Decellularized Dermis Allograft for the Treatment of Chronic Venous Leg Ulceration – the DAVE Randomized Clinical Trial

Objectives Venous leg ulceration (VLU) represents affects up to 1% of the population and 4% of the elderly. This condition results in significant impairment of patients’ quality of life, with physical effects including pain and reduced mobility, and psychological impact including social embarrassment and isolation. Despite receiving standard of care, which includes wound care, compression, and treatment of superficial venous incompetence, VLU healing represents a challenge with up to 30% unhealed after 6 months. Human decellularized dermis (DCD) allografts have been shown to be effective in randomized clinical trials in increasing healing rates of diabetic foot ulceration. The DAVE randomized clinical trial aimed to determine if DCD is an effective, safe, and cost-effective treatment adjunct for chronic VLU care. Methods This was a multicenter, prospective, randomized, open-label, pragmatic trial in the United Kingdom. Patients with chronic ulcers in the lower limb were assessed for enrollment into the study. Adults (≥18 years or older) who were able to provide informed consent, with a diagnosis of VLU, venous incompetence on ultrasound, an ankle brachial pressure index (ABPI) ≥0.8 and an index VLU present for at least 3 months and ≥2 cm2 in size were included. Patients were randomized to either the intervention (DCD graft and standard of care) or control arm (standard of care alone). Health-related quality of life was assessed using the EQ-5D and Charing Cross Venous Ulcer questionnaire. The analysis of the primary outcome (index ulcer healed at 12 weeks) was performed using mixed effects logistic regression. Results From October 2019 to October 2022, 71 participants (69.0% male; 68.0 ± 14.8 years) were recruited from 17 centers. Demographic and clinical characteristics at baseline were similar between groups. Median index ulcer area at baseline was 10.62 cm2 (interquartile range, 4.76-23.5). There were no differences in primary outcome (8.33% vs 14.3%; P = .455) and median healing times (164.5 vs 102 days; P = .780) observed between the intervention and control arms. The most common adverse events were wound or graft infection (n = 19), skin irritation and/or breakdown (n = 17), and pain (n = 15). There were 22 serious adverse events, but none were attributed to the application of DCD. Early termination of the trial was advised after interim data analysis due to a significantly lower rate of reaching the primary outcome (11.3%). Conclusions No differences in the primary outcome were observed between the intervention and control arms. The DAVE study has shown that DCD allograft is not an effective treatment adjunct in VLU care.

Citation

Tan, M., Balan, V., Onida, S., Heatley, F., Peerbux, S., Lee, R., Norrie, J., Lane, T., Epstein, D., Poskitt, K., Cullum, N., Chandrasekar, A., Lomas, R., & Davies, A. (2024). Decellularized Dermis Allograft for the Treatment of Chronic Venous Leg Ulceration – the DAVE Randomized Clinical Trial. Journal of Vascular Surgery: Venous and Lymphatic Disorders, 12(3). https://doi.org/10.1016/j.jvsv.2024.101753

DOI

10.1016/j.jvsv.2024.101753

URI

https://hdl.handle.net/20.500.14709/172

License

CC BY-NC-ND 4.0

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CC BY-NC-ND 4.0

License

https://creativecommons.org/licenses/by-nc-nd/4.0/