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Trial registered on ANZCTR


Registration number
ACTRN12623000154606
Ethics application status
Approved
Date submitted
6/02/2023
Date registered
16/02/2023
Date last updated
16/02/2023
Date data sharing statement initially provided
16/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of topical Benzalkonium chloride (BAC) wound gel on chronic infections in Diabetes Related Foot Ulcers (DRFUs): An in vivo proof of concept study
Scientific title
The effects of topical Benzalkonium chloride (BAC) wound gel on microbial loads in chronic infections in Diabetes Related Foot Ulcers (DRFUs): An in vivo proof of concept study
Secondary ID [1] 308447 0
nil known
Universal Trial Number (UTN)
U1111-1285-0440
Trial acronym
BLASTX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
diabetes 328247 0
diabetic foot ulcer 328248 0
chronic wound 328249 0
Condition category
Condition code
Metabolic and Endocrine 325295 325295 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We propose to undertake an in vivo pilot study in 20 diabetes related foot ulcers (DRFUs) complicated by chronic infections to identify the effects of a benzalkonium chloride-containing wound gel (BLASTX™). We will assess the total microbial load before, during and after therapy through quantitative polymerase chain reaction (qPCR) to estimate the number of bacteria. We will also use a combination of molecular and microscopy techniques (16S rDNA sequencing, Scanning electron microscopy [SEM], and peptide nucleic acid fluorescent in situ hybridisation [PNA-FISH]) to better understand the effects of the wound gel on in vivo biofilms and the microbiome.

For the total duration of 12 weeks, the BAC wound gel will be applied to the ulcer every second day as the primary dressing. The total amount utilised will depend on the size of the wound, but application should cover the majority of the wound surface. A non-adhesive, adsorbent pad, such as a foam, will be used as a secondary dressing and secured to the foot with and adhesive, non-woven fabric tape. Participants may be asked to change their own dressings between follow ups or may have community nurses change their dressings in keeping with a normal dressing regime as per standard of care. The use of BAC wound gel does not constitute any additional dressing changes or visits to that of standard of care (SOC).

SOC will be undertaken by a podiatrist, medical team and/or member of the research team. It involves performing appropriate wound bed preparation through conservative sharps debridement or curettage, wound cleansing with sodium chloride 0.9% and the replacement of a non-adherent, absorbent wound dressing. SOC may also involve offloading of plantar diabetes-related foot ulcers with a removable cast boot (DH Offloading Walker, Össur Australia) and for non-plantar DRFUs, a post-op shoe (Darco all-purpose boot, Össur Australia).

Participants will be required to attend one thirty-minute appointment per week for the duration of the study (12 weeks or until healing is achieved). This is in keeping with the frequency of dressing changes and requirement for follow up as per SOC.

At the initial, baseline appointment (week 0), participants will attend the Liverpool Hospital High Risk Foot Service and will be assessed as suitable (from the inclusion criteria) by the research podiatrist. If the individual consents to participation, a full wound history (including aetiology and lower limb vascular supply) and medical history (relevant demographic and medical data) will be recorded, a wound review (wound size, location, Wound, Ischaemia, foot Infection [WIfI] score) and wound photography will occur, as well as a wound swab and tissue curettage. Wound review and wound swab will be repeated at weeks 3, 6, 9 and 12 (end of study) or when healing is achieved (end of study) by the research podiatrist. An additional tissue curettage will occur at week 12 (end of study) by the research podiatrist if the wound is deemed suitable for this.

Participants progress and adherence to the study will be followed closely by the research podiatrist through calendar scheduling and memos as well as a session attendance checklist. After this period, all participants may continue to be followed in the Liverpool Hospital High-Risk Foot Clinic by podiatry staff as part of their routine care especially if wound healing has not occurred.
Intervention code [1] 324894 0
Treatment: Other
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333756 0
Change in total microbial loads of diabetes-related foot ulcers after the use of benzalkonium chloride (BAC) wound gel, assessed using qPCR to estimate microbial loads (expressed as Log10 16S Copies).
Timepoint [1] 333756 0
Baseline (week 0), weeks 3, 6, 9 and 12 post-commencement of second-daily application of BAC and SOC in keeping with ulcer requirements.
Secondary outcome [1] 418191 0
This is a composite secondary outcome:
1. Examine the change in microbial composition and diversity of diabetes-related foot ulcers before using BAC wound gel and SOC.
2. Examine the change in microbial composition and diversity of diabetes-related foot ulcers after using BAC wound gel and SOC at weeks 3, 6, 9 and 12 post-commencement of this.
This will be done using 16S rDNA sequencing.
Timepoint [1] 418191 0
Baseline (week 0), weeks 3, 6, 9 and 12 post-commencement of second-daily application of BAC and SOC in keeping with ulcer requirements.
Secondary outcome [2] 418194 0
This is a composite secondary outcome:
To determine if biofilms are present in diabetes-related foot ulcers using:
1. Scanning electron microscopy to visualize biofilm structures and;
2. PNA-FISH to assess spatial organization.
Timepoint [2] 418194 0
Baseline (week 0), weeks 3, 6, 9 and 12 post-commencement of second-daily application of BAC and SOC in keeping with ulcer requirements.
Secondary outcome [3] 418195 0
The percentage of wounds healed at 12 weeks, assessed by the research podiatrist and/or research team at weekly follow up/ review.
Timepoint [3] 418195 0
12 weeks post-commencement of second-daily application of BAC and SOC.
Secondary outcome [4] 418196 0
Change in wound metric data over the duration of the study as assessed by the research podiatrist and/or research team objectively by an audit of clinical records throughout the duration of the study.
Timepoint [4] 418196 0
Baseline (week 0), weeks 3, 6, 9 and 12 post-commencement of second-daily application of BAC and SOC in keeping with ulcer requirements.

Eligibility
Key inclusion criteria
1. Diagnosis of either 1 or type 2 diabetes mellitus
2. Aged over 18 years
3. Diabetes-related foot ulcer occurring below the malleolus stratified by; DRFU with a suspicion of chronic infection with foot ulcers greater than or equal to 5 week’s duration with no observed changes in wound metrics over a lead-in period of four consecutive weeks prior to enrolment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Malignant ulcers
2. Ulcers associated with chemotherapy
3. Venous ulceration
4. Thermal injuries (burns)
5. Current uncontrolled anticoagulation therapy such as warfarin, clopidogrel and International Normalised Ratio (INR) >2.0
6. New acute diabetes related foot infection requiring new antibiotic regimen
7. 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)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This is a longitudinal prospective proof of concept study to explore the effectiveness of Standard of Care (SOC) plus application of BAC in 20 patients with diabetes-related foot ulcers and chronic infection.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
In this longitudinal proof-of-concept study, we plan to enrol 20 individuals presenting to the Liverpool Hospital High Risk Foot Service (Sydney, Australia) with a diabetes-related foot ulcers suspected of having a local chronic biofilm infection. We believed 20 individual diabetes-related foot ulcers is sufficient to form some proof of concept for a wound dressing's ability to impact biofilm and may be the first pivotal stage in building an evidence base for their continued use.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2023
Actual
Date of last participant enrolment
Anticipated
1/03/2024
Actual
Date of last data collection
Anticipated
1/06/2024
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23915 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 39406 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 312692 0
Commercial sector/Industry
Name [1] 312692 0
Next Science®
Country [1] 312692 0
Australia
Primary sponsor type
Government body
Name
South Western Sydney Local Health District
Address
Liverpool Hospital
Corner Elizabeth and Goulburn Streets, Liverpool NSW 2170
Country
Australia
Secondary sponsor category [1] 314305 0
Commercial sector/Industry
Name [1] 314305 0
Next Science®
Address [1] 314305 0
Level 19, Tower A, The Zenith
821 Pacific Highway, Chatswood
NSW 2067
Country [1] 314305 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311993 0
South Western Sydney Local Health District Ethics Committee
Ethics committee address [1] 311993 0
Research and Ethics Office
Locked Bag 7103
Liverpool BC NSW 1871
Australia
Ethics committee country [1] 311993 0
Australia
Date submitted for ethics approval [1] 311993 0
14/11/2022
Approval date [1] 311993 0
18/01/2023
Ethics approval number [1] 311993 0
2022/ETH02421

Summary
Brief summary
This is a longitudinal proof-of-concept study of benzalkonium chloride (BAC) wound gel in conjunction with standard of care (SOC), We plan to enroll 20 individuals presenting to the Liverpool Hospital High Risk Foot Service (Sydney, Australia) with a diabetes-related foot ulcer (DRFU) suspected of having a local chronic biofilm infection. "Biofilm" is a term given to microorganisms, typically bacteria, that demonstrate alterations in behaviour, such as slow growth, multi-drug resistance, virulence, pathogenicity and aggregation. They are not visible to the naked eye and hence clinicians cannot see which tissue to target during sharps debridement, therefore debridement alone may not be enough to remove biofilms.

This study has been designed to provide proof of concept regarding a wound dressing's ability to impact biofilm and may assist in building an evidence base for their continued use in wounds with chronic biofilm infection.

We plan to assess the total microbial microbial load before, during and after therapy. We will use a combination of molecular and microscopy techniques to determine the number of bacteria and to better understand the effects of the wound gel on biofilms in real study participants, living with a DRFU with chronic biofilm infection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123098 0
Miss Saskia Schwarzer
Address 123098 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets
LIVERPOOL NSW 2170
Country 123098 0
Australia
Phone 123098 0
+61 287388296
Fax 123098 0
+61 287388297
Email 123098 0
Saskia.Schwarzer@health.nsw.gov.au
Contact person for public queries
Name 123099 0
Miss Saskia Schwarzer
Address 123099 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets
LIVERPOOL NSW 2170
Country 123099 0
Australia
Phone 123099 0
+61 287388296
Fax 123099 0
+61 287388297
Email 123099 0
Saskia.Schwarzer@health.nsw.gov.au
Contact person for scientific queries
Name 123100 0
Miss Saskia Schwarzer
Address 123100 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets
LIVERPOOL NSW 2170
Country 123100 0
Australia
Phone 123100 0
+61 287388296
Fax 123100 0
+61 287388297
Email 123100 0
Saskia.Schwarzer@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
Individual data is not necessarily reflective of the overall outcome, and is confidential and sensitive.


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.