The clinical and histological effects of Dermagraft® in the healing of chronic venous leg ulcers

Abstract

Objective: Pilot study to assess the safety and effectiveness of Dermagraft® when used in conjunction with multi-layer compression bandage therapy (Profore™) compared with multilayer compression only in the treatment of chronic venous leg ulcers. Design: Open-label, prospective, multicentre, randomized, controlled clinical trial. Methods: Patients aged at least 18 years with leg ulceration of venous aetiology were screened for inclusion in the trial. Patients with arterial disease (ankle brachial pressure index <0.7) and causes of ulceration other than venous disease were excluded. Patients were randomized into four groups. Three active treatment groups received Dermagraft® in combination with compression bandaging, Profore™: Group 1, 12 pieces of Dermagraft (one per week for 12 weeks); Group 2, four pieces of Dermagraft (Weeks 0, 1, 4, 8); Group 3, one piece of Dermagraft (Week 0). The control group was treated with compression bandaging alone (Group 4). The study was not powered to detect statistical differences in healing rates. Adverse events were reported according to national guidelines. There was no statistical analysis of adverse event data. Results: In all 53 patients were randomized, of whom 47 completed the study per protocol. At 12 weeks complete healing of the ulcer, analysed by 'intention-to-treat' (ITT) was 15% using Profore alone, 7% using single application Dermagraft and Profore (Group 3), compared with 38% using multiple applications of Dermagraft and Profore (Groups 1 and 2). At study discontinuation, the median percentage reduction in wound area was 81.4% for Group 1, 88.6% for Group 2, 59.4% for Group 3 and 78.1% for Group 4. No major safety issues were identified during the course of the study. Conclusions: The results of the pilot study indicate that four pieces of Dermagraft are the optimal application frequency to take forward to further clinical trials. Further studies are required to confirm these data, and these should be powered to detect whether there are statistical differences in healing rates and safety between different regimens.

Cost-Effectiveness of Three Adjunct Cellular/Tissue-Derived Products Used in the Management of Chronic Venous Leg Ulcers

“…Fifty-one articles were retrieved and reviewed in full with 41 rejected on full review. Of the 10 studies that met the inclusion criteria, 5 were used to populate the clinical outcomes of the Markov model [19,20,[33][34][35] and the remaining 5 were used to supply information on health economic, resource utilization, and ulcer recurrence [10,[36][37][38][39]. Where possible, resource utilization data were extracted from the clinical literature.…”

“…Of the four clinical trials [20,[33][34][35], three reported clinical outcomes of ulcer healing at 12 weeks [20,34,35], with one trial having outcomes up to 6 months [33]. The BoxMuller transform method was used to generate random number sampling from the reported means and SDs of the clinical trials [40].…”

“…ECM had the largest baseline wound surface area (10.2 Ϯ 1.5 cm 2 ), and HSE had the smallest baseline wound surface area (1.3 Ϯ 2.7 cm 2 ). The average wound duration at baseline ranged from 1.5 months to 2 years for all trials [20,[33][34][35].…”

“…The incidence of healing was similar in the standard care arms: 34% in ECM, 49% in HSE, and 12% and 15% for the LSE trials, respectively. Wound duration at baseline ranged from 2 months to longer than 2 years for all trials [20,[33][34][35]. Because wound characteristics were not statistically different, patients from the standard care arm in Mostow et al [20] were selected as a reference.…”

“…To extrapolate outcomes to 1 year, it was assumed that healing rates should be similar among CTPs after 12 weeks, and thus, in this study, the data from the venUS I trial [19] (specifically from the four-layer bandage standard care arm) were adopted to extrapolate healing trajectories beyond 12 weeks for the standard care, ECM, and LSE cohorts [20,34,35] and beyond 6 months for the HSE cohort [33]. Based on an analysis of wound trajectory data from the venUS I trial [19], probabilities of healing were simplified by calculating them for 12-and 26-week periods for each of the four comparative therapies assessed with the Markov model.…”