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Trial registered on ANZCTR


Registration number
ACTRN12618002033224
Ethics application status
Approved
Date submitted
26/11/2018
Date registered
19/12/2018
Date last updated
11/07/2019
Date data sharing statement initially provided
19/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effectiveness of Plurogel (Registered Trademark) on Diabetic Foot Ulcers (DFUs) complicated by biofilms in vivo: Proof of concept
Scientific title
The effectiveness of Plurogel (Registered Trademark) on Diabetic Foot Ulcers (DFUs) complicated by biofilms in vivo: Proof of concept
Secondary ID [1] 296673 0
None
Universal Trial Number (UTN)
U1111-1224-3557
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic foot ulcers 310514 0
Condition category
Condition code
Metabolic and Endocrine 309228 309228 0 0
Diabetes
Skin 309472 309472 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants with a chronic (>6 weeks duration) diabetic foot ulcer (DFU) will have a wound hydrogel, Plurogel (Poloxamer P188) applied to their wound three times per week. Treating podiatrists will apply the Plurogel twice weekly, and the other application day will either be self-administered or undertaken by the community nursing team. This frequency of application will ensure that adequate wound coverage with the Plurogel is achieved, and it will also allow regular review of the wound.
The amount of Plurogel required per patient is variable. The surface area size of the DFU will detrmine the amount of Plurogel applied to each wound.
Wound evaluation and wound swabs will be performed at each visit, and 3 tissue biopsies will be taken over the treatment period. The treatment period will be for a maximum of 6 weeks, or less should the wound heal prior. At the end of the study treatment period, participants will continue to receive standard treatment as is appropriate for their DFU.
Intervention code [1] 312999 0
Treatment: Devices
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 308213 0
% of Diabetic foot ulcers (DFUs) healed at 12 weeks, as assessed by changes in the size and appearance of the wound. 3D wound measurements will be taken at each visit time point using an eKare wound camera.
Timepoint [1] 308213 0
Patients will be followed weekly for care in the high risk foot clinic. During each visit wound assessments and observations will be recorded for clinical purposes as per standard care. Wound photographs will be obtained using the eKare system. If its determined the wound has reduced by 50% prior to Week 6 (end of treatment period), this will initiate an earlier study completion timepoint.
Primary outcome [2] 308214 0
We will assess the total microbial load of DFUs before, during and after treatment using real-time qPCR. This molecular approach will amplify all bacterial DNA and human DNA within the tissue samples. From this we can quantify the level of bacterial to human DNA ratio and express as log transformed value. We will also utilise 16S rRNA sequencing to explore the microbiome of DFUs. Bacterial genera will be identified and any genera of interest will be discussed.
Timepoint [2] 308214 0
Day 0, Day 21 (or earlier if wound has reduced by 50% prior) and Day 42.
Secondary outcome [1] 354246 0
We will use Scanning Electron Microscopy (SEM) to confirm the presence of of biofilm in DFUs pre-treatment. We will also use SEM to assess for changes to biofilm architecture with exposure to our intervention agent. We will use an arbitrary scoring system (Han et al 2009) to determine "how much" biofilm is located within tissue samples. To do this we will take 5 separate slices from each tissue sample and observe the mean amount of biofilm as a reflective marker of intervention efficacy.
Timepoint [1] 354246 0
Day 0, Day 21 (or earlier if wound has reduced by 50% prior) and Day 42.

Eligibility
Key inclusion criteria
Type 1 or Type 2 Diabetes Mellitus.
Chronic, non-healing diabetic foot ulcer (DFU) (with or without signs of chronic infection).
A neuroischemic or neuropathic DFU.
ABI >0.4
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
New acute diabetic foot infection requiring new antibiotic regimen.
Current anticoagulation therapy such as Warfarin, Clopidogrel and INR >2.0
Currently being treated for osteomyelitis.

Study design
Purpose of the study
Treatment
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is a proof of concept study.
Sequence quality control and analysis will be performed using CLC genomic workbench with microbial genomics module addition. Wound metrics and microbiome data will be analysed through Statistical Package for Social Sciences Version 24 (SPSS Inc., Chicago, Illinois, USA). A Wilcoxin rank sum test for non-parametric data will be used to determine the difference in Log10 before and after treatment.

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)
NSW
Recruitment hospital [1] 12512 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 24892 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 301252 0
Hospital
Name [1] 301252 0
Liverpool Hospital
Address [1] 301252 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets
LIVERPOOL NSW 2170
Country [1] 301252 0
Australia
Primary sponsor type
Government body
Name
South Western Sydney Local Health District
Address
South Western Sydney Local Health District Executive Office
Liverpool Hospital Eastern Campus
Corner of Lachlan and Hart Streets
LIVERPOOL NSW 2170
Country
Australia
Secondary sponsor category [1] 300907 0
None
Name [1] 300907 0
Address [1] 300907 0
Country [1] 300907 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301991 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 301991 0
Locked Bag 7103
Liverpool BC
NSW 1871
Ethics committee country [1] 301991 0
Australia
Date submitted for ethics approval [1] 301991 0
22/11/2018
Approval date [1] 301991 0
23/01/2019
Ethics approval number [1] 301991 0
2018/ETH00597

Summary
Brief summary
We plan to determine if, a topical wound gel (Plurogel®), commonly used in chronic wounds and burn wounds, is effective in reducing the amount of bacteria in chronic non-healing diabetic foot wounds, and what effect it may have on the rate of wound healing . By analysing the microbial wound burden prior to treatment start, we will be able to determine what effect the Plurogel has on planktonic (free floating bacteria) and wound biofilm. We will do this using real-time qPCR and 16S rRNA, to identify and quantify the bacterial to human DNA ratio. Scanning electron microscopy will be used to observe the mean amout of biofilm as a reflective marker of intervention efficacy.


The most common method to assess infection in a wound is to take a swab of the wound and see what, if any, bacteria grows. The available evidence suggests that taking a tissue sample from a suspected infected wound provides better information about what bacteria is present than taking a wound swab alone. The tissue sample is then provided to a laboratory for them to grow the bacteria. This is currently the standard way that all health care facilities operate.
In addition, we also plan to send a piece of the tissue for testing with a new advanced molecular technique, as it has recently been found that trying to grow bacteria in a laboratory may not find all the bacteria that maybe present in a wound. This could explain why some people with high levels of bacteria in their chronic wound do not respond to the standard treatments we provide such as antibiotics and/ or wound care products.
Using these new advanced methods will allow us to find all the bacteria in a wound and/or identify certain types of bacteria that don’t grow in laboratories. This may help change the way we treat infections as we can more successfully target particular bacteria, and in turn, this could potentially reduce some of the risks associated with foot infection, like amputation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88786 0
Dr Matthew Malone
Address 88786 0
High Risk Foot Service
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871
Country 88786 0
Australia
Phone 88786 0
+61 02 8738 9260
Fax 88786 0
+61 02 8738 7979
Email 88786 0
matthew.malone@health.nsw.gov.au
Contact person for public queries
Name 88787 0
Ms Saskia Schwarzer
Address 88787 0
High Risk Foot Service
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871
Country 88787 0
Australia
Phone 88787 0
+61 02 8738 8296
Fax 88787 0
+61 02 8738 7979
Email 88787 0
Saskia.Schwarzer@health.nsw.gov.au
Contact person for scientific queries
Name 88788 0
Dr Matthew Malone
Address 88788 0
High Risk Foot Service
Liverpool Hospital
Locked Bag 7103
Liverpool BC
NSW 1871
Country 88788 0
Australia
Phone 88788 0
+61 02 8738 9260
Fax 88788 0
+61 02 8738 7979
Email 88788 0
matthew.malone@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Proof of concept study only.
What supporting documents are/will be available?
No other documents available
Summary results
No Results