Decellularised Dermis Allograft for the Treatment of Chronic Venous Leg Ulceration – the DAVE Randomised Clinical Trial

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 six months. Human decellularized dermis (DCD) allografts have been shown to be effective in randomised clinical trials in increasing healing rates of diabetic foot ulceration. The DAVE randomised clinical trial aimed to determine if DCD is an effective, safe, and cost-effective treatment adjunct for chronic VLU care.

Methods:

This was a multicentre, prospective, randomised, open-label, pragmatic trial in the United Kingdom. Patients with chronic ulcers in the lower limb were assessed for enrolment 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 ABPI ≥ 0.8 and an index VLU present for at least 3 months and ≥ 2 cm² in size were included. Patients were randomised to either the intervention (DCD graft and standard of care) or control arm (standard of care alone). Health-related quality of life were 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 centres. Demographic and clinical characteristics at baseline were similar between groups. Median index ulcer area at baseline was 10.62cm² (IQR 4.76 to 23.5). There were no differences in primary outcome (8.33% versus 14.3%, p = 0.455) and median healing times (164.5 versus 102 days, p = 0.780) 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.