A Multi-Center, Multi-National, Prospective, Randomized, Double-Blinded, Placebo Controlled Trial Comparing Adjunctive Cycling Topical Wound Oxygen Therapy to Gold Standard Wound Care in the Treatment of Diabetic Foot Ulcers

Aim: Non-healing DFUs lead to increased mortality and morbidity.(a) Our rigorous multinational RCT protocol was designed to explore the efficacy of a unique Cyclical Pressurized Topical Oxygen (CPO2) therapy in healing refractory DFUs.(b) 

Method: A Group-Sequential-Design was utilized with 2 predetermined interim analyses requiring a p<0.022 at each. All subjects meeting enrollment criteria entered a 2 week run-in with optimal standard of care. Only DFUs achieving <30% wound area reduction were randomized (double blind) to either active, or sham, CPO2 device treatment arms.(c) The primary endpoint of the study was 100% ulcer healing at 12 weeks. All analyses were exclusively of the Intent-to-Treat population. Secondary endpoints included ulcer re-occurrence after 12 months and wound healing trajectories.

Results: At the first interim analysis point of 73 subjects, the active CPO2 arm was shown to be significantly superior to the sham arm (Pearson Chi2=7.2707, P=0.007). The active CPO2 arm showed nearly 4 times the likelihood to heal DFU in 12 weeks [HR 3.88 (95% CI 1.40 to 10.71), p=0.009]. Multivariate analysis showed that no covariates other than treatment achieved significance. At 12 months follow-up the ulcer re-occurrence rate was  6.7% in the active CPO2 arm and 40% in the sham  arm. Larger active CPO2 arm wounds that had not fully healed at 12 weeks showed a mean reduction in size of 64% compared to sham arm treated ulcers that showed a mean increase in size of 2% (P = 0.0052). 34 DFUs (23%) failed the run-in with ≥30% wound-area-reduction in 2 weeks.

Conclusion: This robustly designed double blinded placebo controlled RCT clearly demonstrates cyclical pressurized oxygen therapy to be significantly superior in healing recalcitrant DFUs than gold standard care alone. Additionally, cyclical pressurized oxygen therapy healed ulcers demonstrated a six times lower than normal re-occurrence rate at 12 months follow-up.(d)