The Effect of PDRN, an Adenosine Receptor A2A Agonist, on the Healing of Chronic Diabetic Foot Ulcers: Results of a Clinical Trial.

Context: Foot ulcer is the principal cause of hospitalization for patients with diabetes. Polydeoxyribonucleotide (PDRN), an adenosine A2A receptor agonist, improves wound healing in diabetic mice. Objective: The aim of this study was to evaluate the effect of PDRN on chronic ulcer healing in patients with diabetes. Design and Setting: This randomized, double-blind, placebo-controlled trial, involved two medical centers in Italy. Intervention: Patients with diabetes showing hard-to-heal ulcers (Wagner grade 1 or 2) were randomly assigned to receive placebo (n = 106) or PDRN (n = 110). The treatments (PDRN and placebo) were performed 3 days a week for 8 weeks by intramuscular and perilesional route. Main Outcome Measures: The primary outcome was complete ulcer healing. Secondary outcomes were the days needed to complete wound closure and the reepithelialization of wound surface (as percentage of the original area). Results: After 8 weeks, 91 placebo and 101 PDRN subjects completed the study. Complete healing was achieved in 18.9% [95% confidence interval (CI) 11.4-26.3] of placebo and in 37.3% (95% CI 28.2-46.3) of PDRN-treated patients (P = .0027). After 8 weeks, PDRN increased the closure of foot ulcers in diabetic subjects (hazard ratio 2.20; 95% CI 1.29-3.75; P = .004). The median time to complete wound healing was 49 days for placebo (range 28-56 d) and 30 days for PDRN-treated subjects (range 14-56 d; P = .0027). The median epithelialized area of the ulcers (expressed as percentage) was 49.3% in the placebo and 82.2% in the PDRN group (P < .001). Conclusions: PDRN facilitates the healing of Wagner 1 or 2 diabetic foot ulcers.