Hypothesis and Objectives
It is hypothesised that NPWT is feasible, acceptable and safe in paediatric hand and foot burns. Furthermore; it is also hypothesised that by utilising NPWT, burns will have a decreased time to re-epithelialisation, and reduced pain, itch, infection and scar formation.
The primary objectives of this pilot study are to determine the feasibility, acceptability and safety of the use of NPWT in paediatric hand and foot burns. The secondary objectives will include investigating time to re-epithelialisation, pain, itch and scar formation. If further research is required, this pilot will help guide the methodology of a larger RCT. Ultimately, this study may inform the integration of NPWT into routine, acute paediatric burns care.
Trial design
This study is a parallel-group, two-armed, single center, pilot, randomized trial contrasting the outcomes of burns patients treated with 1) standard dressings of Mepitel® and ACTICOAT™ (approximately 15 patients, control) against 2) standard dressings plus a NPWT RENASYS TOUCH™ device (approximately 15 patients, intervention). An overview of the study design is summarized in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure (Fig. 1) and the SPIRIT checklist (Supplement 1).
Study setting
This study will be set at the Pegg Leditschke Children’s Burns Centre (PLCBC), Queensland Children’s Hospital (QCH), Brisbane, Australia. QCH is a quaternary specialist paediatric hospital with the burns centre catchment area boundaries including central and southern Queensland and nothern New South Wales, an estimated area of 1,053,700 km2 with a population of 4.5 million people.
Eligibility criteria
Participants will include approximately 30 children that are equal to or less than 16 years of age with a burn that is on the hand or foot (may be in the context of a larger burn), managed within 24 hours of sustaining the injury and is either superficial partial thickness and > 0.5% TBSA on one hand or foot or any sized burn that is deep or full thickness. The patient will be excluded if clinician treatment priority contradicts study enrollment, they do not wish to participate, the child is acutely unwell at the time of presentation or consent is unable to be confirmed within 24 hours of sustaining the burn injury (Table 1).
Table 1
Inclusion Criteria | Exclusion Criteria |
Hand or foot burn, may be in the context of a larger burn | Clinician treatment priority contradicts randomization |
≤ 16 years of age | Do not wish to participate |
Managed ≤ 24 hours of sustaining a burn injury | Consent unable to be confirmed within 24hours of sustaining burn injury |
Superficial partial thickness burn ≥ 0.5% TBSA on one hand or foot | The child is acutely unwell at the time of presentation |
Any sized burn that is deep partial or full thickness | |
Recruitment/Consent
Burns Team and/or Emergency Department (ED) staff will notify researchers of eligible participants presenting to either the ED or the PLCBC. An investigator will provide the patient/family with information (both verbal and written) on the trial and if the patient/family agrees, they will be asked to sign a consent. Where the participant does not speak English as their first language, an interpreter will be offered. A third party will be present throughout to ensure no coercion and will also sign the consent. If the family does not agree, they will be asked to consent to their baseline demographic data being included. When consenting, it is ensured that the participants/families know they have the autonomy to withdraw from the study at any stage.
Throughout the participants treatment, researchers will be independent of any clinical decision making processes regarding the participants. Treating clinicians will decide where the debridement occurs (ie theatre, ED, PLCBC) and whether it is appropriate for the patient to be enrolled in the study. Demographic data (ie. Burn details, medical, surgical and social history) will be collected before randomisation into the study.
Intervention
For all trial patients, appropriate analgesia will be given via either a general anaesthetic or analgesia +/- procedural sedation. Next, the burn will be debrided with water and QV Gentle Wash (Ego Pharmaceuticals, Sydney, Australia) and then 10ml of 5% chlorhexidine gluconate in 500mL of water. Patients will then have treatment according to the group they were allocated to:
Control participants will receive the standard dressings currently applied at the PLCBC for burns. Mepitel® (Mölnlycke Healthcare, Mikkeli, Finland) and ACTICOAT™ (Smith & Nephew, Hull, UK) will be placed over the burn and secured with Hypafix™ (BSN Medical, Hamburg, Germany). These dressings will by changed every three to seven days (reflective of clinical practice) and continued until the burn is deemed re-epithelialised by the treating clinician. Data will be gathered at each dressing change.
Intervention participants will include application of the RENASYS TOUCH™ device (Smith & Nephew, Hull, UK) in addition to standard dressings. Kerlix™ AMD Antimicrobial bandage roll (CardinalHealth, Dublin, USA) is first placed as an interface between the standard dressings and NPWT device, then a Suprasorb® CNP EasyDress sleeve (Lohmann & Rauscher, Rengsdorf, Germany) applied over the standard dressing + Kerlix™ and secured with the provided film (+/- additional semi-permeable transparent film dressing as required to achieve seal). A small hole (< 30mm) will be cut in the Suprasorb® CNP EasyDress sleeve over the site of the burn and a soft port applied over the hole, ensuring the hole in the EasyDress aligns with the hole of the soft port. The soft port is then attached to a cannister which is attached to the RENASYS TOUCH™ NPWT device. Suction will be applied continuously at either 80mmHg for children > 1 years old, 60mmHg for 6months – 1 year or 40mmHg < 6 months old. If bilateral hands and/or feet are involved, the deeper one will have NPWT applied. If both are assessed to be of equal depth then NPWT with a y connector will be used. The NPWT will remain on for the first 3–7 days and then removed at the first dressing change, it will not be reapplied after this. Once the NPWT is removed, treatment will continue as per the control group with standard dressings.
Throughout the trial, strategies to improve NPWT adherence will include a backpack to carry the device, dressing packs on discharge that include extra tape to help seal any leaks, education (both written and verbal) on the device and where to call to help trouble shoot issues on discharge.
Criteria for discontinuing or modifying allocated interventions for a given trial participant will include: on debridement of the burn, it no longer meets the eligibility criteria (ie burn is actually only SPT and is < 0.5% TBSA) or there is an adverse outcome requiring at least admission to the Paediatric Intensive Care Unit (PICU). Patients who become septic but are not admitted to PICU or require grafting will remain in the study.
Relevant concomitant care and interventions will include patients in the standard group receiving occupational therapy input including potential splinting from initial presentation. If required, patients in the NPWT group will only commence splinting once the NPWT is removed. The hand will be positioned in a neutral position whilst the NPWT is applied. Kerlix™; an antimicrobial crepe gauze, will aid in maintaining this position and splinting the wound whilst the NPWT is applied.
Assignment of interventions (Randomisation)
Sequence generation will be done via a computer, automated, centralized, randomisation program hosted by the Griffith Randomisation Service. The participants will be in randomized in permutated blocks of sizes two and four so the primary investigator cannot predict the allocation sequence. The participants will be stratified based on whether they are a hand vs foot burn or whether they are being debrided in theatre vs ED. Both recruitment and randomisation will be done by the primary investigator. Once the investigator has consented the patient, they will log onto the service, enter the stratification details and a participant ID and then the group allocation will be generated.
Blinding
Due to the nature of the study, double blinding will not be possible as both the treating clinicians and the participant will be aware of the treatment modality. Even if NPWT were to be applied to all participants but blinded to whether the intervention has been turned on, it is evident when looking at the dressing what treatment group the participant is in. It will be possible however to blind the clinicians to some of the secondary outcomes. Time to re-epithelialisation will be calculated based on when a blinded panel of clinicians deem photographs of the wound to be 95% re-epithelialised. Similarly, scar thickness will be measured based on three blinded ultrasound photographs. In addition, to minimize bias based on observation of wound re-epithelialisation, any surveys or questions regarding the patient’s progression will be asked of staff/patients before the dressings are removed.
Ancillary and post trial care
Standard post-acute follow up including routine PLCBC scar multi-disciplinary team follow up.
Outcomes
Pilot Trial Primary Outcomes
Previous acute paediatric burn RCTs have shown that theoretical frameworks for feasibility are often unachievable(27, 29–32). Given the specificity of the type of burn (significant hand and/or foot burns), it is likely that eligible participants will form a small subcohort. In addition, dropout rates may be higher for the 3 month follow up especially if there is no scar and the only reason to attend the appointment is for research purposes. Therefore for this study, a modified feasibility framework has been developed based on the guidelines of Polit & Beck(33)(Table 2). If at the completion of this trial, the results are inconclusive or have raised further questions, this study will help guide the feasibility parameters of a larger study.
Table 2
Study Feasibility Parameters
Nil minimum screening rate |
Greater than or equal to 80% of eligible participants will agree to enrol |
Greater than 80% of participants in the intervention groups will receive their allocated treatment (measured twice weekly while participant recruited to study) |
Less than 10% of data collection for primary outcomes will be missing |
Less than or equal to 40% of participants will be lost to follow up, withdraw from the study or be deemed ineligible after they have commenced treatment |
Intervention Primary Outcomes
Questionnaires will be administered to obtain qualitative and quantitative data regarding the feasibility, appropriateness and acceptability of staff, parents and participants using NPWT in acute paediatric hand and foot burns.
Staff questionnaire: A mixed method questionnaire incorporating Likert scales and open-ended questions will be developed using Weiner and colleagues model for implementation studies(34). The three criteria addressed are acceptability (is it ethically justifiable to use NPWT in paediatric hand and foot burns), appropriateness (the impact of NPWT on wound re-epithelialisation) and feasibility (is it physically possible to implement NPWT). This questionnaire will be asked at the start and end of the trial to see if the perception of NPWT has changed over the study period. In addition, feasibility of both current standard dressings vs NPWT will be asked in a combined Likert scale and open ended questionnaire at the point of the first dressing change to assess patient level data.
Participant questionnaire: A mixed method questionnaire incorporating Likert scales and open-ended questions will be administered assessing feasibility at the first dressing change. The questions will address the ease/difficulty and confidence of performing, maintaining, and adhering to the assigned dressing. This will allow an analysis of whether there is any perceived difference amongst patients between the dressings.
Safety/Harm will be classified based on the number and severity of adverse outcomes. The adverse outcome will be graded based on a modified Clavien-Dindo scale(35). This is an objective way to quantify the severity of an event from grade one, a deviation from intervention to grade five, death.
Adverse events will be recorded in an ‘Adverse Outcome Logbook’, stored in a locked cabinet at the Centre for Children’s Health Research. A grade will be given for each day the adverse event occurs. Parents of the participants will be provided with contact details for the burns centre to report any adverse events that may occur during the study. In addition to self-report, parents/participants will be questioned at each clinic appointment through the duration of wound care.
Secondary Outcomes
Percentage Re-epithelialisation: Clinical photographs will be taken at each dressing change. A panel of experienced burns clinicians will perform a blinded review of the photographs to assess the progress of re-epithelialisation. The burn will be considered healed when 95% re-epithelialised. This method has been used with success in previous studies with primary outcomes of time to re-epithelialisation(27, 36).
Pain and distress: will be assessed at home between dressing changes via parents and patients and during dressing changes in clinic via clinicians. Parents and patients will rate their pain based on an age-appropriate scale. Patients aged 3–8 years old will self-report pain intensity using the Faces Pain Scale Revised (FPS-R), a validated scale for paediatric pain assessment. The main benefit is that it demonstrates pain in a gender de-identified face whilst conforming to a linear interval scale that children can relate to(37). Participants over eight years old will self-report using the 11-point Pain Numerical Rating scale (P-NRS) (0 to 10). The P-NRS is validated for children > 8 and is easier to use than the FPS-R as it does not require an additional tool(38). For children of all ages, parents will report their perceived ranking of their child’s pain on an 11 point P-NRS (0 to 10). There is evidence to suggest good correlation between patient and parent assessment of pain and it is a useful surrogate when a participant score is not able to be ascertained(39).
Clinicians will assess the child’s pain and distress during dressing changes using the face, legs, activity, cry, consolability (FLACC) scale. This is a validated tool for clinicians to assess pain, with evidence suggesting that with experienced burns nurses (which account for the nursing staff at QCH) the accuracy increases(40). In addition, any analgesic and/or sedative medications administered to the participant at each dressing change will be recorded. This is given in accordance with the pain ladder, where burns that are likely to be larger will receive stronger medication.
Itch: Will be assessed by parents, participants and clinicians. Parents will rank the perceived itch for children under five years using The Toronto Paediatric Itch Scale – a validated, observation-based scale rating itch behaviours on a scale of 0 (absence of itch) to 4 (severe itch with significant disruption). It helps parents to accurately identify itch based on common paediatric itch patterns rather than the patient having to state they are itchy(41). Parents of children over five will rate their itch on an 11-point Itch Numeric rating scale (I-NRS) (0 to 10). Participants aged five to eight years of age will use the validated Itch Man Scale(42), asking patients to identify which picture on a 5 point scale (0–4) best represents their itch. For children over 8 years, a self-reported 11-point I-NRS (0 to 10) will be used. Clinicians will also be asked to rate the perceived itch on an 11-point I-NRS (0 to 10). The requirement for antipruritic medication will be recorded including the dose and number.
Scar/skin assessment (At 3 months): At 3 months following full re-epithelialisation of the burn injury, a face-to-face follow-up will be completed with all participants to conduct a skin and/or scar review. This time point was picked to assess the development of hypertrophic scar formation, requiring 2–3 months(13). No surgical interventions for scar management will take place between the time of re-epithelialisation and this appointment. Any garments, splints or silicone-based gels required in the interim will be recorded. An ultrasound scan, using BT12 Venue 40 MSK (GE Healthcare) will be taken to measure the thickness of the scar. This is a validated tool for measuring scar thickness and has been utilised in previous studies(43). Three central images of the scar will be taken (as opposed to peripherally on the scar border) to use in a blinded analysis by clinicians to confirm scar thickness. The Brisbane Burn Scar Impact Profile (BBSIP) will be used to measure the intensity and frequency of sensations such as pain, tightness and discomfort as well as health related QoL specific to burn scars. This tool is validated for measuring the health-related QoL in children with burn scars (32). Where a scar crosses a joint, range of motion will be assessed(19).
Cost Analysis: A record of the resources and associated cost (costed at market rate) for each participant will be recorded. This will include treatment costs (e.g. the number of dressing changes, type and size of dressings used, scar therapy products), as well as other burn-related resources (and costs) that may be important to a health service deciding which of the interventions to implement in their burn care model. Number of admissions, length of stay, number of operations and clinic appointments will be recorded and costed at hospital projections (ie price of hospital bed per night, hourly theatre rate). Labour time (e.g. occupational therapists, physiotherapist, nurses and surgeons) will be quantified for each patient (on the basis of time duration utilised and number of appointments required) and costed at the relevant state award rates for each respective discipline. This data will be recorded with each presentation to hospital.
Sample Size
This is a pilot study. It is primarily designed to determine whether NPWT is a feasible, acceptable and safe intervention in paediatric hand and foot burns given the apprehension of use in this cohort in our previous trial. This study is not powered to achieve statistical significance for secondary outcomes. This pilot study will enrol 30 participants to determine feasibility, safety and acceptability of the proposed intervention. With thirty participants it is projected that study feasibility will be established, providing an estimate for the requirements of a full RCT. There is minimal relevant literature to base expected outcomes on, sample size has therefore been based off the recommendations of Whitehead et al(44), Birkett and Day(45) and Browne(46).
Data collection methods
Data will be collected using REDCap (Vanderbilt, Tennessee, USA) database developed questionnaires to gather baseline demographic and clinical details (including mechanism, date, time of injury, time to presentation, vaccination status, medical/surgical history, Fitz-Patrick skin type) and assess pain, itch, feasibility, resource use and cost and scar development (Fig. 1). The E-Burn mobile application in combination with photographs will be used to accurately assess TBSA down to 0.1% which is particularly important given most burns will be small TBSAs(47). E-burn will be used as it is a validated app for TBSA assessment, reducing the risk of human error(48).
Burn depth will be categorized by laser doppler imager (LDI) scan and treating consultant review of photographs (taken using a Fujifilm x-T3 camera with a 60mm lens) at presentation and the first dressing change (between days 3–7) as either ‘superficial partial thickness only’, ‘mixed depth’, or ‘deep dermal partial thickness only’. The photograph review will be blinded.
Data management/Confidentiality
Each participant involved in the study will be de-identified and allocated a unique identifier. Data will be stored in a de-identified manner either online via REDCap and the Griffith Research Space or onsite in a locked cabinet at the Children’s Centre for Health Research.
Data Analysis
Continuous data will be summarised as either mean (standard deviation) or median (interquartile range) depending on distribution, while categorical data will be summarised as frequency (percentage). Data will be compared between-groups using linear regression (continuous outcomes), logistic regression (binary outcomes) or Poisson regression (count outcomes). In all cases treatment group will be included as a fixed effect in the analysis model. The assumptions for each model will be tested, and if model assumptions are not met comparisons will be made using non-parametric methods.
When the outcome variable is measured repeatedly, for example pain, we will use multilevel mixed effects models to account for the likely non-independent of the repeated measures from each participant. In these situations treatment group and time will be included as fixed effects, with a group-by-time interaction.
An intention-to-treat analysis is preferred as it compares all subjects in the groups to which they were originally randomly assigned (despite withdrawal, treatment failure or cross-over). However we will also conduct per protocol analyses to assess the potential effect of complying to treatment.
Trial Monitoring
The Human Research Ethics Committee will be contacted of any adverse events. In addition, a notification of any adverse outcomes to an external regulatory board comprised of burns clinicians independent of the trial will be completed to ensure nil modifications or trial cessation is required. Regular team meetings will be held where the principal investigators will review study progress, address pertinent issues and identify further actions to take. The principal investigators will ensure; via this regulatory review process, that data is managed appropriately (i.e. stored in a de-identified fashion) and that appropriate steps are taken with regard to data cleansing and dissemination of results.
Access to data
De-identified data will be available on request after appropriate ethics approval.
Patient and Public Involvement
This study was guided by previous patient experience of NPWT, identifying barriers and trying to optimise or better understand these barriers(27). The patients email address will be collected at recruitment so the results of the study may be disseminated to the participant.