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Trial registered on ANZCTR


Registration number
ACTRN12618000256279
Ethics application status
Approved
Date submitted
13/02/2018
Date registered
16/02/2018
Date last updated
13/10/2020
Date data sharing statement initially provided
6/05/2019
Date results information initially provided
6/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of Negative Pressure Wound Therapy as an Adjunctive Treatment for Acute Burns in Children - A Randomised Controlled Trial
Scientific title
The Effect of Negative Pressure Wound Therapy on Re-epithelialisation, Pain, and Wound
Progression in Acute Paediatric Burns – A Randomised Controlled Trial
Secondary ID [1] 293831 0
None
Universal Trial Number (UTN)
U1111-1208-1959
Trial acronym
SONATA in C
Linked study record
Pilot study: ACTRN12614001068651

Health condition
Health condition(s) or problem(s) studied:
Paediatric burns 306261 0
Acute burns 306607 0
Condition category
Condition code
Injuries and Accidents 305365 305365 0 0
Burns
Skin 305706 305706 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients allocated to the intervention group will have their wounds first dressed in the Pegg Leditschke Paediatric Burns Centre (PLPBC) or the Lady Cilento Children's Hospital Emergency Department (ED) with a combination of standard dressings (Acticoat™ and Mepitel™). Additionally, an experienced burns clinician will provide these patients Negative Pressure Wound Therapy (NWPT) using a RENASYS TOUCH™ (Hull, UK, Smith & Nephew) suction device set at a continuous pressure of -80 mmHg. These therapies will be administered at the time of randomisation and replaced every 3-5 days until the burn is 95% re-epithelialised, or until grafting is required.
Intervention code [1] 300092 0
Treatment: Devices
Comparator / control treatment
The same experienced burns clinicians involved in the care of the intervention group will treat the control group in the PLPBC or ED with a combination of standard dressings (Acticoat™ and Mepitel™, secured with hypafix). These dressings will be provided at the time of randomisation and replaced every 3-5 days until the burn is 95% re-epithelialised, or until grafting is required. Feeding tubes will be incorporated into the dressings to allow for regular irrigation at home by the patients' guardians.
Control group
Active

Outcomes
Primary outcome [1] 304512 0
Time to re-epithelialisation, as measured by the number of days from the injury to 95% re-epithelialisation of the burn wound. Percentage re-epithelialisation will be evaluated using 2 methods: (1) a treating consultant will perform an examination and record their assessment at every clinical visit; and (2) digital 3D photographs will be taken of the burn at each dressing change and undergo analysis on the Dermapix™ and/or 3D WoundCare™ software program as well as blinded review by a panel of 3 burns surgeons.
Timepoint [1] 304512 0
Every 3-5 days (i.e., at each dressing change) after intervention commencement until the wound is 95% re-epithelialised.
Secondary outcome [1] 342206 0
Impact of interventions on pain during dressing changes.

A variety of measures and age-dependent scales will be used to assess pain: (1) nurses’ observational rating using the face, legs, activity, cry, consolability (FLACC) scale; (2) child self-report via the Revised Faces Pain Scale (FPS-R) for patients aged 4-7 years and the Numerical Rating Scale (NRS) for patients 8 years and older; (3) parents' report using the NRS; and (4) any analgesic and/or sedative medications administered to the participant during clinical visits.
Timepoint [1] 342206 0
Every 3-5 days in clinic during dressing changes until the wound is fully re-epithelialised.
Secondary outcome [2] 342207 0
Impact of interventions on pain between dressing changes (at-home measures). Participants will be contacted via SMS or email and prompted to complete a brief online survey containing: (1) the child's self-report using the Revised Faces Pain Scale (FPS-R) for patients aged 4-7 years and the Numerical Rating Scale (NRS) for patients 8 years and older; and (2) the parents' report using the NRS.
Timepoint [2] 342207 0
Participants will be asked to provide pain scores 24-48 hours following every clinical visit until the wound is fully re-epithelialised.
Secondary outcome [3] 342208 0
Ease of intervention management. The ease of removing and applying the dressings and/or NPWT system will be obtained from the treating nurse(s) on an 11-point Numerical Rating Scale (NRS).
Timepoint [3] 342208 0
Every 3-5 days (i.e., at each dressing change) after intervention commencement until the wound is 95% re-epithelialised.
Secondary outcome [4] 342210 0
Impact of interventions on itch severity during dressing changes. Caregivers will provide observational assessments using the Toronto Paediatric Itch Scale for patients 5 years and younger, whilst older participants will self-report via the Itch Man Scale.
Timepoint [4] 342210 0
Every 3-5 days in clinic during dressing changes until the wound is fully re-epithelialised.
Secondary outcome [5] 342211 0
Impact of interventions on itch severity between dressing changes (at-home measures). Participants will be contacted via SMS or email and prompted to complete a brief online survey assessing itch severity via the Toronto Paediatric Itch Scale and the Itch Man Scale.
Timepoint [5] 342211 0
Participants will be asked to provide itch scores 24-48 hours following every clinical visit until the wound is fully re-epithelialised.
Secondary outcome [6] 342950 0
Wound progression.

Wound depth will be assessed using laser doppler imaging.
Timepoint [6] 342950 0
At their initial dressing application and their first dressing change 3-5 days later.
Secondary outcome [7] 342962 0
Adverse events.

Minimal adverse events are expected, as NPWT is a TGA-approved product associated with very little risk. Known potential adverse events include infection, adverse skin reactions, bleeding, and vascular compression. Participants, caregivers, and/or clinicians will report adverse events to investigators.
Timepoint [7] 342962 0
Every 3-5 days (i.e., at each dressing change) after intervention commencement until the wound is 95% re-epithelialised.
Secondary outcome [8] 342963 0
Ease of intervention management at home. Caregivers and patients 8 years and older will assess the ease of managing their dressings at home using a 0-10 Numeric Rating Scale.
Timepoint [8] 342963 0
Every 3-5 days (i.e., at each dressing change) after intervention commencement until the wound is 95% re-epithelialised.
Secondary outcome [9] 343023 0
Wound fluid analysis.

Mass spectrometric analyses will be performed on samples of wound fluid collected in NPWT canisters to provide a proteomic/metabolomic profile of their contents.
Timepoint [9] 343023 0
Wound fluid will be collected every 3-5 days (i.e., at each NPWT change) after intervention commencement until the wound is 95% re-epithelialised.
Secondary outcome [10] 343076 0
Cost effectiveness of interventions.

Expenses will be costed at market rates and will include trial interventions costs (e.g. the number of dressing changes, the type and size of dressings used, the number of nurses required for each dressing change), scar therapy products, and grafting requirements.
Timepoint [10] 343076 0
Every 3-5 days (i.e., at each dressing change), at the point of healing, and at follow-up appointments at 3 and 6 months post-injury.
Secondary outcome [11] 343096 0
Scar assessment.

Scar assessments will be performed using the Patient and Observer Scar Assessment Scale (POSAS), Brisbane Burn Scar Impact Profile, digital photography, and colorimetry. Additionally, ultrasound will be used to determine scar thickness and the ratio of scar thickness to normal adjacent skin. Measures will be taken by a blinded assessor.
Timepoint [11] 343096 0
At the point of healing, and at follow-up appointments at 3 and 6 months post-injury.
Secondary outcome [12] 346418 0
Physical function. Participants’ physical function while undergoing treatment will be assessed at every clinical visit via an 11-point NRS.
Timepoint [12] 346418 0
Every 3-5 days (i.e., at each dressing change) after intervention commencement until the wound is 95% re-epithelialised.

Eligibility
Key inclusion criteria
Children aged 0-16 years presenting with a thermal burn to the Emergency Department or Pegg Leditschke Children’s Burns Centre at the Lady Cilento Children’s Hospital, Brisbane, within 7 days post-injury.
Minimum age
No limit
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Burns covering 5% or more of the total body surface area (TBSA)
• Trivial burns (at the discretion of the burns surgeon)
• Facial burns

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)
Randomisation will be undertaken using the central randomisation module on the Research Electronic Data Capture (REDCap; Vanderbilt University, Nashville, US) application, which assures allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation

Participants will be stratified by age. Stratification will occur at the time of randomisation into 3 groups:

1. Age 0-3 years
2. Age 4-7 years
3. Age 8-16 years
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size estimate was calculated based on the primary outcome of time to re-epithelialisation.

Descriptive statistics will be reported as mean and standard deviation (SD) for normally distributed continuous data or median and interquartile range (IQR) for non-normally
distributed data. Categorical variables will be presented as frequencies and percentages.
The potential effect of time to treatment, burn depth, burn total body surface area, mechanism of injury, anatomical location of the burn, and skin type will also be tested against primary and secondary measures in a univariate analysis. All variables with a p-value <0.2 will be included in a stepwise multiple linear regression to analyse the effect of these factors when considered in combination.

A linear mixed model will be performed to determine the evolution across time and between groups in primary and secondary outcomes, with patients as random effect. The fixed effects of time, group and interaction time by group will be tested. Data will be analysed as intention to treat and on a per protocol basis. Any missing data will be handled using the multiple imputation method where appropriate. Significance will be set at 0.05. All statistical analyses will be performed using SPSS 21 (IBM Corp., Armonk, NY, USA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/03/2018
Actual
2/05/2018
Date of last participant enrolment
Anticipated
31/12/2018
Actual
15/01/2019
Date of last data collection
Anticipated
31/12/2019
Actual
29/06/2019
Sample size
Target
104
Accrual to date
Final
114
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9841 0
Lady Cilento Children's Hospital - South Brisbane

Funding & Sponsors
Funding source category [1] 298446 0
Commercial sector/Industry
Name [1] 298446 0
Smith and Nephew Australia
Country [1] 298446 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Level 6, 62 Graham Street, South Brisbane, QLD, 4101
Country
Australia
Secondary sponsor category [1] 297590 0
Hospital
Name [1] 297590 0
Lady Cilento Children's Hospital
Address [1] 297590 0
501 Stanley St, South Brisbane QLD 4101
Country [1] 297590 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299441 0
Children's Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 299441 0
Level 7, Centre for Children's Health Research, 62 Graham St, South Brisbane, QLD 4101
Ethics committee country [1] 299441 0
Australia
Date submitted for ethics approval [1] 299441 0
20/11/2017
Approval date [1] 299441 0
08/12/2017
Ethics approval number [1] 299441 0
HREC/17/QRCH/279

Summary
Brief summary
Background: Although Negative Pressure Wound Therapy (NPWT) has become widely used in the management of several wound types, its efficacy as a primary therapy for acute burns has never been adequately investigated, with research in children particularly lacking. There is limited evidence, however, that NPWT might benefit paediatric burns patients, amongst whom scar formation, wound progression, and pain continue to present major management challenges. The purpose of this trial is to determine whether NPWT in conjunction with standard therapy accelerates healing, reduces wound progression, and decreases pain more effectively than routine treatment alone.

Methods: A total of 96 paediatric burns patients will be recruited for this trial. To be eligible, candidates must be under 17 years of age and present with a thermal burn covering <5% of their total body surface area to the participating children’s hospital within 7 days of their injury. Facial and trivial burns will be excluded. Following a randomised controlled, parallel design, participants will be allocated to either an active control or intervention group. The former will receive standard therapy consisting of Acticoat™ and Mepitel™, secured with Hypafix™. The intervention arm will be treated with silver-impregnated dressings in addition to NPWT via the RENASYS TOUCH™ vacuum pump. Participants will undergo dressing changes every 3-5 days until the point of healing. The primary endpoint will be time to re-epithelialisation. Secondary outcomes include pain, pruritus, wound progression, cost effectiveness, ease of management, treatment satisfaction, and adverse events. A linear mixed model will be performed to determine the evolution across time and between groups in primary and secondary outcomes, with patients as random effect. Wound fluid collected during NPWT will also be analysed to generate a proteomic profile of the burn microenvironment.

Discussion: The study will be the first randomised controlled trial to explore the effects of NPWT on paediatric burns, with the aim of determining whether the therapy warrants implementation as an adjunct to standard burns management.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80414 0
Dr Bronwyn Griffin
Address 80414 0
Level 7, Centre for Children's Health Research, The University of Queensland, 62 Graham St, South Brisbane, QLD 4101
Country 80414 0
Australia
Phone 80414 0
+61 7 3069 7392
Fax 80414 0
Email 80414 0
b.griffin@uq.edu.au
Contact person for public queries
Name 80415 0
Mr Cody Frear
Address 80415 0
Level 7, Centre for Children's Health Research, The University of Queensland, 62 Graham St, South Brisbane, QLD 4101
Country 80415 0
Australia
Phone 80415 0
+61 4 0535 3151
Fax 80415 0
Email 80415 0
cody.frear@uqconnect.edu.au
Contact person for scientific queries
Name 80416 0
Mr Cody Frear
Address 80416 0
Level 7, Centre for Children's Health Research, The University of Queensland, 62 Graham St, South Brisbane, QLD 4101
Country 80416 0
Australia
Phone 80416 0
+61 4 0535 3151
Fax 80416 0
Email 80416 0
cody.frear@uqconnect.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data underlying published results
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1976Study protocolFrear CC, Griffin B, Cuttle L, McPhail SM, Kimble R. Study of negative pressure wound therapy as an adjunct treatment for acute burns in children (SONATA in C): protocol for a randomised controlled trial. Trials. 2019 Dec;20(1):130.   https://trialsjournal.biomedcentral.com/articles/1... [More Details]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Publication date: 14 September 2020 Citation: F... [More Details] 374339-(Uploaded-09-10-2020-15-02-59)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseStudy of negative pressure wound therapy as an adjunct treatment for acute burns in children (SONATA in C): Protocol for a randomised controlled trial.2019https://dx.doi.org/10.1186/s13063-019-3223-9
EmbaseRandomized clinical trial of negative pressure wound therapy as an adjunctive treatment for small-area thermal burns in children.2020https://dx.doi.org/10.1002/bjs.11993
N.B. These documents automatically identified may not have been verified by the study sponsor.