Effect of amelogenin extracellular matrix protein and compression on hard-to-heal venous leg ulcers

OBJECTIVE:To compare hard-to-heal venous leg ulcers treated with compression therapy alone versus compression therapy with amelogenin protein. Parameters used were: percentage reduction in wound size, number of improved ulcers, pain related to the disease and at dressing changes, amount and nature of exudate, and the safety and tolerability of the two treatments. METHOD:This was an open randomised comparative parallel group multicentre investigation with a three-week run-in period. Inclusion criteria included adult, mobile patients with hard-to-heal venous leg ulcers that had been treated with compression therapy for at least one month prior to screening. The ulcers had to be at least six months old, with a surface area at inclusion of 10-30cm2, and not demonstrating excessive exudate or signs of infection. At the end of the run-in period, additional criteria for eligibility, such as change in wound area of +/- > or = 50% and a wound area between 8cm2 and 36cm2 were applied. Patients were randomised to treatment with amelogenin plus high compression bandaging or high compression bandaging alone. All participants received high compression bandaging therapy one month prior to and during the three-week run-in period, as well as throughout the 12 weeks of active treatment. RESULTS:Eighty-three patients were randomised and received treatment: 42 with high compression plus amelogenin (amelogenin group) and 41 to high compression therapy alone (control group). The amelogenin group had a greater percentage reduction in ulcer size (mean - 33.1%) compared with the control group (mean - 11.07%) from baseline to the last visit (p = 0.06). The number of improved ulcers was significantly greater (p = 0.01) in the amelogenin group than in the control group. Compensating for baseline characteristics by multiple regression resulted in a statistically significant (p = 0.03) larger reduction in change in ulcer size in the amelogenin group. Statistically significant differences in favour of the amelogenin group were also found for reduction in ulcer-related pain (p = 0.01), reduction in pain at dressing changes (p = 0.02) and the proportion of patients with 'none' or 'low' levels of exudate (p = 0.01). CONCLUSION:The combination of amelogenin with high compression promotes the healing process in hard-to-heal ulcers. Application of amelogenin as an adjunct to compression results in a significant reduction in ulcer size, improvement in the state of ulcers, reduced pain and a larger proportion of ulcers with low levels of exudate. The results of this study are statistically and clinically significant