Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000227998
Ethics application status
Approved
Date submitted
4/02/2020
Date registered
24/02/2020
Date last updated
11/07/2022
Date data sharing statement initially provided
24/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of CUTICERIN® with or without a Regenerative Epithelial Suspension (RES™), on pigmentation of donor sites in children: The pilot randomised DRESSIng Trial
Scientific title
A pilot randomised trial evaluating the effect of CUTICERIN® with or without a Regenerative Epithelial Suspension (RES™), on pigmentation of paediatric, split-thickness skin graft donor sites: The DRESSIng Trial, a pilot randomised trial.
Secondary ID [1] 300358 0
None
Universal Trial Number (UTN)
U1111-1247-1950
Trial acronym
DRESSing Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paediatric Burns 315970 0
Condition category
Condition code
Injuries and Accidents 314248 314248 0 0
Burns

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The initial application of intervention will be under general anaesthesia by the burns surgical team using sterile technique.

ARM1:
Donor Site Intervention. The intended donor site will be marked to a maximum area of 320sqcm. Following sterile skin preparation, a donor skin biopsy will be harvested with a pneumatic dermatome(Zimmer Inc., Warsaw, IN, USA) at depth of 0.018cm(0.007in). Topical application of local aneasthesia (bupivacaine 0.25% with epinephrine 1:200,000 AstraZeneca Pty Ltd, North Ryde, NSW, Australia) , calculated at a maximum safe dose(2 to 2.5 mg/kg) will facilitate pain relief and haemostasis at the newly created donor site wound (DSW). A three step degradation process with the RECELL® Autologous Cell Harvesting (ACH) device transforms the skin biopsy in a Regenerative Epithelial Suspension (RES™) as per manufacturer specifications. The RES™ will the be applied by droplet or spray onto the donor site wound and covered with Cuticerin®, a low-adherent , impregnate dressing composed of smooth acetate fabric coated in a water repellant ointment containing petrolatum, paraffin and Eucerite®. The sequence of outer layers will be Allevyn® followed by Hypafix®. The first change of dressing will be a week post-skin graft . Thereafter Xeroform® will be applied to the DSW every 2-3 days until greater than 95% re-epithelialisation is confirmed by a burns clinician. Xeroform® is a non-adherent, petrolatum coated fine mesh gauze that contains 3% bismuth tribromophenate.

Recipient Site Intervention:
Skin graft recipient site will be marked to maximum of 400sqcm for evaluation. RES™ will then be topically applied to the recipient site followed by perforated, split-thickness skin sheet graft with or without ARTISS®, a fibrin sealant. The graft will be fixed to normal skin with or without Histoacryl® tissue glue. The sequence of secondary, outer dressings will be Mepitel® , Acticoat® , Hypafix® . Depending on the site of the skin graft negative pressure wound therapy may also be applied as per clinician assessment. Change of dressing schedule and application of Xeroform® is as described for the donor site wound.

Intervention fidelity will be assessed using a questionnaire that evaluates each step of dressing application by an investigator aligned with the study..
Intervention code [1] 316639 0
Treatment: Devices
Comparator / control treatment
ARM2:
Donor Site Intervention. The donor site wound preparation, skin graft harvest , topical haemostasis and analgesia, secondary outer dressing sequence and change of dressing schedule is same as for ARM 1. The active control will be Cuticerin® only.

Recipient Site Intervention:
Skin graft recipient site will be marked to maximum of 400sqcm for evaluation. A perforated, split-thickness skin sheet graft applied to the recipient site with or without ARTISS® . The graft may be fixed to normal skin with Histoacryl® tissue glue. The sequence of secondary, outer dressings will be Mepitel®, Acticoat®, Hypafix®. Depending on the site of the skin graft negative pressure wound therapy may also be applied as per clinician assessment. Change of dressing schedule and application of Xeroform® is as described for the donor site wound.

Intervention fidelity will be assessed using a questionnaire that evaluates each step of dressing application by an investigator aligned with the study.
Control group
Active

Outcomes
Primary outcome [1] 322633 0
Donor site pigmentation at 12 months post-split thickness skin graft: Lightness (L*)

This will be measured objectively with the DSM II ColorMeter using the CIELab colour space system and colour item of the Manchester Scar Scale(MSS). The primary approach for pigmentation will be Lightness (L*). The difference between L*(donor site) and L*(normal skin) at 12 months post skin graft will be calculated. Blinded review by panel of burns clinicians and rating of two dimensional images of donor site and contralateral normal skin (where possible) using the Manchester Scar Scale colour item.
Timepoint [1] 322633 0
Twelve months post skin graft.
Assessment of pigmentation will be made at baseline then 3, 6 and 12months post skin graft.
Secondary outcome [1] 380312 0
Donor site pigmentation at 12 months post-split thickness skin graft: Pigmentation(b*)

This will be measured objectively with the DSM II ColorMeter using the CIELab colour space system and colour item of the Manchester Scar Scale(MSS). A scondary approach for pigmentation will be pigmentation (b*). The difference between b*(donor site) and b*(normal skin) at 12 months post skin graft will be calculated. Blinded review by panel of burns clinicians and rating of two dimensional images of donor site and contralateral normal skin (where possible) using the Manchester Scar Scale colour item.
Timepoint [1] 380312 0
Twelve months post skin graft.
Assessment of pigmentation will be made at baseline then 3, 6 and 12months post skin graft.
Secondary outcome [2] 380313 0
Donor site pigmentation at 12 months post-split thickness skin graft: Melanin Index(MI)

This will be measured objectively with the DSM II ColorMeter using the Melanin Index colour space system and colour item of the Manchester Scar Scale(MSS). Another secondary approach for pigmentation will be Melanin Index (MI). The difference between MI*(donor site) and MI*(normal skin) at 12 months post skin graft will be calculated. Blinded review by panel of burns clinicians and rating of two dimensional images of donor site and contralateral normal skin (where possible) using the Manchester Scar Scale colour item.
Timepoint [2] 380313 0
Twelve months post skin graft.
Assessment of pigmentation will be made at baseline then 3, 6 and 12months post skin graft.
Secondary outcome [3] 380314 0
Donor site erythema at 12 months post-split thickness skin graft: Erythema(a*)

This will be measured objectively with the DSM II ColorMeter using the CIELab colour space system and colour item of the Manchester Scar Scale(MSS). The primary approach for erythema will be erythema (a*). The difference between a*(donor site) and a*(normal skin) at 12 months post skin graft will be calculated. Blinded review by panel of burns clinicians and rating of two dimensional images of donor site and contralateral normal skin (where possible) using the Manchester Scar Scale colour item
Timepoint [3] 380314 0
Twelve months post skin graft.
Assessment of pigmentation will be made at baseline then 3, 6 and 12months post skin graft.
Secondary outcome [4] 380317 0
Donor site pigmentation at 12 months post-split thickness skin graft: Erythema Index(EI)

This will be measured objectively with the DSM II ColorMeter using the Erythema Index colour space system and colour item of the Manchester Scar Scale(MSS). A secondary approach for erythema will be Erythema Index (EI*). The difference between EI*(donor site) and EI*(normal skin) at 12 months post skin graft will be calculated. Blinded review by panel of burns clinicians and rating of two dimensional images of donor site and contralateral normal skin (where possible) using the Manchester Scar Scale colour item.
Timepoint [4] 380317 0
Twelve months post skin graft.
Assessment of pigmentation will be made at baseline then 3, 6 and 12months post skin graft.
Secondary outcome [5] 380318 0
Donor site re-epithelialisation time.

This is defined as the number of days required for greater than or equal to 95% wound re-epithelialisation. Clinician assessment will be the primary approach. Secondary approach will be blinded two-dimensional image review by a panel of burns clinicians. Objective assessment will be by three- dimensional image assessment and this will be a secondary approach.
Timepoint [5] 380318 0
Initial assessment will be at 7 days post-graft then every 2-3 days (up to 58 weeks post skin graft) until greater than or equal to 95% wound re-epithelialisation
Secondary outcome [6] 380319 0
Donor site: Pain

The guardian will complete a proxy report of acute pain with an eleven-point, pain numeric rating scale (NRS-P Proxy, 0=no pain, 10=worst pain) will be utilised.
Timepoint [6] 380319 0
Acute pain will be assessed initially at 24 hours post skin graft then at each dressing change every 2-3 days (up to 58 weeks post skin graft) until greater than or equal to 95% wound re-epithelialisation.
Secondary outcome [7] 380320 0
Donor site: Itch

Acute itch will be assessed in the same manner as acute pain. The instrument of measurement will be an eleven-point numeric rating scale (NRS- I Proxy, 0=no itch to 10=worst itch).
Timepoint [7] 380320 0
Initial assessment will be at 7 days post-graft then every 2-3 days (up to 58 weeks post skin graft).
Secondary outcome [8] 380321 0
Donor site: Dressing application ease

A short survey of clinician opinion regarding ease, conformability, duration of dressing application and additional comments will be collected.
Timepoint [8] 380321 0
Initial dressing application will recorded at baseline and at each dressing change every 2-3 days (up to 58 weeks post skin graft) until greater than or equal to 95% wound re-epithelialisation.
Secondary outcome [9] 380322 0
Donor site: Treatment Satisfaction

An eleven-point numeric rating scale for treatment satisfaction (NRS-TS Proxy, 0=not satisfied to 10=extremely satisfied) will be taken from clinicians and guardians.
Timepoint [9] 380322 0
At greater than or equal to 95% wound re-epithelialisation and at 3, 6 and 12 months(up to 58 weeks) post skin graft.
Secondary outcome [10] 380323 0
Donor site: Scar thickness

Sonographic assessment of scar thickness will be completed with the Venue40 MSK (GE Healthcare, Fairfield, CT, USA). An average of three readings will be taken from the donor site scar.
Timepoint [10] 380323 0
At 3,6, and 12 months(up to 58 weeks) post skin graft.
Secondary outcome [11] 380324 0
Donor site: Health related quality of life - Scar Specific

This will be measured with the Brisbane Burn Scar Impact Profile (BBSIP) instrument now validated for the paediatric age group.
Timepoint [11] 380324 0
At 3,6, and 12(up to 58 weeks) months post skin graft.
Secondary outcome [12] 380325 0
Donor site: Health Related Quality of Life-Economic evaluation of interventions.

The CHU9D, a preference based ,HRQOL measure assesses worry, sadness, pain, fatigue, annoyance, school work/homework, sleep, daily routine, and ability to join in activities. The preference weights from these items are then converted to quality-adjusted life years (QALYs) for economic evaluation. This will be completed by the caregivers of all participants.
Timepoint [12] 380325 0
At 3, 6 and 12(up to 58 weeks) months post skin graft.
Secondary outcome [13] 380326 0
Donor Site: Health Resource Utilisation

For each participant, health resource utilisation will be measured including intervention related cost for each participant and health care resource use pertaining to staff labour, consumables as well as both inpatient and outpatient management where relevant.
Timepoint [13] 380326 0
At initial dressing application, at each dressing change and at 3, 6 and 12(up to 58 weeks) month post skin graft.
Secondary outcome [14] 380327 0
Reciepient site: Engraftment

Recipient site engraftment is defined as the number of days to 98% or more engraftment as assessed by the treating clinician. Primary approach will be clinician assessment. Secondary approach will be blinded review of two-dimensional, recipient site images by panel of burns clinicians. Objective assessment of engraftment will be with three-dimensional evaluation of wound area in percentage.
Timepoint [14] 380327 0
Number of days until greater than or equal to 98% recipient wound engraftment is confirmed by burns clinician.
Secondary outcome [15] 380328 0
Recipient site: Pigmentation

Recipient site pigmentation will be evaluated using the same parameters measured with the DSM II colormeter and two-dimensional image ratings with the colour item of the Manchester Scar Scale as described for the donor site. Where possible the contralateral site will be used for pigmentation assessments. This may not be applicable to large B-TBSA cases where the contralateral site is also injured. In this subset of participants, the adjacent normal skin will be utilised for assessment
Timepoint [15] 380328 0
Measurements will be taken at baseline then at 3, 6 and 12 months(up to 58 weeks) post skin graft
Secondary outcome [16] 380329 0
Recipient site: Erythema

Recipient site erythema will be evaluated using the same parameters using the DSM II colormeter, two-dimensional images and Manchester Scar Scaleand approach as described for the donor site. Where possible the contralateral site will be used for erythema assessments. This may not be applicable to large B-TBSA cases where the contralateral site is also injured. In this subset of participants, the adjacent normal skin will be utilised for assessment
Timepoint [16] 380329 0
At baseline then at 3,6, and 12 months(up to 58 weeks) post skin graft.

Eligibility
Key inclusion criteria
1. Acute burn injury requiring a split thickness skin graft for which:
a. The donor site for evaluation should not exceed 320 sqcm.
b. The split-thickness skin graft recipient site for evaluation should not exceed 400 sqcm.
2. Child (and/or accompanying guardian) is willing and able to complete all follow-up evaluations required by the study protocol.
Minimum age
No limit
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Non-English-Speaking Background
2. Child in the care of the Department of Community Services
3. Full thickness skin graft
4. Hypersensitivity to trypsin or sodium lactate.
5. Previous adverse reaction to general anaesthesia.

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 be completed with the randomisation form generated on REDCap program.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will be prepared by a statistician then uploaded onto the REDCap program by a third party individual who has no involvement in the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size is calculated based on feasibility of available participants at the study centre. A sample size of 20 patients per group (n=40) will be recruited.

Initially, descriptive statistics will be calculated for all outcomes and graphically presented. An Intention to Treat and Per Protocol approach will be used to analyse the dataset. All data except re-epithelialisation time data will be analysed using an approach appropriate for this type of longitudinal data: Mixed model regression analysis or Generalised Estimating Equations (GEE). Dependent on the distribution of the data the appropriate statistical method will be used as GEE and mixed model regression analysis give similar results when the dataset is normally distributed.

Pigmentation will be analysed using Generalised Estimating Equations(GEE). The absolute mean difference between scar and corresponding normal skin will then be calculated for each parameter (L*,b*and MI). Two-dimensional images of donor site and normal skin will classified with the colour item of the Manchester Scar Scale(MSS) as ‘perfect match’(PM), ‘slight mismatch’(SM), ‘obvious mismatch’(OM) or ‘gross mismatch’(GM). The following variables will then be entered into the statistical model: Subject Variable (Patient ID), Dependent Variable (Parameter, e.g. Lightness , L*) and Categorical Variable(Manchester Scar Scale-Colour). Scars classified as PM and SM will be deemed as acceptable outcomes. Whereas, OM and GM scars will be deemed not acceptable. Baseline co-variates( age, gender, anatomical location, Fitzpatrick Skin type, History of wound infection, wound re-epithelialisation time, burn depth and surface area burned), if significant will also be considered in the final statistical model.

The re-epithelialisation time data will be evaluated using a survival analysis model (both Kaplan Meier analysis and Cox Proportional Hazards regression), with intervention group as the explanatory variable. A ‘p’ value < 0.05 will be considered statistically significant. The two statistical software systems to be used for analysis are SPSS (IBM Corporation, Armonk, NY, USA) and Stata (StataCorp, College Station, TX, USA) where appropriate.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/07/2020
Actual
21/07/2020
Date of last participant enrolment
Anticipated
31/08/2022
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
40
Accrual to date
37
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 15682 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 29101 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 304783 0
Other Collaborative groups
Name [1] 304783 0
Innovation Connections Grant [ICG001219] by Department of Industry , Innovation and Science and Avita Medical Asia Pacific
Country [1] 304783 0
Australia
Primary sponsor type
Government body
Name
Department of Industry , Innovation and Science
Address
The Commonwealth of Australia represented by the
Department of Industry , Innovation and Science
of 10 Binara Street,
Canberra
ACT
2600
Country
Australia
Secondary sponsor category [1] 305100 0
Commercial sector/Industry
Name [1] 305100 0
Avita Medical Asia Pacific
Address [1] 305100 0
AVITA MEDICAL ASIA PACIFIC
Suite G.01, 68 South Terrace,
South Perth,
WA,
6151
Country [1] 305100 0
Australia
Secondary sponsor category [2] 305107 0
University
Name [2] 305107 0
Queensland University of Technology
Address [2] 305107 0
2 George St,
Brisbane City
QLD
4000
Country [2] 305107 0
Australia
Other collaborator category [1] 281200 0
Individual
Name [1] 281200 0
Prof Roy Kimble
Address [1] 281200 0
Queensland University of Technology Professor, Faculty of Health
Director of the Centre for Children’s Burns & Trauma Research
Service Group Director, Paediatric Surgery, Urology, Neonatal Surgery, Burns & Trauma
Clinical Lead, Paediatric Vascular Anomalies

Centre for Children's Burns and Trauma Research, Institute of Health and Biomedical Innovation(IHBI), Centre for Children's Health Research,Queensland University of Technology, 62 Graham Street, South Brisbane, QLD, 4101
Pegg Leditschke Children’s Burns Centre, Paediatric Surgery, Urology, Neonatal Surgery, Burns & Trauma,Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD, 4101
Country [1] 281200 0
Australia
Other collaborator category [2] 281201 0
Individual
Name [2] 281201 0
A/Prof Craig Anthony McBride
Address [2] 281201 0
Pegg Leditschke Children’s Burns Centre, Surgical Team for Infants, Toddlers & Children (STITCh), Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD, 4101
Centre for Children’s Burns and Trauma Research, The University of Queensland, St Lucia, QLD,4072
Menzies Health Institute, Griffith University, QLD,4222
Country [2] 281201 0
Australia
Other collaborator category [3] 281202 0
Individual
Name [3] 281202 0
Dr Bhaveshkumar Patel
Address [3] 281202 0
Pegg Leditschke Children’s Burns Centre, Surgical Team for Infants, Toddlers & Children (STITCh), Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD, 4101
Centre for Children’s Burns and Trauma Research, The University of Queensland, St Lucia, QLD, 4072
Country [3] 281202 0
Australia
Other collaborator category [4] 281203 0
Individual
Name [4] 281203 0
Dr Zephanie Tyack
Address [4] 281203 0
Centre for Children's Burns and Trauma Research,The University of Queensland, Centre for Children's Health Research, 62 Graham Street, South Brisbane, QLD, 4101
Country [4] 281203 0
Australia
Other collaborator category [5] 281204 0
Individual
Name [5] 281204 0
Prof Steven M. McPhail
Address [5] 281204 0
Australian Centre for Health Services Innovation(AusHSI),School of Public Health and Social Work, Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia, 4001
Centre for Functioning and Health Research, Brisbane, QLD, Australia,4102
Country [5] 281204 0
Australia
Other collaborator category [6] 281205 0
Individual
Name [6] 281205 0
Dr Anjana Bairagi
Address [6] 281205 0
Centre for Children's Burns and Trauma Research, Institute of Health and Biomedical Innovation(IHBI), Centre for Children's Health Research,Queensland University of Technology, 62 Graham Street, South Brisbane, QLD, 4101
Pegg Leditschke Children’s Burn Centre, Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD, 4101
Country [6] 281205 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305197 0
CHILDREN’S HEALTH QUEENSLAND HOSPITAL AND HEALTH SERVICE HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 305197 0
Ethics committee country [1] 305197 0
Australia
Date submitted for ethics approval [1] 305197 0
03/09/2018
Approval date [1] 305197 0
11/02/2019
Ethics approval number [1] 305197 0
HREC/18/QCHQ/45807
Ethics committee name [2] 305203 0
University Human Research Ethics Committee (UHREC)
Ethics committee address [2] 305203 0
Ethics committee country [2] 305203 0
Australia
Date submitted for ethics approval [2] 305203 0
21/11/2019
Approval date [2] 305203 0
06/12/2019
Ethics approval number [2] 305203 0
1900001073

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99574 0
A/Prof Bronwyn Griffin
Address 99574 0
Senior Research Fellow, National Health and Medical Research Council Centre of Research Excellence in Wiser Wound Care Menzies Health Institute Queensland, Griffith University, Nathan campus , Queensland, 4111.

Senior Clinical Research Fellow, QUT Honorary Senior Fellow, UQ Centre for Children's Burns and Trauma Research, QUT Queensland Children's Hospital, South Brisbane, Queensland, 4101
Country 99574 0
Australia
Phone 99574 0
+61730697392
Fax 99574 0
Email 99574 0
[email protected]
Contact person for public queries
Name 99575 0
Anjana Bairagi
Address 99575 0
Queensland University of Technology, Centre for Children's Burns and Trauma Research, Centre for Children's Health Research, 62 Graham Street, South Brisbane, QLD, 4101 Pegg Leditschke Children’s Burn Centre, Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD, 4101
Country 99575 0
Australia
Phone 99575 0
+61730697436
Fax 99575 0
Email 99575 0
[email protected]
Contact person for scientific queries
Name 99576 0
Anjana Bairagi
Address 99576 0
Queensland University of Technology, Centre for Children's Burns and Trauma Research, Centre for Children's Health Research, 62 Graham Street, South Brisbane, QLD, 4101 Pegg Leditschke Children’s Burn Centre, Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD, 4101
Country 99576 0
Australia
Phone 99576 0
+61730697436
Fax 99576 0
Email 99576 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
Sensitive nature of IPD


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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