Trial Review

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
ACTRN12617001632381
Ethics application status
Approved
Date submitted
27/11/2017
Date registered
15/12/2017
Date last updated
20/11/2019
Date data sharing statement initially provided
20/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An adaptive clinical trial of topical, anti-inflammatory dressings on pain in adults
with venous leg ulcers: Pilot study
Scientific title
An adaptive clinical trial of topical anti-inflammatory agents on pain in patients with venous leg ulcers: A Sequential Multiple Assignment Randomised Trial - Pilot study
Secondary ID [1] 293465 0
None
Universal Trial Number (UTN)
U1111-1205-7928
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
venous leg ulcers 305655 0
pain 305656 0
Condition category
Condition code
Cardiovascular 304875 304875 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This Sequential Multiple Assignment Randomised Trial design will assess the effectiveness of an ibuprofen foam wound dressing plus standard care; and an activated carbon dressing (2nd intervention for non-responders to first intervention) in participants with venous leg ulcers. This design is an adaptive intervention approach.
The dressings will be administered once/week for 4 weeks during normal wound dressing change appointments by the patient's routine clinician in charge of care.
As the dressings will be applied underneath compression therapy (standard care for venous leg ulcers), which should remain in place for a week, the return of the patient with the dressing and compression therapy still in place will indicate adherence to the intervention.
This pilot study will have a four-week treatment assessment period including two stages. In Stage 1, intervention patients will receive an ibuprofen-impregnated foam dressing (Biatain® Ibu) plus standard care. The dressings are manufactured by Coloplast, who produce a foam dressing with the addition of 0.5 mg/cm2 of ibuprofen dispersed throughout the foam, Biatain® Ibu. In Stage 2, participants who do not respond to the ibuprofen dressing (i.e. do not achieve = a decrease of 3 on the NRS for pain), will commence a one week wash-out phase with a non-medicated foam dressings, then start treatment with an activated carbon cloth dressing (Zorflex®) plus standard care.
Standard care is defined as comprehensive assessment, a non-adherent wound dressing (no specific dressing is recommended), and graduated compression therapy, as per the Australian evidence-based guidelines for venous leg ulcers (AWMA & NZWCS, Cambridge Publishing, 2011).
Intervention code [1] 299706 0
Treatment: Devices
Intervention code [2] 299790 0
Treatment: Drugs
Comparator / control treatment
The control group will receive a non-medicated foam dressing (Biatain®) plus standard care. The dressings will be administered once/week for 4 weeks during normal wound dressing change appointments by the patient's routine clinician in charge of care.
As the dressings will be applied underneath compression therapy (standard care for venous leg ulcers), which should remain in place for a week, the return of the patient with the dressing and compression therapy still in place will indicate adherence to the intervention.
Standard care is defined as comprehensive assessment, a non-adherent wound dressing (no specific dressing is recommended), and graduated compression therapy, as per the Australian evidence-based guidelines for venous leg ulcers (AWMA & NZWCS, Cambridge Publishing, 2011).
Control group
Active

Outcomes
Primary outcome [1] 304066 0
Pain, as measured on a Pain Numerical Rating Scale 0-10
Timepoint [1] 304066 0
one week and four weeks from enrolment in study
Secondary outcome [1] 340833 0
Percent change in ulcer area. Ulcer area will be measured by using an acetate tracing of the wound, then area calculated using a digital planimetry (Visitrak) device, and a second calculation undertaken using a software measuring program, ImageJ. Ulcer area will be traced at baseline and weekly for 4 weeks.
Timepoint [1] 340833 0
weekly for four weeks from enrolment
Secondary outcome [2] 341101 0
adverse events, e.g. possible adverse events may include local irritation or stinging sensation. Participants will be asked every week whether any adverse events have occurred re their health, both related or unrelated to the ulcer treatment.
Timepoint [2] 341101 0
at every visit, i.e. weekly for 4 weeks

Eligibility
Key inclusion criteria
• patients with leg ulcers of primarily venous aetiology present for at least 4 weeks
• Ankle Brachial Pressure Index equal to or more than 0.8, and < 1.3.
• ulcer size at least 2cm2 , with exudate present
• able to understand to give consent
• patients report a pain score of at least 3 on a Numerical Rating Scale of 0 – 10
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients with a leg ulcer of non-venous aetiology (e.g. arterial, diabetic, malignancy, or other causes).
• Patients with clinical signs of wound infection
• Patients prescribed oral NSAIDs
• Patients with contradictions for NSAID use (i.e. renal disease, gastrointestinal bleeding, clotting disorders, and asthma)
• Patients with cognitive impairment

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)
Allocation Concealment will involve an administration assistant preparing sealed opaque envelopes with sequential study participant randomisation numbers on the outside and the group allocation inside the sealed envelope for each participating wound clinic. Upon recruitment of a participant, the research assistant will contact the central (off-site) project coordinator to obtain the randomized group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A random allocation sequence will be generated by an administrative assistant prior to commencement of recruitment using a computer generated randomization program ‘Research Randomizer’ https://www.randomizer.org
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
This study will have a Sequential Multiple Assignment Randomised Trial design to assess the effectiveness of ibuprofen foam wound dressing plus standard care, compared to a non-medicated foam dressing plus standard care; and an activated carbon dressing (for non-responders) on pain in participants with chronic venous leg ulcers. This design is an adaptive intervention approach which mirrors the clinical decision making process when individualising treatment, allowing treatments to be adapted over time according to the individual’s response to initial treatment. In this study, the first step will be a randomised trial of the ibuprofen foam dressing, compared to a non-medicated foam dressing. After a week, the second step will be allocation of ‘non-responders’, i.e. those who fail to report a significant clinical reduction in pain (i.e. a decrease of 3 or more on a Numerical Rating Scale 0–10), to an activated carbon dressing.
Thus the study will have a four-week treatment assessment period including two stages. In Stage 1, patients will be randomised to either a non-medicated foam dressing (Biatain®) plus standard evidence-based care; or an ibuprofen-impregnated foam dressing (Biatain® Ibu) plus standard care. The dressings are manufactured by Coloplast, who produce both an unmedicated foam dressing, Biatain®, and a foam dressing with the addition of 0.5 mg/cm2 of ibuprofen dispersed throughout the foam, Biatain® Ibu. In Stage 2, participants who do not respond to the ibuprofen dressing (i.e. do not achieve a decrease of 3 or more on the NRS for pain), will commence a one week wash-out phase with a non-medicated foam dressings, then start treatment with an activated carbon dressing.
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Separate analyses will be conducted on patients who are responsive at week 1 and those who are non-responsive at week 1.
Frequency distributions and histograms of all variables will be run to check for invalid, missing and inconsistent values. Analysis of responders will compare patients on non-medicated foam dressing with those on IBU+ treatment. Analysis of non-responders will compare patients on a carbon dressing with those on IBU+ treatment. Analysis will be conducted on the primary outcome of self-reported pain measured on a NRS; using one-way using analysis of variance, subject to fulfilment of standard assumptions; or non-parametric techniques if needed. Where necessary, post hoc testing using an appropriate procedure will be utilised.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/01/2018
Actual
30/08/2018
Date of last participant enrolment
Anticipated
10/12/2019
Actual
Date of last data collection
Anticipated
7/01/2020
Actual
Sample size
Target
30
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9449 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 9509 0
Holy Spirit Northside - Chermside
Recruitment postcode(s) [1] 18175 0
4029 - Herston
Recruitment postcode(s) [2] 18251 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 298089 0
University
Name [1] 298089 0
Queensland University of Technology
Country [1] 298089 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
Victoria Park Road
Kelvin Grove, Qld, 4059
Country
Australia
Secondary sponsor category [1] 297166 0
None
Name [1] 297166 0
Address [1] 297166 0
Country [1] 297166 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299110 0
Royal Brisbane & Women's Hospital HREC
Ethics committee address [1] 299110 0
Royal Brisbane & Women's Hospital
Level 7 Block 7
Butterfield St
Herston, Qld, 4029
Ethics committee country [1] 299110 0
Australia
Date submitted for ethics approval [1] 299110 0
25/09/2017
Approval date [1] 299110 0
21/11/2017
Ethics approval number [1] 299110 0
HREC/17/QRBW/556
Ethics committee name [2] 304776 0
St Vincent's Health and Aged Care Human Research and Ethics Committee
Ethics committee address [2] 304776 0
Holy Spirit Northside Private Hospital,
627 Rode Rd,
Chermside, Qld, 4032
Ethics committee country [2] 304776 0
Australia
Date submitted for ethics approval [2] 304776 0
06/11/2017
Approval date [2] 304776 0
28/03/2018
Ethics approval number [2] 304776 0
17/42
Ethics committee name [3] 304777 0
Queensland University of Technology Human Research Ethics Committee
Ethics committee address [3] 304777 0
88 Musk Avenue,
Kelvin Grove, Qld, 4059
Ethics committee country [3] 304777 0
Australia
Date submitted for ethics approval [3] 304777 0
03/11/2017
Approval date [3] 304777 0
30/11/2017
Ethics approval number [3] 304777 0
1700001108

Summary
Brief summary
SYNOPSIS
Study Title: An adaptive trial of topical anti-inflammatory agents on pain in patients with chronic venous leg ulcers: A Sequential Multiple Assignment Randomised Trial - Pilot study
Development Phase: IV, Pilot Study
Purpose: The primary purpose of this study is to evaluate the effectiveness of an anti-inflammatory wound dressing, containing ibuprofen, on pain levels of patients with chronic venous leg ulcers. The primary hypothesis is that this ibuprofen-impregnated wound dressing will result in reduced levels of pain, in comparison to a non-medicated dressing.
Indication: Pain score of 3 or more on the Numerical Rating Scale (0-10) in patients with venous leg ulcers
Study Therapy: Group 1- Ibuprofen impregnated foam dressing, compared to a non-medicated foam dressing.
Group 2 – Activated Carbon dressing. A pragmatic adaptive multiple allocation trial design will evaluate an antimicrobial and anti-inflammatory activated carbon dressing for participants who fail to respond, i.e. whose pain scores do note reduce by 3 or more on a 0-10 rating scale; to the ibuprofen dressing.

Study Population: Male and female adults with chronic venous leg ulcers (present for 4 weeks or more) and who fit with the study inclusion/exclusion criteria will be recruited into the study.
For this pilot study, 30 study participants will be recruited.

No. Centres: Queensland University of Technology; Royal Brisbane & Women’s Hospital; Holy Spirit Northside Private Hospital

Study Design: The study has a Sequential Multiple Assignment Randomised Trial design.

Study Duration: Total of 4 weeks

Objectives of the Study: This pilot study aims to obtain preliminary evidence on the effectiveness of two anti-inflammatory wound dressings on pain in patients with chronic venous leg ulcers. A sequential, multiple allocation randomised controlled trial of an ibuprofen-impregnated foam dressing, or an activated carbon dressing for non-responders, will be compared with a non-medicated foam dressing.

Study Endpoints:
(Primary and Secondary) The primary outcomes of this pilot Sequential Multiple Assignment Randomised Trial is to obtain preliminary evidence on the effectiveness of two anti-inflammatory wound dressings on pain in patients with chronic venous leg ulcers.
Secondary outcomes include obtaining evidence on the feasibility of the study and variation in outcome measures, to guide future applications for a fully powered trial.
The primary safety endpoints will be incidence of treatment emergent adverse events with study participants assessed prior to commencing the trial and then again following every week for adverse effects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79322 0
Dr Kathleen Finlayson
Address 79322 0
Institute of Health and Biomedical Innovation,
Queensland University of Technology
60 Musk Avenue
Kelvin Grove, Qld, 4059
Country 79322 0
Australia
Phone 79322 0
61 7 31386105
Fax 79322 0
61 7 31386030
Email 79322 0
[email protected]
Contact person for public queries
Name 79323 0
Dr Kathleen Finlayson
Address 79323 0
Institute of Health and Biomedical Innovation,
Queensland University of Technology
60 Musk Avenue
Kelvin Grove, Qld, 4059
Country 79323 0
Australia
Phone 79323 0
61 7 31386105
Fax 79323 0
Email 79323 0
[email protected]
Contact person for scientific queries
Name 79324 0
Dr Kathleen Finlayson
Address 79324 0
Institute of Health and Biomedical Innovation,
Queensland University of Technology
60 Musk Avenue
Kelvin Grove, Qld, 4059
Country 79324 0
Australia
Phone 79324 0
61 7 31386105
Fax 79324 0
Email 79324 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
As yet approval has not been applied for


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
3836Basic resultsNo 374066-(Uploaded-08-02-2021-14-15-51)-Basic results summary.pdf

Documents added automatically
No additional documents have been identified.