: Early oral antibiotic strategy (that is, early commencement of oral antibiotic therapy for a duration of 6 weeks, following less than two weeks of initial treatment with intravenous antibiotics).
The type of antibiotic and dose (below doses are according to normal renal function) will be determined on a case-by-case basis at the discretion of the treating team. A standardised approach to treat diabetic foot osteomyelitis (using drugs, listed below, with already proven efficacy for this condition) will be followed for participants in both groups. This approach takes into account patient co-morbidities, drug allergies, and microbiology results, such as pathogen susceptibility to specific antimicrobial drugs.
The oral antibiotics may include:
- Clindamycin (450mg orally every 6- 8 hours) PLUS ciprofloxacin (450mg orally every 6-8 hours),
- Co-trimoxazole (Trimethoprim/sulfamethoxazole; 160/800mg x 2 8 hourly to every 12 hours) PLUS metronidazole (400mg orally every 8 hours),
- Rifampicin (300mg orally every 12 hours [or 600mg orally daily]) PLUS fusidic acid (500mg orally every 8-12 hours) PLUS ciprofloxacin (450mg orally every 6-8 hours).

Participants in both groups will continue to receive usual standard care, which may include pressure offloading, wound dressings, revascularisation, and non-surgical sharps debridement.
Intervention code [1] 285318 0
Treatment: Drugs
Comparator / control treatment
The comparator group is the prolonged intravenous (IV) antibiotic strategy for 6 weeks.
The type of antibiotic and dose (below doses are according to normal renal function and administered intravenously) will be determined on a case-by-case basis at the discretion of the treating team. The antibiotics may include:
- Vancomycin (initial starting dose: 1.5g every 12 hours),
- Piperacillin/tazobactam (4.5 g every 6 hours or 18g daily over 24 hour continuous infusion),
- Ertapenem (1g daily),
- Meropenem (1g three times per day or 3g over 24 hour continuous infusion),
- Teicoplanin (initial starting dose of 12mg/kg (800mg) 12 hourly for three doses then maintenance 12mg/kg (800mg) daily).
Control group
Active

Outcomes
Primary outcome [1] 287582 0
Resolution of osteomyelitis as evaluated by the absence of infection and the infection severity grading following examination of clinical signs and symptoms.
Criteria for determining presence of infection will be based on the current recommendations from the Infectious Diseases Society of America and the current consensus document from the International Working Group on the Diabetic Foot.
Grading of infection severity is based on Infectious Diseases Society of America - International Working Group on the Diabetic Foot validated criteria.
Timepoint [1] 287582 0
4 weeks post treatment
Primary outcome [2] 287583 0
Resolution of osteomyelitis as evaluated by plain X-ray
Timepoint [2] 287583 0
4 weeks post treatment
Secondary outcome [1] 298444 0
Percent reduction in wound size
Timepoint [1] 298444 0
Baseline, Week 1 - 6 (treatment period), Week 10 (4 weeks post treatment), Week 14 (8 weeks post treatment) and Week 18 (12 weeks post treatment)
Secondary outcome [2] 298445 0
The clinical utility of using the EuroQol 5D (EQ-5D) for quality of life assessment
Timepoint [2] 298445 0
Baseline, Week 4, Week 18 (12 weeks post treatment)
Secondary outcome [3] 298446 0
Reaching 30 minimum number of participants in a 6 month period
Timepoint [3] 298446 0
Monitored continuously throughout the study
Secondary outcome [4] 298447 0
Completion of study in at least 90% of all recruited participants
Timepoint [4] 298447 0
Monitored continuously throughout the study
Secondary outcome [5] 298519 0
Analysis of costs of oral antibiotic therapy compared to costs of intravenous therapy
Timepoint [5] 298519 0
At completion of study

Eligibility
Key inclusion criteria
18 years or older; currently treated patient at Southern Health; Diagnosis of Type I or Type II diabetes mellitus; Diabetic foot osteomyelitis confirmed on MRI, Plain X-ray and clinical signs and symptoms; adequate macrovascular blood supply; adequate debridement of infected tissue; known pathogen(s); suitable for oral and intravenous antibiotic therapy; two weeks or less of IV antibiotic therapy for diabetic foot osteomyelitis at baseline.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Females that are pregnant or breastfeeding; sepsis at presentation; positive blood culture within 14 days of presentation; inadequate macrovascular supply; amputation of infected limb planned/performed; pathogen unknown; known pathogens resistant to appropriate oral and/or IV antibiotics included in treatement strategy; more than 14 days of IV antibiotic therapy prior to baseline; allergy or other absolute contraindication to the oral and/or IV antibiotics listed in treatment strategy; implant or prosthetic device in infected limb; has another condition that requires treatment with antibiotics for greater than one week prior to baseline.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Potential participants will be identified by their treating team. These patients will be approached about the study and provided with a Participant Information and Consent form if they are interested. If they are agreeable to participating, participants will be allocated the next available study number by the research coordinator. This number will correspond with a sealed opaque envelope containing one of two clinical management strategies (oral or IV). This is an open-label study, therefore once the treatment group has been assigned, the participant, their treating team and the researchers will be aware of the treatment group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by a computer program. This will be conducted by an individual who is not directly involved in this research project. Once a participant is enrolled in the study, they will be assigned the next available study number. The study numbers will be randomly assigned to a treatment group that will be recorded in sealed opaque envelopes labelled with the corresponding study number.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/08/2012
Actual
3/09/2012
Date of last participant enrolment
Anticipated
Actual
4/04/2014
Date of last data collection
Anticipated
4/04/2014
Actual
10/04/2014
Sample size
Target
50
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 285683 0
Hospital
Name [1] 285683 0
Southern Health
Country [1] 285683 0
Australia
Funding source category [2] 285684 0
Commercial sector/Industry
Name [2] 285684 0
Novo Nordisk Pharmaceutical Pty Ltd
Country [2] 285684 0
Australia
Primary sponsor type
Hospital
Name
Southern Health
Address
Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 284512 0
None
Name [1] 284512 0
Address [1] 284512 0
Country [1] 284512 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287670 0
Southern Health Human Research Ethics Committee
Ethics committee address [1] 287670 0
Research Directorate
Southern Health
Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Ethics committee country [1] 287670 0
Australia
Date submitted for ethics approval [1] 287670 0
Approval date [1] 287670 0
18/07/2012
Ethics approval number [1] 287670 0
12018A

Summary
Brief summary
This pilot study aims to evaluate the feasibility of the methods and procedures used in order to guide a larger open-label randomised trial. In addition, this pilot study will examine the primary outcome measures and the ability to recruit 50 participants in a 6-month period. This study will also involve a cost analysis to compare the cost attributed to both groups.
The study aims to measure and compare clinical outcomes for two clinical management strategies for the treatment of diabetic foot osteomyelitis, these are a) prolonged IV treatment and b) early commencement of oral antibiotic therapy (following a brief initial treatment with IV antibiotics); and to compare the quality of life of participants receiving prolonged treatment with an oral antibiotic strategy and those receiving prolonged treatment with an intravenous antibiotic strategy.
Data regarding the infection (presence or absence and infection severity), the wound size and the participant’s quality of life will be collected at various time-points. There will also be three follow up visit at 4 weeks, 8 weeks and 12 weeks post cessation of antibiotic treatment, which will evaluate the infection (presence or absence and infection severity grade) and the wound size. Whilst an additional plain X-ray will be performed at 4 weeks post cessation of treatment in order to determine if the infection has resolved.
The tentative hypothesis for the pilot study is that a treatment strategy of predominantly oral antibiotics with high oral bioavailability and expected high bone concentration will have a success rate equivalent to that of a strategy of six weeks of intravenous antibiotics, but a lower rate of major complications, a lower cost and a better quality of life.
Although this pilot study will not formally test these hypotheses it will enable the researchers to assess the ability of these hypotheses to be formally tested in a future definitive randomised controlled trial.
Trial website
Trial related presentations / publications
Public notes
Trial has been ceased

Contacts
Principal investigator
Name 34466 0
Dr Jennifer Wong
Address 34466 0
Diabetes Unit
Monash Health
Level 2, 105 David St, Dandenong Victoria 3175
Country 34466 0
Australia
Phone 34466 0
+61 3 95541550
Fax 34466 0
Email 34466 0
[email protected]
Contact person for public queries
Name 17713 0
Dr Dr Jennifer Wong
Address 17713 0
Dandenong Diabetes Unit, Southern Health
Dandenong Hospital
Level 2, 105 David Street
Dandenong VIC 3175
Country 17713 0
Australia
Phone 17713 0
+61 3 9554 1550
Fax 17713 0
+61 3 9554 1544
Email 17713 0
[email protected]
Contact person for scientific queries
Name 8641 0
Dr Dr Jennifer Wong
Address 8641 0
Dandenong Diabetes Unit, Southern Health
Dandenong Hospital
Level 2, 105 David Street
Dandenong VIC 3175
Country 8641 0
Australia
Phone 8641 0
+61 3 9554 1550
Fax 8641 0
+61 3 9554 1544
Email 8641 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.