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Trial registered on ANZCTR


Registration number
ACTRN12618000245291
Ethics application status
Approved
Date submitted
1/02/2018
Date registered
15/02/2018
Date last updated
6/08/2019
Date data sharing statement initially provided
6/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Autologous skin cell suspension in partial thickness paediatric burns: The BRACS Randomised Trial.
Scientific title
The Biobrane®, RECELL® Autologous Cell Suspension and Silver Dressings Trial (BRACS Trial): A three arm prospective randomised controlled trial comparing a biological dressing (Biobrane®) with Biobrane® and RECELL® and with standard silver dressings in children with a superficial partial to mid dermal thickness burn
Secondary ID [1] 293743 0
nil known
Universal Trial Number (UTN)
nil known
Trial acronym
BRACS Trial: Biobrane®, RECELL® Autologous Cell suspension and Silver dressings trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paediatric Burns 306119 0
Condition category
Condition code
Injuries and Accidents 305239 305239 0 0
Burns

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The initial dressing application will be conducted under a general anaesthetic within 48 hours of the burn injury. All participants will undergo a non-excisional debridement and cleaning with QV Wash prior to dressing application.

ARM 1: one of the two standard initial dressings Acticoat® (Smith and Nephew, Hull, UK) with Mepitel® (Molnlycke, Goteborg, Sweden) or Mepilex Ag® (Molnlycke, Goteborg, Sweden) will be applied. The second dressing change will occur 3-5 days after this. Each dressing change will be as per the standard procedure with research assessments at each dressing change until the wound is 95% or more re-epithelialised or referred for a graft.

ARM 2: Once the wound bed is sufficiently prepared the surgeon will apply the autologous cell suspension using the RECELL® Autologous Cell Harvesting Device (AVITA Medical, California, USA) as per the manufacturer’s recommendations. A layer of Biobrane® (Smith & Nephew Medical Ltd, Hull, UK) will be laid over the top of the RECELL® and the edges will be secured with Hypafix® (BSN Medical GmBH, Hamburg, Germany). Over the top of the Biobrane® will be a layer of Jelonet® (Smith & Nephew Medical Ltd, Hull, UK) then Kerlix® (Covidien, Mansfield, Ma, USA), and crepe bandage; secured by Hypafix®. The Jelonet®, Kerlix®, Crepe and external Hypafix® will be changed every 3-5 days until the wound is 95% or more re-epithelialised or Biobrane® is completely detached from the neo-epithelium.

DONOR SITE: The donor site location will be selected in a proximity as close as possible to the burn wound. The preparation of the site will undergo antimicrobial washing and irrigation. Once sufficient preparation has been achieved a pneumatic dermatome (Zimmer Inc., Warsaw, IN, USA) will be used to harvest a skin donor at a thickness of 6/1000 of an inch. Any excess autologous skin cell suspension will be applied to the donor site and dressed with inert standard dressing as per surgeon preference.

ARM 3: Once the wound bed is sufficiently prepared the surgeon will apply a layer of Biobrane® over the burn, which will be secured with Hypafix®. Over the top of the Biobrane® will be a layer of Jelonet® then Kerlix®, Crepe bandage; secured by Hypafix®. The Jelonet®, Kerlix®, crepe bandage and external Hypafix® will be changed every 3-5 days until the wound is 95% or more re-epithelialised or Biobrane® is completely lifted. Most of dressing changes will be completed by our burns nursing staff and where required a surgeon will also assist with the dressing changes.
Intervention code [1] 299997 0
Treatment: Devices
Comparator / control treatment
This study will implement active group controls( Arm 1: Standard Silver Dressings) as it would be unethical to implement an inferior dressing as a control.
Control group
Active

Outcomes
Primary outcome [1] 304394 0
Days to Re-epithelialisation
Days to Re-epithelialisation of burn will be assessed with the implentation of three methods:
1. Clinical judgement from the consultant;
2. 3D camera photographs and analysis on specialist computer software; and
3. Blinded review of the 3D photographs by a panel of burn specialists (consultants and nurses). The 3D images will be obtained using a static 3D LifeVizII System® (Quantificare S.A., Cedex, France) and analysed with the Dermapix® (Quantificare S.A., Cedex, France) software. A dynamic 3D image will be taken with the GPC 3D Woundcare ( GPC, Swansea, UK) system. The clinical judgement of the attending burns surgeon will be the main assessment modality.

Timepoint [1] 304394 0
Days to Re-epithelialisation:
The number of days from date of burn injury to 95% or more wound re-epithelialisation or date of skin graft as determined by the attending burns surgeon.
Secondary outcome [1] 341809 0
Pain:
Pain will be assessed using Faces Pain Scale-Revised by participants older than 5 years); Numeric Rating Scale-Pain (NRS-P Proxy by all patients and NRS-P by participants older than 8-years) and the Faces, Legs, Activity Cry, Consolability (FLACC by nursing staff).
Timepoint [1] 341809 0
At initial dressing application and each dressing change (before and after dressing removal then before and after dressing application) until 95% or more wound re-epithelialisation as determined by the attending burns surgeon.
Secondary outcome [2] 341814 0
Ease of Dressing Application:
Dressing application ease will be assessed using a survey regarding the interventions by the burns clinicians.
Timepoint [2] 341814 0
After each dressing change until 95% or more wound re-epithelialisation as determined by the attending burns surgeon.
Secondary outcome [3] 341820 0
Burn Depth:
Burn Depth will be assessed using a Moor LDLS-BI Laser Doppler Imager® (Moor Instruments Ltd, Axminster, Devon, UK) by measuring blood perfusion at the burn site.
Timepoint [3] 341820 0
At initial dressing application and each dressing change until 95% or more wound re-epithelialisation as determined by the attending burns surgeon.
Secondary outcome [4] 341822 0
Itch intensity:
Acute Itch intensity will be self-reported for children aged 8 years and older using an 11-point Numeric Rating Scale (NRS- I) and by parents (NRS- I Proxy) of all children until the wound is 95% or more re-epithelialised. Chronic itch intensity will be measured using the itch items of the Patient and Observer Scar Assessment Scale (POSAS) and (Brisbane Burn Scar Impact Profile) BBSIP instruments.
Timepoint [4] 341822 0
Acute Itch: at all change of dressing until the wound is 95% or more re-epithelialized as determined by the attending burns surgeon.
Chronic Itch: at the 3, 6, and 12 months post date of burn injury follow up visit
Secondary outcome [5] 341823 0
Adverse Event/Discontinuation:
Minimal adverse events are expected from the proposed interventions. At the study centre, known potential adverse events (e.g. infection, haematoma, intensive care admissions) have a standardised management protocol. Adverse events related to the interventions will be monitored through review of patient medical records, by guardian and participant (where applicable) self-report and by the treating clinicians. All adverse events will be communicated to the clinical health service and Human Research Ethics Committee (HREC). Discontinuation or alteration of treatment will be at the discretion of the treating clinical team. An independent Safety Monitoring Group will also monitor all aspects of patient safety throughout the study on a regular basis. After a minimum of 30 participants have been recruited,an independent statistician (blinded to the treatment allocation) will complete an interim analysis.
Timepoint [5] 341823 0
Through the study at any specific time.
Last possible assessment will be at 12 months post date of burn injury.
Secondary outcome [6] 342974 0
Scar Assessment: Scar thickness.
Scar thickness will be measured using the Venue40 (GE Healthcare, Fairfield, CT, USA). ultrasound machine. An average of three measurements will be recorded and used in the analysis.
Timepoint [6] 342974 0
This measurements will be taken at 3 ,6 and 12 months post date of burn injury.
Secondary outcome [7] 342976 0
Scar Assessment: Subjective Severity.
Subjective scar severity will be evaluated using the Patient and Observer Scar Assessment Scale (POSAS) by a burns clinician, caregivers of all participants and by the self-report of participants aged 8 years and over.
Timepoint [7] 342976 0
This measurements will be taken at 3 ,6 and 12 months post date of burn injury.
Secondary outcome [8] 342977 0
Scar Assessment: Pigmentation(b*).
Scar Pigment will be measured using the DSMII ColorMeter® (Cortex Technology, Hadsund, Denmark). The mean of three measurements of both the scar and healthy skin will be taken


Timepoint [8] 342977 0
Measurement will be taken at each of the 3, 6 and 12 month post date of burn injury follow up visits.
Secondary outcome [9] 342978 0
Scar Assessment: Erythema (a*).
Scar Erythema will be measured using the DSMII ColorMeter® (Cortex Technology, Hadsund, Denmark). The mean of three measurements of both the scar and healthy skin will be taken. This will be the primary approach for scar vascularity.
Timepoint [9] 342978 0
Measurement will be taken at each of the 3, 6 and 12 month post date of burn injury follow up visits.
Secondary outcome [10] 342979 0
Scar Assessment: Lightness (L*).
Scar Lightness will be measured using the DSMII ColorMeter® (Cortex Technology, Hadsund, Denmark). The mean of three measurements of both the scar and healthy skin will be taken. This will be the primary approach for the outcome of scar colour.
Timepoint [10] 342979 0
Measurement will be taken at each of the 3, 6 and 12 month post date of burn injury follow up visits.
Secondary outcome [11] 342981 0
Health Related Quality of Life: Economic evaluation of interventions.
The CHU-9D is a preference based utility measure that will assess worry, sadness, pain, fatigue, annoyance, school work/homework, sleep, daily routine, and ability to join in activities. The preference weights from these are then converted to quality-adjusted life years (QALYs) for economic evaluation. This will be completed by the caregivers of all participants.
Timepoint [11] 342981 0
Measurement will be taken at each of the 3, 6 and 12 month post date of burn injury follow up visits.
Secondary outcome [12] 342982 0
Health-related Quality of Life: specific to burn scars.
The BBSIP will be used to measure the intensity and frequency of sensations, such as pain, tightness and discomfort as well as health-related quality of life specific to people with burn scars. This will be completed by the by the parent/guardian for all participants.
Timepoint [12] 342982 0
Measurement will be taken at each of the 3, 6 and 12 month post date of burn injury follow up visits.
Secondary outcome [13] 342983 0
Treatment Satisfaction:
Parent/guardian treatment satisfaction will be measured using an 11-point Numeric Rating Scales ( NRS- TS, 0= not at all satisfied to 10 = extremely satisfied).
Timepoint [13] 342983 0
At 95% or more re-epithelialisation and at 12 months post date of burn injury outpatient review.
Secondary outcome [14] 342984 0
Treatment Satisfaction:
Clincian treatment satisfaction will be measured using an 11-point Numeric Rating Scales ( NRS- TS, 0= not at all satisfied to 10 = extremely satisfied).
Timepoint [14] 342984 0
At 95% or more re-epithelialisation and on last review at 12 months post date of burn injury.
Secondary outcome [15] 342988 0
Health Resource Utilisation:
Resource utilisation will be recorded for each participant from the perspective of the health service. This will include trial-intervention-related resource use for participants in each trial arm, as well as other burn-related healthcare resource use which will also be recorded for each participant. This will be inclusive of labour time (e.g. allied health, nurses and doctors/surgeons) and consumables (e.g. splints) in clinic settings, as well as inpatient admission-related resource use where relevant (e.g., inpatient admissions for burn-related procedures).
Timepoint [15] 342988 0
At each dressing change and at the 3, 6, and 12 month post burn injury follow up visit
Secondary outcome [16] 346440 0
Adjunct Interventions.
Distraction Techniques utilised prior to change of dressing will be noted.
Timepoint [16] 346440 0
At initial dressing application and each dressing change, until 95% or more wound re-epithelialisation as determined by the attending burns surgeon.
Secondary outcome [17] 346441 0
Wound Intervention Fidelity:
A checklist will be completed for each intervention group to assess the adherence by clinical staff to the intervention protocol.
Timepoint [17] 346441 0
At initial dressing application and each dressing change, until 95% or more wound re-epithelialisation as determined by the attending burns surgeon.

Eligibility
Key inclusion criteria
1. Age 16 years or older
2. Burn depth of superficial partial to mid-dermal thickness burns
3. Able to be recruited and treated within 48hours of burn injury
4. TBSA 5% or greater
Minimum age
No limit
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Burn depth of superficial, deep dermal or full thickness depth
2. Patients whose injuries are deemed not compatible with life by the attending burns surgeon

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)
Treating physicians/nursing staff of all children meeting the inclusion/exclusion criteria presenting to the Lady Cilento Children’s Hospital, Brisbane will determine eligibility for enrolment in the study. With the parent/caregivers permission an investigator aligned with the study will discuss the study with the parents/caregivers and seek informed consent within 48 hours of the burn injury occurring. Once informed consent is obtained, participants will be randomised to one of three treatment groups. Randomisation will be undertaken by use of a randomisation sequence embedded into the REDCap data collection application by a third party not aligned with the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation sequence will be verified by statistician before upload onto the REDCap software application.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Data will be graphed and summary statistics calculated for all outcomes. Where appropriate, non-parametric tests will be used. A survival analysis will be utilised, with the time to re-epithelialisation as the main outcome and dressing group as the explanatory variable. All other dataset will be analysed using appropriate methods for longitudinal data such as mixed model’s regression analysis or Generalised Estimating Equations (GEE). A p value of 0.05 will be considered statistically significant. The sample size calculation, and methodology regarding randomisation of the cohort and statistical analysis was finalised in consultation with a biostatistician.

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)
QLD

Funding & Sponsors
Funding source category [1] 298355 0
Commercial sector/Industry
Name [1] 298355 0
Avita Medical Asia Pacific
Address [1] 298355 0
AVITA MEDICAL ASIA PACIFIC
Suite G.01, 68 South Terrace,
South Perth, WA, 6151, Australia
Country [1] 298355 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
2 George St,
Brisbane City
QLD
4000
Country
Australia
Secondary sponsor category [1] 297716 0
Commercial sector/Industry
Name [1] 297716 0
Avita Medical
Address [1] 297716 0
AVITA MEDICAL ASIA PACIFIC
Suite G.01, 68 South Terrace,
South Perth, WA, 6151, Australia
Country [1] 297716 0
Australia
Other collaborator category [1] 280099 0
Individual
Name [1] 280099 0
Dr Zephanie Tyack
Address [1] 280099 0
Centre for Children's Burns and Trauma Research Children's Health Research Centre 62 Graham Street, South Brisbane, QLD, 4101.
School of Public Health and Social Work, Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia, 4001
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia, 4006
Country [1] 280099 0
Australia
Other collaborator category [2] 280100 0
Individual
Name [2] 280100 0
Prof Steven M. McPhail
Address [2] 280100 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 [2] 280100 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299350 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 299350 0
Level 7, Centre for Children’s Health Research, Queensland Children’s Hospital Precinct, 62 Graham St, South Brisbane QLD 4101
Ethics committee country [1] 299350 0
Australia
Date submitted for ethics approval [1] 299350 0
20/11/2017
Approval date [1] 299350 0
21/12/2017
Ethics approval number [1] 299350 0
HREC/17/QRCH/278

Summary
Brief summary
The RECELL® autologous cell harvesting device enables rapid autologous epidermal replacement. The paucity of data substantiating its implementation in acute paediatric burn injuries warrants further evaluation. This study aims to compare effectiveness of three commercially available burn wound management approaches used for burn injuries. Informed consent of parent/guardians of children meeting the inclusion criteria will be obtained the demographic data collected. Participants will be randomised to standard silver dressing or Biobrane® with RECELL® or Biobrane® only. These will be initially applied under a general anaesthetic in the operation theatre. Data acquisition will be from digital imaging, sonography, colorimetry and assessments of pain, itch, dressing application ease, treatment satisfaction, intervention fidelity, health- related quality of life, scar assessment and health resource utilisation will be recorded. Intervals for data collection will be at baseline, at all 3-5 day dressing changes until wound is 95% or more re-epithelialised and at outpatient follow up at 3, 6 and 12 months post injury.

Trial website
Trial related presentations / publications
Presentation:
1. IHBI Insires 2018 (Brisbane, QLD, Australia): "Spray-on Skin® and mixed partial thickness paediatric burns: The BRACS Trial"
2. ANZBA ASM 2018 (Brisbane, QLD, Australia): "Autologous skin cell suspensions and Partial thickness Paediatric burns: The BRACS Trial Protocol"
3. Cutaneous Biology Meeting 2018 (North Stradbroke Island, QLD, Australia): "A comparison of the effectiveness of Biobrane®, RECELL® Autologous Skin Cell Suspension and Silver Dressings in superficial partial to mid-dermal thickness paediatric burns: The BRACS Randomised Trial."
Public notes

Contacts
Principal investigator
Name 80146 0
Prof Roy Kimble
Address 80146 0
Service Group Director, Paediatric Surgery, Urology, Neonatal Surgery, Burns & Trauma
Clinical Lead, Paediatric Vascular Anomalies,
Director of the Centre for Children’s Burns & Trauma Research
University of Queensland Professor of Paediatrics & Child Health
PO Box 3474, South Brisbane, Qld, 4101

Country 80146 0
Australia
Phone 80146 0
+61 7 3068 5624
Fax 80146 0
+61 7 30683799
Email 80146 0
royk@uq.edu.au
Contact person for public queries
Name 80147 0
Dr Bronwyn Griffin
Address 80147 0
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 80147 0
Australia
Phone 80147 0
+61730697392
Fax 80147 0
Email 80147 0
bronwyn.griffin@qut.edu.au
Contact person for scientific queries
Name 80148 0
Dr Bronwyn Griffin
Address 80148 0
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 80148 0
Australia
Phone 80148 0
+61730697392
Fax 80148 0
Email 80148 0
bronwyn.griffin@qut.edu.au

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 other documents available
Summary results
No Results