Comparing a Foam Composite to a Hydrocellular Foam Dressing in the Management of Venous Leg Ulcers: A Controlled Clinical Study
Venous leg ulcers are the most prevalent form of chronic wounds in the Western world, accounting for 45% to 60% of all chronic leg ulcers and occurring in 1% to 2% of people 65 years old and older in some countries.1
Most venous ulcers are not the result of external causes but arise from venous insufficiency that compromises return of venous blood to the heart. The clinical picture is characterized by alternating phases of ulceration and transitory healing. Despite recent advances in wound care, ulcers can take months to heal, have frequent complications (eg, infections and cellulitis), often recur, and are costly to treat.2 The refractory nature of venous leg ulcers can affect a patient’s quality of life and productivity at work, causing significant morbidity.3
Managing venous leg ulcers poses an enormous financial burden associated with diagnostic tests, nursing care, and rehabilitation. An estimated 2 million working days are lost per year in the US4 as a result of this condition. Although lower extremity ulcers are the most commonly occurring chronic wounds, many healthcare providers do not appreciate how to manage these wounds cost-effectively in an outpatient setting,5 and non-specialists in wound care are not always conversant with the information available on best practice.6
Currently, the standard of care consists of local wound management combined with compression bandaging to reduce edema and promote venous return.2 The principles of moist wound healing7-9 coupled with graduated compression bandaging10-12 have become the cornerstone of treatment for leg ulcers. Modern wound dressings have an increased capacity for managing exudate (and its potentially pathogenic bioburden), reducing the need for frequent dressing changes, protecting the surrounding skin, decreasing odor from wounds, and diminishing pain between and during dressing changes.
Dressings may differ in their ability to meet patient and caregiver needs. A recently developed foam composite (FC) dressing was designed to utilize the benefits of combining a hydrocolloid adhesive with a Hydrofiber® primary dressing covered with a foam secondary dressing. Non-comparative pilot research using this FC dressing13 for 5 weeks or up to 10 dressing changes resulted in marked improvement or healing of 82% of 11 leg ulcers with an average wear time approaching 5 days. Dressing changes produced little or no trauma and patients reported that discomfort did not occur or was negligible. Both hydrocellular foam (F) and FC dressings create a moist wound-healing environment, but their physical properties and construction differ. To date, no prospective randomized controlled trials have explored differences between the clinical performance of these two types of dressings. The purpose of this study was to compare the performance of these two foam dressings in the management of venous ulcers.
Materials and Methods
A prospective, stratified, randomized, comparative, multicenter study design was used to compare the two dressings at 15 sites in North America and Europe for a maximum study duration of 12 weeks. The sites included nine hospital outpatient or physician office-based clinics in the US, one physician office-based clinic and one hospital clinic in Germany, two community care agencies in the UK, and one physician office-based clinic each in Canada and France. Patients were randomly assigned to receive a protocol of care which included one of two foam primary dressings covered with a compression bandage.
Materials. Versiva® (ConvaTec, a Bristol-Myers Squibb company; Versiva is a registered trademark of E.R. Squibb & Sons, LLC, Princeton, NJ) is a sterile, adhesive, FC dressing with several layers: a perforated hydrocolloid adhesive layer facing the wound covered by a non-woven Hydrofiber® (Hydrofiber is a registered trademark of E.R. Squibb & Sons, LLC, Princeton, NJ) layer and a fluid-spreading layer of viscose and polyester covered by an outer polyurethane foam/film layer. Allevyn® Adhesive Hydrocellular Dressing (T. J. Smith and Nephew Limited, Hull, UK) is a waterproof adhesive F dressing.14 Both dressings are indicated to manage the exudate of a variety of chronic and acute wounds, including chronic ulcers resulting from venous insufficiency.
Inclusion and exclusion criteria. Patients were eligible for this study if they had a venous leg ulcer ≥2 cm2 but no larger than 11 cm x 15 cm, were clinically free of infection, and had an ankle-to-brachial systolic pressure index (ABPI) of ≥0.8. Patients with a qualifying venous ulcer who also had diabetes but were judged clinically to be under reasonable metabolic control (no history of hospitalization to manage glucose levels within the last 6 months) were able to participate. This criterion was selected rather than a more restrictive glycosylated hemoglobin diabetes criterion of HbA1C <9%, in order to maximize generalization of the study to a broad range of venous ulcer patients with diabetes. Patients were excluded if they had ulcers secondary to arterial disease, vasculitis, neoplasms, or hematological disorders based on prior diagnoses. Wound biopsies were not required within the study protocol. Also excluded were patients with a history of poor compliance with medical treatments, identified sensitivity to any of the dressings’ components, or an ankle circumference of <18 cm.
Appropriate IRB approvals and patients’ informed consent were obtained in accordance with the Helsinki Accord. Patients were randomized (1:1) to receive either FC or F. Before they were randomized, patients were stratified into two groups according to ulcer size (≤ or >10 cm2). Randomization to one of the two dressings was performed within each stratum.
Treatment. Ulcers were sharply debrided, if necessary, according to the usual practice of the 11 physician and four advanced practice nurse investigators before initial application of the study dressing or at any time during the study. The ulcer to be managed in the study protocol was photographed at enrollment and an acetate tracing was made. The study dressing was applied to the ulcer followed by the application of SurePress® High Compression Bandage (ConvaTec, a Bristol-Myers Squibb company; SurePress is a registered trademark of E.R. Squibb & Sons, LLC, Princeton, NJ). Wound or cavity fillers were not permitted unless severe maceration was observed following a wear time of less than 2 days, in which case AQUACEL® Hydrofiber® Wound Dressing (ConvaTec, a Bristol-Myers Squibb company; AQUACEL is a registered trademark of E.R. Squibb & Sons, LLC, Princeton, NJ) was used. An additional dressing retainer, Surgilast® (Western Medical, Inc., Summit, NJ), an elastic net tubular surgical stockinette, was used to prevent slippage of the compression bandage wrap between visits. Dressings were changed as clinically indicated according to manufacturer recommendations with a maximum wear time of 7 days. The treatment protocol continued for 12 weeks from enrollment or until healing of the ulcer, whichever came first. Follow-up occurred at least once every 7 days — more often if wound fluid leakage, indicated by the appearance of exudates strike-through on the compression bandage, occurred. To assess changes in ulcer size, acetate tracings were made at the first visit, every 14 days (± 2 days) thereafter, and at the final visit. Ulcers also were photographed at the first visit, after 6 weeks, and at the final visit. Both dressings were applied according to package insert instructions and used within the standardized study protocol of venous care, which included the high compression bandage and SurePress® Absorbent Padding (ConvaTec, a Bristol-Myers Squibb company; SurePress is a registered trademark of E.R. Squibb & Sons, LLC, Princeton, NJ) to ensure adequate sustained compression required for appropriate venous ulcer management, as well as topical agents for prophylaxis or for the treatment of pre-existing conditions of the periwound skin (eg, eczema). Wound fillers could be used with the F dressing but were not allowed with the FC dressing. End points measured dressing performance or investigator or patient satisfaction associated with the dressing differences in construction and physical properties.
Investigator-reported variables. At each dressing change, investigators recorded dressing leakage (1 = none, 2 = minimal, 3 = moderate, 4 = considerable, 5 = not applicable/dressing fell off); odor (1 = none, 2 = faint, 3 = moderate, 4 = strong, 5 = not applicable/dressing fell off); ease of removal ( 1 = very easy, 2 = moderately easy, 3 = not easy, 4 = not applicable/dressing fell off); dressing residue on surrounding skin (1 = none, 2 = minimal, 3 = moderate, 4 = heavy, 5 = not applicable/dressing fell off); trauma to wound bed and surrounding skin (1 = no trauma, 2 = trauma, 3 = not applicable/dressing fell off); and patient reported pain levels on the Johns Hopkins Pain Rating Instrument,15 both associated and not associated with dressing removal, as well as percent of the ulcer bed that was healthy granulation tissue, epithelial tissue, fibrin, slough, eschar/necrotic tissue, or other tissue on a 5-point scale.
At the final evaluation, overall investigator satisfaction with the dressing was rated on a 5-point scale (1 = excellent, 2 = very good, 3 = good, 4 = fair, 5 = poor) for each study participant according to: conformability, ability to soothe ulcer pain, exudate absorption (based on patient-reported dates and times of leakage), protection of the surrounding skin, non-sensitizing properties, non-traumatic dressing removal, ease of application, and ease of removal.
Patient-reported variables. Patient-reported measures included wound pain and date/time of dressing leakage. The latter was recorded in a patient diary, the former was evaluated using a visual analog scale (John Hopkins Pain Rating Instrument)15 at the initial evaluation and a final evaluation of the dressing’s effect on his/her pain (1= reduction in pain, 2 = increase in pain, 3 = no effect on pain, 4 = uncertain, 5 = unable to respond.)
Healing was assessed as the rate of complete healing by the end of the study (maximum 12 weeks), time to complete healing (difference between enrollment and healed date), and rate of healing (cm2 and percentage change) per week. Overall change in condition of the ulcer and surrounding skin was assessed on a 6-point scale (1 = healed, 2 = marked improvement, 3 = mild improvement, 4 = no change, 5 = mild deterioration, 6 = marked deterioration).
Dressing change frequency was assessed by calculating wear time (days) and number of dressing changes.
Statistical and data management. All data were verified by double-key entry as entered into a SAS® database and analyzed using Release 8.1 (TS1MO) of the SAS® System for Microsoft Windows (SAS Institute Inc., Cary, NC). All data were analyzed on an intent-to-treat basis, including all patients enrolled in the study, unless specified in the accompanying text on “evaluable” patients as defined by completing at least 9.6 weeks of the assigned dressing protocol. Demographic and baseline patient characteristics were analyzed using P-values based on least significant difference tests within corresponding Analyses of Variance (ANOVA) for quantitative data and by applying the Cochran-Mantel-Haenszel test for ordinal (ie, having a logical order) qualitative data. The rate of healing (cm2 and percent change per week) was analyzed using ANOVA. A logistic regression model was used to analyze the proportion of ulcers healed during the study. Survival analysis methods were used to analyze the time to complete healing, with survival curves for both dressing regimens compared using both the Log-rank test and the Wilcoxon test. The incidence and nature of adverse events that occurred during the study were summarized overall by patient and also by severity and relationship to study treatment. All statistical tests were evaluated at the alpha = 0.05 level of significance.
Participant demographic and ulcer characteristics. Of the 107 patients (FC group: n = 55; F group: n = 52) who were enrolled into the study, 31 (29%) withdrew before completing the 9.6 weeks required for inclusion in the analysis. Seventy-five (70%) of the ulcers were ≤10 cm2 in area (37 in the FC group and 38 in the F group). No statistically significant differences between dressing groups were noted in the percents of patients withdrawn or allocated to the stratified ulcer sizes, confirming that the analyses according to protocol on an intent-to-treat basis on all enrolled patients were appropriate and without bias.
Demographic and baseline characteristics of the enrolled patients are summarized in Table 1. No statistically significant differences between regimens were found except for patient age and duration of ulcer to be managed: patients in the FC group tended to be younger and have had ulcers for a longer period of time.
Safety. Thirteen patients (24%) experienced one or more possibly dressing-related adverse events for a total of 19 adverse events in the FC group, and 15 patients (29%) experienced a total of 18 possibly dressing-related adverse events in the F group. This was not statistically significant (P = 1.00; Fisher's Exact Test). The most common adverse event with FC was new wound development in different anatomical locations (six patients, 11%), followed by non-specific/other wound-related events such as events related to wounds on the same patient other than the wound enrolled in the study (five patients, 9%). In the F group, the most common adverse event was maceration, which affected six patients (11%), followed by non-specific/other wound-related events (eg, on non-study wounds — four patients, 8%), and new wound development in different anatomical locations (four patients, 8%).
While most adverse events were mild or moderate in intensity, four patients experienced one or more severe adverse events unrelated to the dressing regimen. One episode of angina, one non-specific musculoskeletal tissue event, and one fatal outcome affected three (5%) FC patients and an unspecified blood disease affected one (2%) F patient. In most instances, these events affected only one or two patients. However, potentially (ie, coded as “yes,” “probably,” or “unknown”) regimen-related events affecting more than two F patients were maceration (six patients, 11%) and non-specific/other wound-related events (four patients, 8%). Potentially regimen-related events affecting more than two FC patients were non-specific/other wound-related events (three patients, 5%) and new wound development in different anatomical locations (three patients, 5%).
Dressing changes and wear time. In the intent-to-treat population, patients in FC group were treated for an average of 58.6 (SD 28.3) days and dressings were changed an average of 11.4 (SD 6.5) times for an average wear time of 5.6 (SD 1.3) days. No significant difference was noted between this and the average treatment time of 52.8 (SD 26.3) days with an average 10.1 (SD 6.3) dressing changes or average wear time of 5.6 (SD 1.2) days for the F dressing.
Investigator-reported satisfaction. The level of satisfaction with the dressing is summarized in Figure 1 as the percent of patients for which the investigator reported the indicated level of satisfaction for each parameter studied. The FC dressing performed significantly better than the F in terms of conformability (P = 0.05); absence of sensitizing reactions (P = 0.02); and ease of application (P = 0.01). No statistically significant differences were noted between dressings in terms of exudate absorption, protection of surrounding skin, non-traumatic dressing removal, and ease of removal.
Wound evaluation at dressing change. Results for levels of ulcer odor before dressing removal, level of wound exudate, and condition of surrounding skin at the time of dressing changes are summarized in Table 2. The level of exudate reported at each dressing change was minimal or moderate in the majority of patients (79% for FC and 83% for F); reported maceration of the surrounding skin was similar in both groups (22% of FC dressing changes and 27% of F). Erythema, eczema, lipodermatosclerosis, cellulitis, and dermatitis were observed in similar percentages of dressing changes for FC and F groups.
Ulcer healing. No statistically significant differences were noted between the FC and F groups in terms of rate of healing (median FC: 0.41 and F: 0.43 cm2/week ; P = 0.13); percentage change per week (median FC: 7.3 %; F: 6.1 % ; P = 0.27); percentage of ulcers completely healed by study completion (FC 38.2%; F 38.5%; P = 0.96); or mean time to complete healing (FC: 66 ± 3.4 days; F 72.6 ± 3.1 days; P = 0.47). Patients in the FC group tended to have a longer mean duration of ulceration before study (3.3 ± 7.0 years) than F subjects (1.3 ± 2.3 years), but this did not result in any significant differences in healing between the FC and F groups.
Final overall assessment. Final overall evaluations for change in the condition of the ulcer, change in condition of the surrounding skin, and the patient’s description of the effect of the dressing on ulcer pain are summarized in Table 3. The surrounding skin had healed or shown marked improvement in 30 (54%) FC patients and 19 (36%) F patients; this difference was statistically significant (P = 0.03). By the end of the study, ulcers of 37 (67%) FC patients and 33 (63%) F patients had healed or shown marked improvement.
In the intent-to-treat population of patients responding in all categories, patient-reported effects of dressings on ulcer pain were not statistically different — 65.5% of patients reporting reduced pain in the FC group as compared to 42.9% in the F group. Conversely, 7.3% of FC patients reported that the dressing increased pain as compared to 18.4% of F patients (P = 0.10 for overall effect of dressing on patient-reported ulcer pain). These results showed a trend toward less pain with the FC regimen. Statistical significance might have been diminished because of the number of pain outcomes reported as “uncertain” and “no response.” To test for this possibility, a supplemental Cochran-Mantel-Haenszel test was conducted on the subset of 47 FC and 45 F patients who responded with certainty in the three categories of “decreased pain,” “no change,” or “increased pain.” The Cochran-Mantel-Haenszel test on this 92-patient subset found a significantly greater percentage of patients in the FC group than in the F group reporting a decrease in ulcer pain (P = 0.0075).
The significant differences between the FC and F dressings were more frequently observed investigator-rated improvement of skin surrounding the ulcer, satisfaction with dressing conformability, ease of application, and absence of sensitization in the FC than in the F group. Implications of these findings for clinical practice are improved skin condition surrounding the ulcer as well as improved ease of use for the FC dressing. Thus, both patient and caregiver benefit from the additional performance characteristics of the FC dressing.
The lack of ulcer healing differences was expected because FC and F dressings were applied within a standard protocol of venous ulcer care with sustained graduated high compression — both FC and F dressings provide the moist wound environment that supports an optimal healing environment for wounds.7-9,16-18 In addition, the use of elastic high-compression bandaging has been shown to be more effective in venous leg ulcer treatment protocols than non-compression bandaging.11,12,19
Maceration of the skin surrounding leg ulcers can occur due to excessive wound exudate, which can result in delayed healing and other complications, including scarring and skin stripping.20 The two dressings examined in this study are similar in their ability to absorb exudate, although they have been shown in vitro to differ in their capacity to retain a standardized amount of serum, with the FC dressing reducing wetness of the dressed surface for up to 120 hours after application.21 This difference in capacity to retain physiological fluids may help explain why only two of the eight regimen-related episodes of maceration were observed in FC patients, potentially contributing to their significantly greater improvement in the surrounding skin condition.
Another important consideration is potential exacerbation of the pain associated with leg ulcers caused by dressing changes. In a study of 65 patients with venous leg ulcers, 70% reported pain on entry into the study, with the affective nature of pain considered tiring and annoying.22 A general practitioner survey conducted in a number of countries reported that dressing removal was the most painful feature of the dressing regimen, especially if the dressing had adhered to the wound or if dressing removal had torn the skin.23 The ideal dressing must be able to be applied and removed easily without undue discomfort to the patient.24 Bandaging appears to improve pain and general quality of life to a greater extent than superficial venous surgery for venous leg ulcers patients, emphasizing the role of dressings in the care of leg ulcers.25 A new adhesive used in FC had the lowest peel force in a comparative study of adhesive dressings, although the experience of pain is not exclusively related to this attribute.26 In the present study, 12 of the 107 enrolled patients reporting “uncertain” and “no response” to pain limited an otherwise statistically significant difference in percentage of FC patients (65%) reporting a reduction in ulcer pain at the final study assessment as compared to F patients (43%). The implication of this result for future research is that improved methods of pain reporting and analysis are needed to identify bonda fide effects on patient-reported pain without having them masked by uncertain or non-responding individuals.
Dressing performance parameters are an important aspect of the regimen for managing venous leg ulcers. The FC dressing was significantly better than the F dressing in terms of level of satisfaction with conformability (87% and 75% of patients, respectively, scored this attribute “very good” to “excellent”); non-sensitizing (72.8% and 52% patients, respectively, scored this attribute “very good” to “excellent”); and ease of application (92.7% and 80.8% of patients, respectively scored “very good” to “excellent”). These factors have an impact on patient adherence to treatment regimen. Both dressings were well tolerated in this study and no unexpected adverse events were causally related to either dressing.
The results of this study are consistent with those of other studies using FC to manage venous leg ulcers.13,27,28 Comparable results were reported in a similar randomized controlled study28 comparing the performance of FC (n = 53) to that of a hydropolymer adhesive foam dressing (n = 48), Tielle® Plus (Johnson & Johnson, New Brunswick, NJ). The FC dressing performance exceeded (P <0.05) that of the hydropolymer adhesive foam dressing with respect to ease of dressing application and removal, non-traumatic dressing removal, and non-sensitizing nature of the dressing. Combined, these findings demonstrate that, compared to use of the two foam dressings (one studied here and one reported in the literature), using an FC dressing is consistently associated with a lower level of cutaneous sensitization and improved performance, such as ease of dressing application, non-traumatic dressing removal, and dressing conformability to ulcer wound surface. These factors all have the potential to improve clinical and patient quality-of-life outcomes. The consistent differential effects of F and FC dressings found in these study results merit further controlled research exploring the clinical and humanistic responses to a variety of wound care modalities.
The findings reported in this and other studies suggest that a FC dressing offers statistically significant improvements in condition of skin surrounding venous ulcers as well as dressing conformability, ease of application, and the capacity to be non-sensitizing. These factors may lead to improved quality of life for patients suffering from venous leg ulcers and for their caregivers.
The authors would like to thank the following clinicians for their contributions to this clinical study: Dr. William Ennis, Christ Hospital & Medical Center, Oak Lawn, Ill; Laurel Wiersema-Bryant, MSN, Barnes-Jewish Hospital, St Louis, Mo.; Dr. Tania Phillips, Boston University School of Medicine, Boston, Mass.; Susie Seaman, MSN, and Gwen Thomas, MSN,Wound Healing Center, Grossmont Hospital, La Mesa, Calif; Dr. Nanette Silverberg, Dermatology Associates of St. Luke’s-Roosevelt Hospital, New York, NY; Dr. Peter Sheehan, Hospital for Joint Diseases/OI, New York, NY; Dr. Julia Overstreet, Overstreet Health Center, Inc. Bellevue, Wash.; Dr. Alexander Reyzelman, San Francisco, Calif.; Dr. Marc Peauchault, Draveil, France; Dr. M. Baer, Hochenschwandt, Germany; Prof. Christian Meunter, Hamburg, Germany; Arthur Newton, Glasgow, Scotland; Sylvie Hampton, Eastbourne, UK.