Longitudinal Evaluation of Biomarkers in Wound Fluids from Venous Leg Ulcers and Split-thickness Skin Graft Donor Site Wounds Treated with a Protease-modulating Wound Dressing.

Venous leg ulcers represent a clinical challenge and impair the quality of life of patients. This study examines impaired wound healing in venous leg ulcers at the molecular level. Protein expression patterns for biomarkers were analysed in venous leg ulcer wound fluids from 57 patients treated with a protease-modulating polyacrylate wound dressing for 12 weeks, and compared with exudates from 10 acute split-thickness wounds. Wound healing improved in the venous leg ulcer wounds: 61.4% of the 57 patients with venous leg ulcer achieved a relative wound area reduction of ≥ 40%, and 50.9% of the total 57 patients achieved a relative wound area reduction of ≥ 60%. Within the first 14 days, abundances of S100A8, S100A9, neutrophil elastase, matrix metalloproteinase-2, and fibronectin in venous leg ulcer exudates decreased significantly and remained stable, yet higher than in acute wounds. Interleukin-1ß, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) α1 abundance was higher in venous leg ulcer wound fluids and was not significantly regulated. Overall, significant biomarker changes occurred in the first 14 days before a clinically robust healing response in the venous leg ulcer cohort.

Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm2 . Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm2 at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.

Clinical performance and quality of life impact of an absorbent bacteria-binding foam dressing.

The aim of this prospective multicentre observational study was to assess the clinical performance and safety of Cutimed® Siltec® Sorbact® absorbent bacteria-binding foam dressing in wound healing and its impact on patients' quality of life (QoL). The study was conducted under routine clinical conditions in 5 study sites in Germany and Poland. Each patient with a venous leg ulcer (VLU) or a diabetic foot ulcer (DFU) was observed for 28 days (initial visit and close-out visit, as well as 3 control visits). An assessment of QoL of the patient was undertaken before and after the study. Sixty-two patients were included in the statistical analysis. Clinicians rated the following assessment parameters in relation to Cutimed Siltec Sorbact dressings as 'very good' to 'good': wearing comfort (rated by the patient), application and removal, exudate absorption with or without compression and fluid retention capacity with or without compression and infection management. The use of Cutimed Siltec Sorbact dressing was beneficial in absorbing wound exudate (chi-square=28.45, P value<0.001), reduction of the viscosity of wound exudate (chi-square=25.63, P value<0.001), and there were more intact, less macerated, red and oedematous wound surroundings. There was also a 9% decrease in the number of infected wounds at the close-out visit. Analysis of the Wound-QoL measures demonstrated a reduction in the perception of performance parameters associated with wound infection. It can therefore be deduced that the use of Cutimed Siltec Sorbact was effective in wound management and had positive implications for patients' QoL.

Clinical assessment of a foam dressing containing growth factor-enhancing hydrated polyurethanes.

OBJECTIVE: This study assesses a novel dressing concept in venous leg ulcer (VLU) patients. It is based on boosting endogenous growth factor activities synthesised by functional granulation tissue. METHODS: Patients received treatment for eight weeks with a hydrated polyurethane-containing foam dressing plus concomitant compression therapy. Wound area reduction (WAR), percentage of wounds achieving a relative WAR of ≥40% and ≥60%, wound pain ratings for the last 24 hours and at dressing changes, EQ-5D Quality of Life questionnaire data, dressing handling and safety parameters were recorded. RESULTS: There were 128 patients who received treatment and data for 123 wound treatment courses were documented. Wound area size decreased from 13.3±9.8cm2 to 10.5±12.2cm2 at week eight and median relative WAR was 48.8%. At week eight, a relative WAR ≥40% was reached by 54.5% of the wounds, 41.5% reached a relative WAR of ≥60% and complete healing was observed in 13.5% of wounds. Median wound pain ratings (last 24 hours before dressing change) declined significantly from 30 to 15.5 (100 visual analogue scale [VAS], p=0.0001) and pain at dressing changes from 30 to 12.5 (p≤0.0001). The EQ-5D VAS rating increased from 58.4±19.2mm to 63.1±19.1mm (p=0.0059). CONCLUSION: This clinical assessment shows that the concept of boosting endogenous growth factors through hydrated polyurethanes has the potential to accelerate WAR in VLU patients while decreasing pain levels and improving quality of life parameters.

Safety and performance evaluation of a next-generation antimicrobial dressing in patients with chronic venous leg ulcers.

The objective of this study was to investigate the safety and performance of AQUACEL™ Ag+ dressing, a wound dressing containing a combination of anti-biofilm and antimicrobial agents, in the management of chronic wounds. Patients (n = 42) with venous leg ulcers exhibiting signs of clinical infection were treated for 4 weeks with AQUACEL™ Ag+ dressing, followed by management with AQUACEL™ wound dressings for 4 weeks. Wound progression, wound size, ulcer pain and clinical evolution of the wound were assessed for up to 8 weeks. Adverse events were recorded throughout the study. AQUACEL™ Ag+ dressing had an acceptable safety profile, with only one patient discontinuing from the study, because of a non-treatment-related adverse event. After 8 weeks, substantial wound improvements were observed: 5 patients (11·9%) had healed ulcers and 32 patients (76·2%) showed improvement in ulcer condition. The mean ulcer size had reduced by 54·5%. Patients reported less pain as the study progressed. Notable improvements were observed in patients with ulcers that were considered to require treatment with systemic antibiotics or topical antimicrobials at baseline (n = 10), with a mean 70·2% reduction in wound area. These data indicate that AQUACEL™ Ag+ dressing has an acceptable safety profile in the management of venous leg ulcers that may be impeded by biofilm.

A prospective, multi-centre, randomised, open label, parallel, comparative study to evaluate effects of AQUACEL® Ag and Urgotul® Silver dressing on healing of chronic venous leg ulcers.

This study compared wound healing efficacy of two silver dressings, AQUACEL(®) Ag and Urgotul(®) Silver, against venous ulcers at risk of infection, over 8 weeks of treatment. The primary objective was to show non inferiority of AQUACEL(®) Ag to Urgotul(®) Silver. Patients (281) were randomised into two groups. The AQUACEL(®) Ag group had 145 patients treated with AQUACEL(®) Ag for 4 weeks followed by AQUACEL for another 4 weeks. TheUrgotul(®) Silver group had 136 patients treated with Urgotul(®) Silver for 4 weeks followed by Urgotul(®) for another 4 weeks. In both groups, ulcer size and depth, safety events and ulcer healing were compared. After 8 weeks of treatment, the AQUACEL(®) Ag group had a relative wound size reduction (49·65% ± 52·53%) compared with the Urgotul(®) Silver group (42·81% ± 60·0%). The non inferiority of the AQUACEL(®) Ag group to the Urgotul(®) Silver group was established based on the difference between them (6·84% ± 56·3%, 95% confidence interval -6·56 to 20·2) and the pre-defined non inferiority margin (-15%). Composite wound healing analysis showed that the AQUACEL(®) Ag group had statistically higher percentage of subjects with better wound progression (66·9% versus 51·9%, P = 0·0108). In general, both dressings were effective at promoting healing of venous ulcers.