Wound exudate is crucial for wound healing, as it provides moisture, promotes cell migration, and delivers nutrients and growth factors (Peña and Martin, 2024), thus supporting the healing processes in acute wounds (Feng et al, 2024). It aids in autolytic debridement, removing dead tissue. However, excessive or insufficient exudate can delay healing, causing infection or desiccation. However, in the case of non-healing wounds where the processes of normal wound healing have been compromised (desJardins-Park et al, 2022), wound exudate can be responsible for tissue damage resulting in the delaying of healing (Pastar et al, 2023). For example, elevated levels of protein-degrading enzyme activity (e.g., matrix metalloproteinases [MMPs]), and changes in surface level pH in chronic wounds are detrimental to healing (Gethin, 2007; Caley et al, 2015). The consequences of excess non-healing wound exudate can lead to several additional clinically relevant consequences, including increased devitalised tissue in the wound bed (which can act as a nidus for infection), result in localised tissue maceration/excoriation, and lead to a significant reduction in patient quality of life (e.g., leading to detrimental social and psychological outcomes) (Goswami et al, 2020; Goto et al, 2020). Monitoring of exudate type and volume informs effective wound management (WUWHS, 2019).
Dressing selection is of key importance in wound management, particularly for the management of wound exudate (Britto et al, 2024). In wounds where exudate is an issue, a dressing should be chosen that will be effective in managing fluid and protecting the surrounding skin (Moore and Strapp, 2015). There are several different dressing types made of different materials and in different forms, each with their own advantages and disadvantages, and clinical applications (Bülbül et al, 2022; Britto et al, 2024).
ActivHeal® AquaFiber™ Extra (AAE) is a primary wound dressing, which is a blended alginate-CMC non-woven dressing. AAE a soft, conformable, highly absorbent dressing which turns into a soft, cohesive gel when in contact with wound exudate. It aids autolytic debridement and maintains a moist wound healing environment. This dressing is indicated for the management of a variety of moderate to heavily exuding wounds; for example, leg ulcers (venous and arterial), pressure ulcers, diabetic ulcers, superficial and partial-thickness burns, cavity wounds, graft/donor sites, postoperative surgical wounds, and traumatic wounds (e.g., lacerations, abrasions).
The aim of this non-comparative clinical evaluation of AAE was to provide real-world (Liu and Panagiotakos, 2022) clinical data and to evaluate the overall effectiveness of the dressing.
Materials and Methods
Study design and patients
This study was a prospective, open-label, single-arm, observational, multicentre clinical study at nine centres located throughout South Africa.
Any patient presenting with a venous or arterial leg ulcer, pressure ulcer, diabetic ulcers, lacerations and abrasions, postoperative surgical wound, donor sites, superficial and partial thickness burn, and cavity wounds with moderate to heavy levels of exudate, and that the investigator had decided to treat with a dressing designed for wounds with moderate to heavy exudate levels were eligible.
All diagnostic and therapeutic decisions were made by the treating physician. Each patient was treated according to the local clinical routine, and evaluated during a treatment period of a maximum of 6 weeks.
All clinicians involved in the evaluation were provided with information about the dressing, how it should be used, and received practice on how to use the dressing. Study site teams responsible for data collection and documentation were trained on how to complete provided study assessment forms.
Ethical approval and patient consent
This clinical study was conducted in accordance with national regulations concerning the conduct of clinical studies with medical devices. The study protocol was submitted to an independent research ethics committee (Pharma-Ethics, South Africa) and approved in April 2022 (ref no.: 220124498).
All patients meeting the inclusion criteria [Box 1] were informed of the purpose of the study, in addition to the processing of their personal and health data, and their explicit written consent was collected prior to inclusion. Patients were able to withdraw their consent to participate in the study.
Evaluated dressing
The evaluated dressing is a blended alginate-CMC non-woven dressing (ActivHeal® AquaFiber™ Extra) indicated for use in moderate to heavily exuding wounds. The dressing consists of an alginate and CMC core with an integrated Nylon reinforcing layer, providing additional tensile strength and integrity to the dressing without affecting the product performance. It allows for intact removal from cavity wounds and prevents dressing disintegration when used on particularly highly exuding wounds. As wound exudate is absorbed the alginate along with CMC forms a soft gel, which aids autolytic debridement, which is the natural breakdown of devitalised tissue by the body’s own enzymes (e.g., matrix metalloproteinases [MMPs]) in a moist environment, while also maintaining a moist environment for optimal wound healing.
Assessments and outcomes
The primary outcome of the evaluation was to assess the effectiveness of the blended alginate-CMC non-woven dressing as measured by wound progression parameters such as percentage reduction of devitalised tissue, and wound size and/or depth. Additionally, the safety of the dressings was assessed as a secondary outcome.
At the initial visit, patient data collected included the patient’s biological sex, age, wound aetiology, wound assessment of tissue type, wound size, pain levels (including analgesic pain usage), level of wound exudate and wound duration. Note that, for burn wounds, the cause of the burn wound (thermal, chemical, electrical, radiation) was noted. Burn wounds were assessed using the “rule of nines,” where the major body surface areas are divided into multiples of nine (Hettiaratchy and Papini, 2004).
At each follow-up visit (including the final visit at week 6), the investigators documented an assessment of the wound site (e.g., percentage wound type), wound progression, the change in wound area, maceration and skin condition, wound pain and pain experienced at dressing change, change in analgesic medication usage, an assessment of the clinician’s satisfaction in terms of conformability and application of the dressing, frequency of dressing change, and with regard to maintenance of a moist wound environment, exudate management, autolytic debridement and desloughing, conformability and ease of use. Wound progression was achieved if:
- the investigator observed complete healing (100% re-epithelialisation)
- the investigator determined that, if the wound was still present, there was an improvement in the wound (e.g., reduction in wound size (area and/or depth) or a reduction in the levels of necrotic or sloughy tissue in the wound).
- If the wound improved to the point where the level of exudate is less than what is indicated or advised by the investigator to continue use of the blended alginate-CMC non-woven dressing.
Wound area (cm²) was calculated using the formula: length (l) x width (w). Measurements were taken in each dimension at the widest extent of the wound. Wound depth (d) was measured in centimetres at the deepest part of the wound. Wound tissue type was assessed as a percentage of the total wound area to calculate the proportion of tissue types (necrotic, sloughy, granulation, and epithelial) present in the wound bed. Pain intensity associated with the wound was assessed in patients using a visual analogue scale (VAS, where 0=no pain and 10=worst possible pain). Level of clinical satisfaction with the device (conformability and ease of use) was assessed using a three-point Likert-type scale (‘very satisfactory’, ‘satisfactory’ and ‘not satisfactory’).
Adverse event data was collected at the study follow-up visit (days 35-47) and by assessing any additional admission and voluntary patient visits at any healthcare facility during the follow-up period. The relationship of the adverse events (AEs) with the evaluated dressing was also assessed.
Statistical analysis
Statistical analyses were performed according to the statistical analysis plan. Variables were reported as mean ± standard deviation, 1-sided 95% confidence interval (CI) (97.5% 2-sided CI), median, minimum and maximum, count or percentage. Parameter percentage reduction is calculated using the following formula: “100 – ((end visit value/baseline) x 100)”.
Results
The total number of 238 patients were enrolled in the study, 21 of which withdrew from participation in the study or were lost to follow-up resulting in 217 complete datasets. Each study subject was treated with one blended alginate-CMC non-woven dressing at each dressing change in accordance with the study protocol. A summary of patient demographics and baseline wound characteristics are presented in Tables 1 and 2, respectively. Of the patients who completed the study, 34.6% (n=75) of the wounds treated healed (100% epithelialisation), 17.5% (n=38) progressed to another therapy, and 32.3% (n=70) had the dressing disconinued at the study exit. A small number of wounds deteriorated (2.3%, n=5) to the point of requiring other therapy and one patient died, which was not device related. Eight (3.7%) patients discontinued early.
Baseline characteristics of patients
Patient demographics are summarised in Table 1. The treated cohort included 118 (54.4%) males and 99 (45.6%) females, aged between 10-99 years. Patients aged over 60 years represented the largest group of patients (n=98, 45.2%) with 91 (41.9%) patients aged >30-60 years. Twenty-seven (12.4%) patients were aged 18-30 years, and one patient was aged <18 years.
Baseline characteristics of included wounds
Wound characteristics are summarised in Table 2. Although cavity wounds represented the largest population of wounds included in this study (n=33, 15.2%), the proportion of wound types were similar, ranging in proportion between approximately 11-15% [Table 2]. Venous disease represented the largest aetiology for leg ulcers (n=23, 76.7%), and Category 3 was identified as the largest proportion of pressure ulcers (n=17, 58.6%). Neuropathy was the predominant aetiology in study patients with diabetic ulcers (n=19, 79.2%), and there were no diabetic ulcers of ischaemia-only aetiology. A thermal original was the major origin of patients with burn wounds (n=28, 90.3%), and partial-thickness burn wounds was the main burn wound type (n=27, 87.1%). Of the traumatic wounds included in this study, traumatic laceration wounds represented the largest group (n=18, 58.1%).
A mean wound-related pain intensity score of 4.8±3.05 was measured on the 10-point VAS scale, with individual pain intensity scores ranging from 0 (no pain) to 10 (worst pain possible) [Table 2].
Mean wound bed tissue types indicated that the wound bed was predominantly granulation tissue (64.7±38.79). Devitalised tissue (necrotic and/or sloughy tissue) was also present in most wounds. Mean necrotic tissue coverage of the wound bed in the patient group (n=217) was 5.2±18.91% (range, 0.0-100.0%), and mean sloughy tissue coverage was 25.2±34.33% (range, 0.0-100.0%) [Table 2].
Patients were screened for wounds with moderate or highly exuding wounds. Wounds with a moderate level of exudate production were the largest group (n=116, 76.5%), with the remaining 51 wounds (n=51, 23.5%) producing heavy levels of exudate.
Primary performance end-points
For this study, primary end-point success — wound progression from baseline to the end of the study — can be defined in several ways (see Assessments and Outcomes in Materials and Methods). Overall, there was a wound progression (including healing) achievement rate for the dressing of 96.3% (209/217).
Table 3 shows a summary of achievement of wound healing and/or progression for each of the wound types showing that there were good outcomes (>90%) across all wound types.
Wound size
By the final follow-up evaluation, 34.6% (n=75) of the wounds treated healed. Table 4 summarises the change in mean wound size (cm²) during the evaluation period for all wounds, and within each of the wound types. For all wounds, there was a significant change from baseline to end of study (75.8±394.1 cm² to 10.1±45.72, 86.7% reduction, P<0.0001), and for each wound type over the evaluation period [Table 4, Figure 1].
Reduction of wound bed devitalised tissue
As well as complete healing of the wound, or significant reduction in wound size as indicators of wound progression, if the wounds have not healed within the 6-week study period, a reduction in wound bed necrotic and/or sloughy tissue can also indicate successful treatment with the study dressing.
In terms of necrotic tissue, although there were changes noted in mean necrotic tissue levels for all individual wound types (except for post-op surgical wounds where there was no necrotic tissue identified) there was a significant change in mean percentage wound coverage for all wounds over the evaluation period (5.2±18.91% to 0.9±8.31%, 82.7% reduction, P<0.0001, Table 5, Figure 2). An absence of mean necrotic tissue coverage was observed in several wound types at the conclusion of the study evaluation period [Table 5].
For sloughy tissue, there was a significant change in mean percentage wound coverage for all wounds over the evaluation period (25.2±34.33% to 4.1±14.12%, 83.7% reduction, P0<0.0001, Table 6, Figure 3). Significant changes in mean percentage wound coverage of sloughy tissue in most individual wound types [Table 6] with changes in percentage coverage ranging from 72.2% to 99.4% [Figure 3].
Two cases are summarised in Boxes 2
and 3, with a summary of the wound characteristics, and images the wounds at baseline, intermediate, and final assessments.
Secondary performance end-points
Change in wound-related pain
As wound healing progressed, there was a significant change in wound pain intensity experienced (4.7±3.05 to 1.8±1.60, P<0001; n=216). Note that one patient did not have an end visit pain assessment, and this patient’s data was excluded as only subjects with both a baseline and end visit pain assessment are included in the analysis.
Level of satisfaction
Figure 4 shows the clinicians’ ratings of the level of satisfaction of the blended alginate-CMC non-woven dressing at the end of the evaluation. For most of the patients (>85%), the clinician rated the dressing as being ‘very satisfactory’ or ‘satisfactory’ for each of the product performance parameters assessed.
Safety
During the study period, no AEs related to the study device were documented.
Discussion
The results of the current post-market study indicate that AAE facilitates positive wound progression (including healing) outcomes in most patients, and that the majority of practitioners and patients in the clinical setting find the dressing ‘very satisfactory’ or ‘satisfactory’. AAE was used to manage various types of wounds, such as leg ulcers, diabetic ulcers, pressure ulcers, postoperative surgical wounds, and cavity wounds. It helped maintain a moist wound environment to promote wound healing and progression.
Wound size reduced over the study period (including a proportion of patients whose wounds heal within the 6-week evaluation period). All wound types showed a significant reduction in wound area during the study period, even when wound size at the outset of the study were large. For example, the baseline mean wound area for burn wounds was 341.1±980.1 cm² (range, 3.0-5400.0 cm²). Overall, treatment for 6 weeks with blended alginate-CMC non-woven dressing resulted in a reduction in wound size of between 52.5% (cavity wounds) and 97.4% (burn wounds), with a mean wound size reduction for all wounds of 86.7% [Figure 1]. A reduction in wound size was also observed in an evaluation of AAE in 43 patients with a variety of acute and non-healing wounds (Barrett et al, 2020). These wound size reduction trajectories compare favourably with results from clinical studies evaluating similar types of dressings. A recent meta-analysis observed the impact of moist wound dressings (including alginates, hydrocolloids, hydrofibers) on healing time and reported that the use of these dressings improved healing rates (e.g., promotion of reduction in wound size) (Liang et al, 2023). For example, a recent multicentre randomised control open-label trial in patients with hard-to-heal exuding wounds found that the use of a superabsorbent charcoal dressing found a significant reduction (P<0.02) in wound area (Probst et al, 2022). In a sub-analysis of a prospective observational study in patients with exuding wounds, Klein et al (2024) reported a significant reduction (P<0.05) in wound surface area when these wounds were treated with a gelling fibre primary dressing, and a 40% reduction in wound size was observed in a non-comparative evaluation of acute and non-healing wounds treated with a hydro-responsive wound dressing where these wounds requiring debridement (Hodgson et al, 2017).
There was an observed and significant reduction in the mean percentage of both necrotic [Table 5] and sloughy [Table 6] tissue by the final assessment in most acute and non-healing wound types where devitalised was present at the baseline assessment. A mean reduction of 82.7% was observed for wound bed necrotic tissue [Figure 2] and 83.7% for wound bed sloughy tissue [Figure 4]. Note also that, in the case of diabetic ulcers, graft/donor sites, trauma wounds, burn wounds, and cavity wounds, where necrotic tissue was observed, 100% of this devitalised tissue was observed to have been removed as a result of treatment with blended alginate-CMC non-woven dressing [Table 5]. The reduction in the levels of devitalised tissue (necrosis and sloughy tissue) during the evaluation period demonstrates that the dressing effectively aids with autolytic debridement. The literature indicates that autolytic debridement of devitalised tissue present in the wound bed is facilitated by the establishment of an optimal moist wound environment (Snyder et al, 2016; Mayer et al, 2024), and that this moist environment promotes wound healing (Nuutila and Eriksson, 2021). Autolytic debridement requires a moisture balance in the wound, a balance that is established by dressings such as AAE that creates a moist wound environment. The findings in this study are in line with the cleansing and debriding action of hydro-responsive wound dressings when used treating wounds with devitalised tissue (Ousey et al, 2021; Sterpione et al, 2021), and hydro-desloughing dressings that uses physical attraction of devitalised tissue within the wound’s moist environment to deslough the wound bed (Meaume et al, 2014).
The debriding properties of AAE (as seen in the reduction of both necrotic and sloughy tissue) suggest that this dressing may be used as part of an “integral debridement approach, “the combined use of different but complementary methods of debridement on the same wound” that offers a patient-centred, holistic approach (Mayer et al, 2024). In addition, the removal of devitalised tissue in this study compare favourably with other clinical studies using different debridement techniques (Nowak et al, 2022), and AAE can be used for desloughing alongside its exudate management capabilities. This study demonstrated that AAE facilitates positive healing outcomes in a variety of acute and non-healing wound types through the establishment of a moist wound environment. The positive wound progression findings of this study are also likely to be facilitated by minimal dressing-dependent tissue damage by AAE as a result of the gel-forming properties of AAE (Welch et al, 2017).
There was a corresponding reduction in wound pain intensity experienced by this study’s subjects. Wound progression results in a reduction in wound-derived pain as the inflammatory process of healing resolves (Holloway et al, 2024), as does the establishment of a moist wound environment (Nuutila and Eriksson, 2021). In this study, significant wound progression was observed in the study population across several wound types [Tables 3 and 4; Figure 1] indicating that AAE had no detrimental effect on wound healing. In addition, during the study period, no AEs related to the study device were documented, suggesting that there are no safety concerns with the use of AAE. the clinicians’ ratings of the level of satisfaction of the blended alginate-CMC non-woven dressing at the end of the evaluation. For most of the patients (>85%), the clinician rated the dressing as being ‘very satisfactory’ or ‘satisfactory’ for each of the product performance parameters assessed.
The findings from this evaluation highlight the clinical effectiveness of AAE across several clinical outcomes. Clinician-reported satisfaction levels indicate that AAE is well-suited for use in clinical settings for the treatment of indicated acute and non-healing wounds.
Conclusion
AAE facilitates wound progression, providing a moist wound environment and facilitating autolytic debridement for promoting an effective healing response and which, by optimising moisture levels in the wound, promotes autolytic debridement of devitalised wound tissue removing barriers to healing. Clinicians rated the dressing as satisfactory. AAE is effective in partnership with routine clinical practice for improving wound outcomes, particularly for reducing wound size and removal of devitalised tissue from the wound bed.
