Comparing Chitosan Sponge With Hydrocolloid as Dressing for Split-thickness Skin Graft Donor Site Wounds

Clinical Efficacy of Chitosan Sponge Compared With Conventional Hydrocolloid Dressing in Managing Skin Graft Donor Sites: A Clinical Trial

The goal of this clinical trial is to compare whether chitosan sponge have same clinical efficacy as a hydrocolloid dressing in treating skin graft donor site wounds. The main questions it aims to answer are:

Does chitosan sponge show comparable clinical efficacy as a split-thickness skin graft donor site dressing compared with a conventional hydrocolloid dressing?

Participants will:

The skin graft donor site wound will be divided into equal halves, and a chitosan sponge and hydrocolloid dressing will be applied to the same patient.

The rate of epithelialization will be assessed on days 10, 15, and 20 pain score, pruritus score, ease of removal, exudate level, and bleeding will be assessed on days 10, 15, and 20 The scar outcome will be assessed 2 months and 6 months post-procedure

Data Collection:

This is a prospective, single-blinded, comparative controlled-matched clinical trial involving patients in Hospital Pakar Sains Malaysia with partial thickness wounds created as a result of split-thickness skin graft harvest. Any patient requiring skin grafting and fulfilling the inclusion criteria will be approached preoperatively for recruitment in the study. Patients' donor site wounds will then be divided horizontally into two equal halves (superior and inferior) and dressed using chitosan sponge (Myplas® Sponge from Chitoplast Sdn. Bhd.) and hydrocolloid dressing (Elect Hydro™, Smith & Nephew) respectively, whereby the order for application of these 2 dressings will be randomised using https://www.randomizer.org/. The CONSORT statement for clinical trials is referred to during protocol development.

Patient consent:

Written informed consent will be obtained from all patients after counselling and understanding the information sheet given. For patients below 18 years of age, consent will be obtained from their legal guardian.

Sample size estimation:

Sample size was calculated using 2 dependent mean formulae from PS software. Total sample size with 10% drop out will be 22 patients.

Sampling method and subject recruitment:

Convenience sampling will be utilized for this study, whereby patient who requires STSG and fulfils inclusion and exclusion criteria will be enrolled for the study. Consent will be obtained from patients either in the clinic or ward before the commencement of the study and patient information sheets will be provided. Patient will be assessed on day 10, 15 and 20 after application of dressing either in ward or outpatient clinic. Subsequently patients will be assessed again in 2 months and 6 months post-application of the dressing in the outpatient clinic to assess the scar outcome. The total duration of participant involvement will be 6 months and the estimated time taken for evaluation during each clinic visit will be 5 minutes

Techniques of harvesting and application of dressing:

The graft harvested with dermatome either under local, regional, or general anaesthesia aiming to take uniform thickness of skin graft approximately 0.2-0.4mm and minimum wound size of 50cm2 . Hemostasis of the donor site was achieved with topical adrenaline (1:200,000). The donor site wound will be first cleaned with normal saline when it is due for dressing.

Donor site wound will then be divided horizontally into 2 equal half and dressed with both chitosan sponge and hydrocolloid dressing respectively with no buffer zone in between. The order for application of these 2 dressings will be randomized using https://www.randomizer.org/.

Applying 2 dressings over the same patient's donor site will also help reduce confounding factors among 2 different groups of patients if one type of dressing is applied to one patient. Furthermore, the decision to use 2 different dressings in the same patients was also due to the limited time available for the study and a limited number of patients.

Chitosan sponge will be secured with Hypofix as it is non-adherence. A secondary dressing with a special burn gauze is then applied for exudate management. The secondary dressing will be changed if soaked and the primary dressing will be changed if dressing is overwhelmed with moisture. Otherwise, it will be kept till day 10 with a concomitant wound inspection.

Statistical analysis:

All statistical analyses will be performed using R software version 4.3.1 in the RStudio environment. A significance level of p < 0.05 was considered statistically significant. Data will first assessed for completeness and accuracy. For numerical variables, the assumption of normality was evaluated using the Shapiro-Wilk test, histograms, and measures of skewness and kurtosis. Variables with non-normal distribution were analysed using non-parametric tests. Continuous variables were summarised as mean and standard deviation (SD) if normally distributed, or median and interquartile range (IQR) for non-normal data. Categorical variables were presented as frequency (n) and percentage (%).

Epithelialization percentage will be assessed at Day 10, Day 15, and Day 20. As normality assumptions were not met, Wilcoxon signed-rank tests were used to compare paired data between the chitosan sponge and hydrocolloid dressing at each time point. Results will be reported as median, IQR, median difference, 95% confidence interval (CI), and associated p-value. Graphical comparisons will be visualised using boxplots and jitter plots, with overlay of statistical annotations and bootstrap-estimated confidence intervals for the median difference.

Pain and pruritus scores will be recorded using the Visual Analogue Scale (VAS) at Days 10, 15, and 20. Due to non-normal distributions, Wilcoxon signed-rank tests will be used for within-subject comparisons. Results were presented using median (IQR), median differences, 95% CI, and p-values, along with corresponding boxplots. Ease of dressing removal will be assessed using ratings of "Very Good", "Good", "Neutral" or "Unpleasant" and will be analysed using the Stuart-Maxwell test for marginal homogeneity to assess differences in paired categorical outcomes. A heatmap will be used to visualise the paired responses across dressings. Exudate and active bleeding scores will be measured using the verbal rating scale (1= no event, 10 = maximum expression of event). The comparisons will be made using the Wilcoxon signed-rank test and reported using medians, IQRs, and paired difference summaries. Results will be visualised using grouped boxplots for clarity.

Scar quality will be assessed at 2 and 6 months post-operatively using the Patient and Observer Scar Assessment Scale (POSAS). Paired comparisons between dressings will be performed separately for patient-reported and observer-assessed scores using the Wilcoxon signed-rank test, due to the ordinal and non-parametric nature of the data. Outcomes will be summarised using median (IQR), median of difference, 95% CI, and p-values.

Ethical Consideration:

The privacy and confidentiality of the patients are respected. This study will be conducted in compliance with ethical principles outlined in the Declaration of Helsinki, Malaysian Good Clinical Practice (GCP) guidelines, and National Research Committee, Medical Research and Ethnics Committee (MREC) and Institutional Review Board.

Privacy and confidentiality:

1. All medical information is kept confidential and will not be made publicly available unless disclosure is required by law.
2. Data obtained from this study does not identify the patient individually thus may be published for knowledge-sharing purposes.
3. The original medical records may be reviewed by the researchers involved, the Ethical Review Board for this study and regulatory authorities for the purposes of verifying clinical trial procedures and/or data.
4. All medical information may be held and processed on a computer.

Vulnerability and Risks:

The expected adverse effects are low, given external application only. The human studies so far which was done reported no adverse effects. Allergy reactions like rash, and itchiness towards the dressing applied may occur. If there is any local irritation or reaction, the study will be halted and adverse reactions will be recorded. Appropriate treatment for the adverse reaction will be offered to the patient. Subjects will be given the full freedom to participate or withdraw from the research study without affecting his or her medical condition, management and care. The data collected will be independent and will not be disclosed to any parties to be used for any achievement assessment and decisions related to work.

Operational definition:

i. Clinical efficacy:

- ability of an intervention or drug to produce a desired effect in expert hands and under ideal circumstances.

ii. Healthcare worker:

• Nurses and plastic surgery doctor iii. Scar outcome score:
• Outcome of scar as determined by using POSAS version 3.

Inclusion Criteria:

• All patients with partial thickness wounds after split thickness skin graft harvesting
• Skin graft donors > 50cm2 wide
• Age > 12 years old
• Consented patients
• Patients compliant to the treatment protocol

Exclusion Criteria:

• Non-compliant patient, causing dressing to dislodge
• Patient with history of allergy to seafood
• Pregnancy