Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes-ProNOx1 study

摘要

The aim of this multicenter, prospective, observer-blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting "real world" clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25-2,500 mm(2) and either a palpable pedal pulse or ankle brachial pressure index 0.5. Infected ulcers were included. Treatment lasted 12 weeks, or until healed, with a 12-week follow-up period. Both arms were given optimal debridement, offloading and antimicrobial treatment, the only difference being the fixed used of EDX110 as the wound dressing in the EDX110 group. 135 participants were recruited with 148 ulcers (EDX110-75; Control-73), 30% of which were clinically infected at baseline. EDX110 achieved its primary endpoint by attaining a median Percentage Area Reduction of 88.6% compared to 46.9% for the control group (p = 0.016) at 12 weeks in the intention-to-treat population. There was no significant difference between wound size reduction achieved by EDX110 after 4 weeks and the wound size reduction achieved in the control group after 12 weeks. EDX110 was well tolerated. Thirty serious adverse events were reported (12 in the EDX110 group, of which 4 were related to the ulcer; 18 in the control group, of which 10 were related and 1 possibly related to the ulcer), with significant reduction in serious adverse events related to the ulcer in EDX group. There was no significant difference in adverse events. This study, in a real world clinical foot ulcer population, demonstrates the ability of EDX110 to improve healing, as measured by significantly reducing the ulcer area, compared to current best clinical practice.