The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001164381
Ethics application status
Approved
Date submitted
29/06/2017
Date registered
8/08/2017
Date last updated
19/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Use of Procalcitonin in Diagnosing and Monitoring Diabetic Foot Osteomyelitis and Cellulitis at The Townsville Hospital–A Pilot Study
Scientific title
Use of Procalcitonin in Diagnosing and Monitoring Diabetic Foot Osteomyelitis and Cellulitis at The Townsville Hospital–A Pilot Study
Secondary ID [1] 292304 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 303845 0
Diabetic Foot infections 303846 0
Foot Ulcer 303847 0
Condition category
Condition code
Infection 303211 303211 0 0
Other infectious diseases
Metabolic and Endocrine 303252 303252 0 0
Diabetes
Skin 303520 303520 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diabetic foot cellulitis will be confirmed histologically through tissue biopsy/debridement (group 1 = 25). Serum procalcitonin levels will be determined using a commercially available enzyme-linked fluorescent assay and will be compared with the histology report as a diagnostic marker at onset of the study and at week 6 and 12 to monitor response to the usual care. Subjects will receive the treatment fortnightly comprising the following as usual care: After debridement, atraumatic dressing and nonadherent absorbent pad will be applied. Antibiotics will be administered based on microscopy, culture, and sensitivity results following deep wound swab and blood cultures. No additional treatment will be offered apart from the usual care.
Intervention code [1] 298480 0
Diagnosis / Prognosis
Comparator / control treatment
Diabetic foot osteomyelitis will be confirmed histologically through tissue biopsy/debridement (group 2 = 25). Serum procalcitonin levels will be determined using a commercially available enzyme-linked fluorescent assay and will be compared with the histology report as a diagnostic marker at onset of the study and at week 6 and 12 to monitor response to the usual care. Subjects will receive the treatment fortnightly comprising the following as usual care: after debridement, atraumatic dressing and nonadherent absorbent pad will be applied. Antibiotics will be administered based on microscopy, culture, and sensitivity results following deep wound swab and blood cultures. No additional treatment will be offered apart from the usual care.
Control group
Active

Outcomes
Primary outcome [1] 302585 0
The serum procalcitonin levels of the patients at week 1 will be computed to determine the most suitable discriminating concentrations to diagnose diabetic foot cellulitis and osteomyelitis based on the gold-standard histologic diagnosis.
Timepoint [1] 302585 0
For diagnostic purpose only week 1 (baseline) serum levels will be used.
Primary outcome [2] 302586 0
Determining serum procalcitonin levels to monitor treatment response of diabetic foot cellulitis and osteomyelitis from week 1 to 12...
Timepoint [2] 302586 0
For monitoring response to treatment of diabetic foot cellulitis and osteomyelitis serum procalcitonin levels at week 1, 6 and 12 will be analysed.
Secondary outcome [1] 336435 0
Cost-effectiveness of using serum procalcitonin in diagnosing diabetic foot cellulitis and osteomyelitis will be expressed as an incremental cost effectiveness ratio and results will be presented in cost effectiveness planes as well as cost-effectiveness acceptability curves. The data will be linked and compared with the hospital cost records.
Timepoint [1] 336435 0
Cost-effectiveness of using serum procalcitonin in monitoring diabetic foot cellulitis and osteomyelitis response to treatment at week 1, 6 and 12.

Eligibility
Key inclusion criteria
Patients meeting the following inclusion criteria will be eligible to enter the study:
1. Subjects with diabetic foot ulcer
2. Aged 18 years or over
3. Exclusion of other etiologies of foot ulcer.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients meeting any of the following criteria will not be included in the study:

1. Clinical infection at the studied ulcer site (bacterial and fungal)
2. Planned surgical intervention for the diabetic foot ulcer
3. Clinically significant lower-extremity ischemia (as defined by an ankle/brachial index of <0.65)
4. Significant medical conditions that would impair wound healing will also be excluded from the study. These conditions include hepatic, respiratory or cardiac failures, aplastic anemia, scleroderma and malignancy, treatment with immunosuppressive agents or steroids, myocardial infarcts, stroke, major surgery within 6 months of the study, or usage of tobacco
5. Ulcer of a non-diabetic pathophysiology (e.g., rheumatoid, radiation-related, and vasculitis-related ulcers, calciphylaxis or dystrophic calcinosis cutis)
6. Active malignancy other than basal cell carcinoma as well as subjects with cancerous or pre-cancerous lesions in the ulcer area
7. Pregnancy
8. Inability to comply with study protocol

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis
Statistical analysis will be performed using the SAS 9.4 statistical package. Differences between the two groups will be tested using parametric or nonparametric methods according to the specific indications. Differences between the laboratory levels of the two groups at baseline will be measured using the Wilcoxon rank sum test in median. Data will be presented as mean +/standard deviation. In addition, analysis of variance for repeated measurements will be performed to test the timing effect of the studied parameters in the follow-up of the patients. The same analysis will be used to examine for differences during follow-up between patients with diabetic foot cellulitis and diabetic foot osteomyelitis. The Greenhouse–Geisser adjustment will be used when the sphericity assumptions are not fulfilled. P values <0.05 will be considered statistically significant.

Cost effectiveness of procalcitonin test will be expressed as an Incremental Cost Effectiveness Ratio (ICER), which will be calculated as incremental costs divided by incremental effects. The results will be presented in cost-effectiveness planes and cost-effectiveness acceptability curves (CEACs). Furthermore, prospective cost savings from use of procalcitonin monitoring foot ulcer healing of the 2 conditions will be conducted using a one-way sensitivity analysis to test the robustness of findings in net savings.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 8457 0
The Townsville Hospital - Douglas
Recruitment postcode(s) [1] 16537 0
4814 - Douglas

Funding & Sponsors
Funding source category [1] 296848 0
University
Name [1] 296848 0
James Cook University
Address [1] 296848 0
Translational Research in Endocrinology and Diabetes [TREAD]
1, James Cook Drive
Douglas, QLD 4811
Country [1] 296848 0
Australia
Primary sponsor type
University
Name
James Cook University
Address
Translational Research in Endocrinology and Diabetes [TREAD]
1 James Cook Drive
Douglas QLD 4811
Country
Australia
Secondary sponsor category [1] 295846 0
Hospital
Name [1] 295846 0
The Townsville Hospital
Address [1] 295846 0
100 Angus Smith Drive, Douglas QLD 4814
Country [1] 295846 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298078 0
The Townsville Hospital and Health Services
Ethics committee address [1] 298078 0
100 Angus Smith Drive, Douglas QLD 4814.
Ethics committee country [1] 298078 0
Australia
Date submitted for ethics approval [1] 298078 0
28/06/2017
Approval date [1] 298078 0
31/10/2017
Ethics approval number [1] 298078 0
31/10/2017

Summary
Brief summary
Diabetic foot bone infection (osteomyelitis) is among the most common causes of leg amputation and prolonged hospitalization among Australians. Early and prompt diagnosis and treatment of osteomyelitis is crucial to reducing hospital admissions and limb amputations. Currently the tests that are used to confirm osteomyelitis are either costly (MRI, bone scan), not readily available at the time of immediate need (MRI) or ineffective (x-ray) in differentiating foot osteomyelitis from soft tissue foot infections (cellulitis). To date no simple laboratory test shown to reliably differentiate the 2 common form of diabetic foot infections –cellulitis and osteomyelitis.

Procalcitonin, a cheap, simple blood test for detecting and monitoring infections in other conditions is thought to be a useful test for diabetic foot infections. Blood level of procalcitonin has been reported to be markedly elevated in bone infections and lower levels in cellulitis. This study is designed to determine the role of procalcitonin in correctly distinguishing diabetic foot cellulitis from osteomyelitis and to assess levels that will be used to monitor response to treatment of both conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75918 0
Prof usman H. Malabu
Address 75918 0
The Townsville Hospital
100 Angus Smith Drive
Douglas
QLD 4814.
Country 75918 0
Australia
Phone 75918 0
+61-7-4433 1111
Fax 75918 0
Email 75918 0
usman.malabu@jcu.edu.au
Contact person for public queries
Name 75919 0
Prof Usman H. Malabu
Address 75919 0
The Townsville Hospital
100 Angus Smith Drive
Douglas
QLD 4814.
Country 75919 0
Australia
Phone 75919 0
+61-7-4433 1111
Fax 75919 0
Email 75919 0
usman.malabu@jcu.edu.au
Contact person for scientific queries
Name 75920 0
Prof Usman H. Malabu
Address 75920 0
The Townsville Hospital
100 Angus Smith Drive
Douglas
QLD 4814.
Country 75920 0
Australia
Phone 75920 0
+61-7-4433 1111
Fax 75920 0
Email 75920 0
usman.malabu@jcu.edu.au

No information has been provided regarding IPD availability
Summary results
No Results