Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001221549
Ethics application status
Approved
Date submitted
5/11/2015
Date registered
9/11/2015
Date last updated
3/09/2019
Date data sharing statement initially provided
3/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Management of Chronic Diabetic Foot Ulcer by Extracorporeal Shockwave Therapy at The Townsville Hospital
Scientific title
Efficacy of Extracorporeal Shockwave Therapy for Management of Diabetic Foot Ulcer at The Townsville Hospital
Secondary ID [1] 287795 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 296676 0
Diabetic Foot Ulcer 296677 0
Condition category
Condition code
Metabolic and Endocrine 296904 296904 0 0
Diabetes
Skin 296905 296905 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Twenty five subjects with diabetic foot ulcer will be treated fortnightly with standard 20-minute wound care (debridement and normal saline dressing) first, to be followed by 10 minutes of shockwave therapy for a period of 6 weeks. A handheld shockwave device will be applied gently against the ulcer surface by treating podiatrist to deliver 300 + 100/cm2 impulses of shockwave at 0.11 mJ/cm2 energy flux density during which the participant may feel light vibration and then crossover for another 6 weeks on fortnightly standard wound care alone with total duration of the study period of 12 weeks. Log of device use time will be utilized to monitor adherence of the shockwave therapy.
Intervention code [1] 293193 0
Treatment: Other
Intervention code [2] 293194 0
Treatment: Devices
Comparator / control treatment
Twenty five subjects with diabetic foot ulcer will be treated with 20-minute standard wound care (debridement and normal saline dressing) fortnightly for a period of 6 weeks and then crossover for another 6 weeks on fortnightly 300 + 100/cm2 impulses of shockwave at 0.11 mJ/cm2 energy flux density to be applied evenly to the ulcer surface in addition to standard wound care alone giving a total duration of the study period of 12 weeks.
Control group
Active

Outcomes
Primary outcome [1] 296518 0
Partial or complete foot ulcer healing to be assessed fortnightly using specialized 3-D camera
Timepoint [1] 296518 0
Fortnightly assessment at the time of treatment for the 12-week study period
Secondary outcome [1] 318656 0
Proportion of participants who achieve a significant (20%) reduction of serum levels if interleukin 6 (IL-6)
Timepoint [1] 318656 0
Completion of the 12-week study

Eligibility
Key inclusion criteria
1. Diabetes age >18 years
2. Stable documented diabetic foot ulcer of full-thickness skin defect requiring >14 days of healing.
3. Exclusion of other etiologies of foot ulcer.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current index foot ulcer of any non-diabetic pathophysiology (e.g. rheumatoid, radiation-related, vasculitis-related, calciphylaxis, or dystrophic calcinosis cutis, etc.).
2. Any major surgery up to 4 weeks prior to the day of enrolment or any planned surgery prior to study completion including any major surgical intervention for the diabetic foot ulcer.
3. Significant medical conditions that potentially impair wound healing and/or alter the concentration of serum immune markers including hepatic, respiratory or cardiac failure, aplastic anemia, autoimmune diseases (e.g. Lupus erythematodes, scleroderma, etc.), chronic inflammatory diseases (e.g. inflammatory bowel disease, inflammatory or rheumatoid arthritis, etc.) and any active malignancies including cancerous or pre-cancerous lesions in the ulcer area other than basal cell carcinoma.
4. Treatment with normothermic or hyperbaric oxygen therapy.
5. Skin and dermal substitutes within 30 days prior to study enrolment.
6. Enzymatic debridement treatment.
7. Participation in any other clinical trial.
8. Inability to comply with study protocol.

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)
All subjects who fit the selection criteria will be invited to participate, and if willing will be provided with information on the study and participant consent will be obtained and then randomized. Patients in each stratum will be assigned numbers using a central stratified randomization scheme.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization list will be prepared by an independent statistician by the method of computer-generated random numbers for each treatment. Patients in each stratum will be assigned numbers using a central stratified randomization scheme designed to provide 1:1 of patients in the 2 groups. Patients will be randomized to initial standard care + shockwave to be followed by standard care alone for another 6 weeks. The other group will have first 6 weeks of standard care alone to be followed by 6 weeks of both shockwave therapy and standard care.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The appropriate sample size was attained by assuming an anticipated difference in wound healing time of 12% (=66 days from an assumed mean of 75 days for diabetic foot ulcer patients at week 12 between the intervention and control group and a within patient variability (standard deviation) of 10days. A power set to 80% yields a calculated sample size of 22 patients per arm. Adding an additional estimated attrition rate of close to 15% = 3 patients per arm leads to an overall planned sample size of 25 patients per arm, and 50 patients in total.

Descriptive statistics including frequency tables and graphs will be provided for all variables, as well as for the changes from baseline within each treatment and the differences between the treatment groups at each visit. All data will be analysed using SPSS Version 22. Tests for normality will be performed and based on the outcome, parametric or nonparametric tests will be employed to determine the differences between the groups. The results will be given as mean + standard deviation. Chi-squared analysis will be performed for categorical variables and student T test or Mann Whitney U test will be carried out for continuous variables for parametric or non-parametric data respectively. ANOVA will be used for determining differences among multiple groups. A p value <0.05 will be considered significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2016
Actual
2/01/2017
Date of last participant enrolment
Anticipated
4/10/2019
Actual
Date of last data collection
Anticipated
10/01/2020
Actual
Sample size
Target
50
Accrual to date
46
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 4564 0
The Townsville Hospital - Douglas
Recruitment postcode(s) [1] 12180 0
4814 - Douglas

Funding & Sponsors
Funding source category [1] 292327 0
Government body
Name [1] 292327 0
Queensland Government Department of Health
Country [1] 292327 0
Australia
Primary sponsor type
Hospital
Name
The Townsville Hospital
Address
100 Angus Smith Drive
Douglas
QLD 4814
Country
Australia
Secondary sponsor category [1] 291002 0
None
Name [1] 291002 0
Address [1] 291002 0
Country [1] 291002 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293794 0
Townsville Hospital and Health Service Human Resaerch Ethics Committee
Ethics committee address [1] 293794 0
100 Angus Smith Drive
Douglas
QLD 4814
Ethics committee country [1] 293794 0
Australia
Date submitted for ethics approval [1] 293794 0
28/04/2015
Approval date [1] 293794 0
30/07/2015
Ethics approval number [1] 293794 0
-

Summary
Brief summary
Extracorporeal shockwave therapy (ESWT) is a new technology in the care of chronic non-healing wounds. The technology delivers high-energy pressure waves into the wound thereby enriching the ulcer with adequate blood through formation of new blood vessels. It also inhibits infection with its antibacterial property. Furthermore, it stimulates the body to produce natural growth factors which helps in repairing the damaged tissues of the wound. Recently, ESWT was reported to be effective in the initiation and acceleration of wound healing in various clinical settings including longstanding diabetic foot ulcers. The effectiveness of ESWT in wound healing, especially in treatment of diabetic foot ulcers has been demonstrated in numerous trials (1-2). It has been shown to be more effective value for money compared to hyperbaric oxygen therapy in management of chronic diabetic wounds (3). There are evidences demonstrating reduced length of stay for admitted patients when using this treatment model (3-4). Its safety profile has been proven in various studies (1-4). Numerous scientific investigations have been conducted on biological mechanism of action of ESWT in animals and humans and both proved to be safe and effective (5-6). Furthermore, it has been demonstrated that ESWT therapy achieves long-term healing results in diabetic wound care (7). Thus using this technology at The Townsville Hospital would likely improve the weighted activity unit per bed day figure for medical patients by increasing the total bed days saved, as that capacity will be filled by current access block / unmet demand of the chronic diabetic foot wounds at the hospital.

In spite of these facts, ESWT technology has not been utilised in the care of diabetic foot ulcer patients in Australia in general and at The Townsville Hospital in particular. This is despite the fact that this technology is non-invasive, simple to use, well tolerated by patients, and only needs to be administered on fortnightly basis whereas even more invasive therapies need more frequent administration. Furthermore, ESWT is applied through an unfocused applicator which assures an almost painless treatment with no anaesthesia required and each therapy session only taking about 10 to 30 minutes.

The main objective of this study was to evaluate wound healing rate and anti-inflammatory effect of shockwave therapy in subjects with diabetic foot ulcer at the Townsville Hospital, Australia.

References
1. Wang C, Kuo Y, Wu R et al. J Surg Res. 2009; 152: 96-103.
2. Moretti B, Notarnicola A. et al. BMC Musculoskeletal Disorders 2009, 10:54, 1-8.
3. Wang CJ, Wu RW, Yang YJ. Diabetes Res Clin Pract. 2011 ;92(2):187-93.
4. Saggini R, Figus A, et al.. Ultrasound Med Biol. 2008 Aug;34(8):1261-71.
5. Mittermayr R, Antonic V, et al. Wound Repair Regen. 2012;20(4):456-65.
6. Kuo YR, Wang CT, et al. Wound Repair Regen. 2009;17(4):522-30.
7. Wang CJ et al. J Surg Res. 2014;189(2):366-72.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39414 0
Prof Usman H. Malabu
Address 39414 0
The Townsville Hospital
100 Angus Smith Drive
Douglas
QLD 4814
Country 39414 0
Australia
Phone 39414 0
+61-7-4433 1111
Fax 39414 0
+61-7-4433 2239
Email 39414 0
[email protected]
Contact person for public queries
Name 39415 0
Prof Usman H. Malabu
Address 39415 0
The Townsville Hospital
100 Angus Smith Drive
Douglas
QLD 4814.
Country 39415 0
Australia
Phone 39415 0
+61-7-4433 1111
Fax 39415 0
+61-7-4433 2239
Email 39415 0
[email protected]
Contact person for scientific queries
Name 39416 0
Prof Usman H. Malabu
Address 39416 0
The Townsville Hospital
100 Angus Smith Drive
Douglas
QLD 4814.
Country 39416 0
Australia
Phone 39416 0
+61-7-4433 1111
Fax 39416 0
+61-7-4433 2239
Email 39416 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Deidentified, individual participant data underlying published results only
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication
Available to whom?
researchers who provide a methodologically sound proposal
Available for what types of analyses?
for IPD meta-analyses, etc.
How or where can data be obtained?
[email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
4315Study protocol  [email protected]
4316Statistical analysis plan  [email protected]
4317Ethical approval  [email protected]
4318Informed consent form  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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