ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621000288820

Ethics application status

Approved

Date submitted

18/01/2021

Date registered

16/03/2021

Date last updated

21/03/2022

Date data sharing statement initially provided

16/03/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

A randomised controlled trial of ablative fractional CO2 laser and medical needling in children with burn scars

Scientific title

A randomised controlled trial of ablative fractional CO2 laser and medical needling in children with burn scars

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1262-4691

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Burn scars

Condition category

Condition code

Skin

Other skin conditions

Injuries and Accidents

Burns

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention arm 1 - Ablative fractional CO2 laser therapy + standard care: Ablative fractional CO2 laser therapy will be delivered by a surgeon to each participant under a general anaesthetic using a Lumenis Ablative Fractional CO2 laser with SCAAR FX setting; ARTG no. 182239. The dosage applied by the laser intervention will be delivered at one of three depth settings (1-2mm, 60-70mj – shallow skin lesion, 2-3mm, 70-120mj – medium skin lesion, >3mm, 120-150mj – deep skin lesion), which will be determined by ultrasound measurement of scar thickness pre-operatively; and with a standard device setting of 1% density, square size 10, 250Hz, 1 pass with minimal overlapping. The dose applied and areas these doses were applied will be recorded as part of a fidelity checklist. Delivered individually over 1 session at 6 months or more post-burn. Following the intervention any blood and/or exudate will be cleaned, the site will be covered with a Sorbact dressing immediately post-intervention for 24 hours and following that QV intensive moisturising cream will be applied as many times a day as needed to prevent dryness of the skin site. The duration of the intervention will vary for each participant and will be determined by the treating surgeon but will usually be for no longer than 1 hour under general anaesthetic. A hospital-specific factsheet will be provided to the caregivers of participants with post-procedural information (e.g. ongoing treatment, aftercare of the treatment site). Standard care (see below) will continue with the exception of brief cessation of standard care interventions post-operatively. Silicone and pressure garment therapy will be recommenced after re-epithelialisation post laser intervention where appropriate.

Intervention arm 2 - Medical needling + standard care: Medical needling will be delivered mechanically by a surgeon to each patient under a general anaesthetic using 3mm needles attached to a roller (Environ Roll-CIT 3mm). The dose applied and areas these doses were applied will be recorded as part of a fidelity checklist. Delivered individually in 1 session at 6-months or more post-burn. Following the intervention any blood and/or exudate will be cleaned, the site will be covered with a Sorbact dressing immediately post-intervention for 24 hours and following that QV intensive moisturising cream will be applied as many times a day as needed to prevent dryness of the skin site. The duration of the intervention will vary for each participant and will be determined by the treating surgeon but will usually be for no longer than 1 hour under general anaesthetic. A hospital-specific factsheet will be provided to the caregivers of participants with post-procedural information (e.g. ongoing treatment, aftercare of the treatment site). Standard care (see below) will continue with the exception of brief cessation of standard care interventions post-operatively. Silicone and pressure garment therapy will be recommenced after re-epithelialisation post needling as appropriate.

NB: Standard care may include pressure garments, silicone products, skin or scar massage, exercises, moisturisers, education regarding sun protection. The dose and type of interventions provided is determined by treating health professionals. One or more of these interventions may be provided.

Intervention code [1]

Treatment: Devices

Intervention code [2]

Treatment: Surgery

Comparator / control treatment

There is no placebo group in this study as we are comparing one intervention to the other. Therefore the laser therapy intervention (reference comparator) will be compared to medical needling.

Control group

Active

Outcomes

Primary outcome [1]

Scar thickness measured using high frequency ultrasound

Timepoint [1]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure (primary endpoint).

Secondary outcome [1]

Scar pigmentation measured using the DSM-II ColorMeter L* parameter

Timepoint [1]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [2]

Scar pigmentation measured using the DSM-II Colormeter melanin parameter.

Timepoint [2]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [3]

Burn-scar specific, health-related quality of life (child itch severity). Brisbane Burn Scar Impact Profile itch items. Reported by parent proxies or children aged 8 years or older.

Timepoint [3]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 48 hours, 1 month and 3 months post-procedure.

Secondary outcome [4]

Burn-scar specific, health-related quality of life (child pain severity). Brisbane Burn Scar Impact Profile pain items. Reported by parent proxies or children aged 8 years or older.

Timepoint [4]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 48 hours, 1 month and 3 months post-procedure.

Secondary outcome [5]

Burn-scar specific, health-related quality of life (perceived scar tightness). Brisbane Burn Scar Impact Profile scar tightness items. Reported by parent proxies or children aged 8 years or older.

Timepoint [5]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at a 1 month and 3 months post-procedure

Secondary outcome [6]

Burn-scar specific, health-related quality of life (child appearance). Brisbane Burn Scar Impact Profile appearance subscale. Reported by parent proxies or children aged 8 years or older.

Timepoint [6]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at a 1 month and 3 months post-procedure

Secondary outcome [7]

Burn-scar specific, health-related quality of life (child daily living). Brisbane Burn Scar Impact Profile daily living subscale. Reported by parent proxies or children aged 8 years or older.

Timepoint [7]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at a 1 month and 3 months post-procedure

Secondary outcome [8]

Generic health-related quality of life: CHU-9D utility measure. Reported by parent proxies or children aged 8 years or older.

Timepoint [8]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [9]

School functioning: PEDS-QL school functioning subscale. Reported by children aged 8 years or older.

Timepoint [9]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and 1 month and 3 months post-procedure.

Secondary outcome [10]

Days missed from school or daycare: a single question for the number of days missed from school or daycare reported by parent proxies or children aged 8 years or older

Timepoint [10]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and 1 month and 3 months post-procedure.

Secondary outcome [11]

Days missed from employment: a single question for number of days missed from employment self-reported by a caregiver.

Timepoint [11]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and 1 month and 3 months post-procedure.

Secondary outcome [12]

Satisfaction with scar response to treatment measured using a 0 to 10 numeric rating scale. Data will be gathered from patients aged 8 years and older and all parents/caregivers.

Timepoint [12]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [13]

Adverse effects to the laser intervention may include redness, changes in pigmentation (hyperpigmentation or hypopigmentation), a hypersensitive scar, blistering and irritation around hair follicles, infection, scarring, swelling and bruising for 7 to 10 days after the procedure. This outcome will be measured by participant/proxy self-report using a study-specific questionnaire.

Adverse effects to the medical needling intervention may include swelling, tingling, and redness for a day or more.

Timepoint [13]

Measured after intervention, at 48 hours, 1 month and 3 months post-procedure and continuously throughout the trial. Will be measured by participant/proxy-self report using a free text option in electronic questionnaires or as verbally reported to researchers by treating health professionals.

Secondary outcome [14]

Burn-scar specific, health-related quality of life (child friendships and social interaction). Brisbane Burn Scar Impact Profile friendships and social interaction subscale. Reported by parent proxies or children aged 8 years or older.

Timepoint [14]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [15]

Burn-scar specific, health-related quality of life (child mobility). Brisbane Burn Scar Impact Profile mobility subscale. Reported by parent proxies or children aged 8 years or older.

Timepoint [15]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [16]

Burn scar specific health-related quality of life (child overall impact) - Brisbane Burn Scar Impact Profile overall impact subscale

Timepoint [16]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [17]

Burn scar specific health-related quality of life (child emotional reactions) - Brisbane Burn Scar Impact Profile emotional reactions subscale

Timepoint [17]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Secondary outcome [18]

Burn scar specific health-related quality of life (child physical symptoms) - Brisbane Burn Scar Impact Profile physical symptoms subscale.

Timepoint [18]

This outcome will be measured at baseline (6-months or more post-burn; prior to randomisation) and at 1 month and 3 months post-procedure.

Eligibility

Key inclusion criteria

Participants will be aged 18 years or younger at the time of recruitment and have:
• Hypertrophic burn scarring of any size at 6-months or more post-burn with functional and/or cosmetic implications determined by patient-report on the Brisbane Burn Scar Impact Profile.
• Able to attend the study sites for treatment and follow-up.

Minimum age

No limit

Maximum age

18 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Participants will not be included if they have:
• Previously received laser therapy or medical needling as part of treatment for their burn scars
• Hypersensitivity to light/laser treatments as laser therapy would be contraindicated;
• Co-morbid skin disorders (i.e., current eczema, dermatitis, skin cancer) as these could confound wound healing and scarring post-intervention.

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)

Central randomisation by computer

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Stratified allocation will be used in the study with scar thickness of the treatment site (<2mm, greater than or equal to 2mm) as the unit of stratification. Randomisation will be at the level of the individual in random blocks.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Thirty participants in each arm are required to be able to detect a between-group effect
size of 0.75 standard deviation Z-scores or greater with 80% power (alpha=0.05) for the
primary outcome of ultrasound scar thickness. To account for expected 15% attrition 1-
month post-procedure, an additional 10 participants are required. In total we will recruit at least 70 participants (35 participants per group) over a 7-month timeframe. It is expected that the study interventions will be delivered over a 10 month period, with a 3 month post-intervention follow-up.

Primary outcome comparison post-procedure will be based on the change in ultrasound scar thickness compared between the laser therapy and medical needling groups using generalised linear mixed models for repeated measures. The primary outcome comparison will be conducted using an intention to treat approach. This will be compared to a per-protocol approach. A sensitivity analysis will be conducted using imputation techniques to replace non-ignorable data that is considered to be missing at random over the follow-up period, to determine whether bias is likely in the complete case analysis. Secondary outcome comparisons will be conducted at 1-month and 3-months post procedure using linear mixed models or generalised estimating equations where appropriate. Prespecified secondary analyses will examine the influence of the child’s age, gender, body location of the treated scar, skin type, and scar visibility and previous surgical intervention on the treatment response using the outcomes of ultrasound scar thickness, itch, and overall opinion of the scar appearance where possible. A sensitivity analysis will investigate whether a mean difference measure of scar thickness, vascularity and pigmentation between the selected scarred skin and an uninjured contralateral skin site changes the results of the primary approach that uses the selected scarred skin alone. Descriptive results may be reported where the assumptions of other chosen analyses are not met. Qualitative data will be collected to further investigate the physical and sensory scar outcomes, evidence of the laser and medical needling intervention group allocation, acceptability of the interventions and patient-reported outcome measures, and feasibility of the interventions. Framework analysis will be used to analyse the qualitative findings.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/04/2021

Actual

29/06/2021

Date of last participant enrolment

Anticipated

1/11/2022

Actual

Date of last data collection

Anticipated

1/01/2023

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Queensland Children's Hospital - South Brisbane

Recruitment postcode(s) [1]

4101 - South Brisbane

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Children's Hospital Foundation

Address [1]

501 Stanley Street
South Brisbane QLD 4101

Country [1]

Australia

Primary sponsor type

University

Name

The University of Queensland

Address

Child Health Research Centre
62 Graham St.
South Brisbane QLD 4101

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Children's Health Queensland

Address [1]

Queensland Children's Hospital
501 Stanley St, South Brisbane QLD 4101

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Children’s Health Queensland Human Research Ethics Committee

Ethics committee address [1]

Children's Health Queensland Hospital and Health Service Human Research Ethics Committee
Level 7, Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
Level 7, 62 Graham Street
South Brisbane QLD 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

02/08/2018

Approval date [1]

01/02/2021

Ethics approval number [1]

Summary

Brief summary

Managing scarring remains a significant challenge despite global reductions in burn incidence and severity of burn scars over the last 30 years. Ablative fractional CO2 laser therapy and medical needling are potentially revolutionary and minimally invasive interventions to treat severe burns scars. Laser and needling produce microscopic holes in scar tissue and this process is thought to assist scar tissue remodelling. Needling may have some advantages over laser in terms of feasibility. As there has been minimal investigation of laser and medical needling in children with severe burn scars, there is an urgent need to conduct a rigorous trial within this population. A randomised controlled trial will be conducted at a specialist children’s hospital with a sample of children with severe burn scars. Children will be randomised to one of two intervention groups: ablative fractional CO2 laser therapy or medical needling. The primary outcome of this trial will be ultrasound-assessed scar thickness post-intervention.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Zephanie Tyack

Address

The University of Queensland
62 Graham St.
South Brisbane QLD 4101

Country

Australia

Phone

+61 7 3069 7343

Fax

[email protected]

Contact person for public queries

Name

Dr Zephanie Tyack

Address

The University of Queensland
62 Graham St.
South Brisbane QLD 4101

Country

Australia

Phone

+61 7 3069 7343

Fax

[email protected]

Contact person for scientific queries

Name

Dr Zephanie Tyack

Address

The University of Queensland
62 Graham St.
South Brisbane QLD 4101

Country

Australia

Phone

+61 7 3069 7343

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
10271	Study protocol				This document will be uploaded once published.
10272	Statistical analysis plan				This document will be uploaded prior to the end of... [More Details]

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.

Trial Review

Documents added manually

Documents added automatically