The effect of PDRN, an adenosine receptor A2A agonist, on the healing of chronic diabetic foot ulcers: results of a clinical trial.
BACKGROUND
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.


METHODS
This randomized, double-blind, placebo-controlled trial, involved two medical centers in Italy.


METHODS
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 for 8 weeks by intramuscular and perilesional route [corrected].


METHODS
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.
Departments of Clinical and Experimental Medicine (F.S., A.B., V.A., G.P., C.S., L.M., A.S., M.V., D.C.), Paediatric, Gynaecological, Microbiological, and Biomedical Sciences (D.A.), and Experimental Surgical Sciences and Dentistry (G.D.C.), University of Messina, 98125 Messina, Italy; Diabetology Unit (E.D.F.), Cardarelli Hospital, 80131 Naples, Italy; and Department of Internal Medicine (S.C.), University of Palermo, 90128 Palermo, Italy.
Francesco
F
Squadrito
Alessandra
A
Bitto
Domenica
D
Altavilla
Vincenzo
V
Arcoraci
Giovanni
G
De Caridi
Maria Eugenio
ME
De Feo
Salvatore
S
Corrao
Giovanni
G
Pallio
Carmelo
C
Sterrantino
Letteria
L
Minutoli
Antonino
A
Saitta
Mario
M
Vaccaro
Domenico
D
Cucinotta
D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017719:Diabetic Foot / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011089:Polydeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
D058908:Adenosine A2 Receptor Agonists; D011089:Polydeoxyribonucleotides