Multinational, Multicenter, Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen Therapy (TWO2) in the Treatment of Chronic Diabetic Foot Ulcers

Non-healing DFUs lead to increased mortality, morbidity and health economic burden. Our RCT (NCT02326337) was undertaken to explore the efficacy of Topical Wound Oxygen (TWO2) homecare therapy in healing DFUs that had failed to heal with Standard of Care (SOC) alone. A Group Sequential Design was utilized with 2 interim analyses, requiring a significance of p<0.022 at each. All subjects meeting the incl/excl criteria were enrolled into a run-in of SOC that included gold-standard offloading and sharp debridement. Only DFUs not on a proven healing trajectory with SOC alone (<30% wound area reduction) were randomized into the active phase of the study, where they were assigned (double blind) to either active, or sham (placebo), TWO2 device treatment arms. The primary endpoint of the study was ulcers healed at 12 weeks. At the first interim analysis point of 73 subjects, the active TWO2 arm was shown to be significantly superior to the sham arm (Pearson Chi² =7.2707, P=0.007). Multivariable analysis using logistic regression and Cox proportional hazards modelling of the secondary outcome measure of time to heal showed no other covariates achieved significance. The active TWO2 arm showed nearly 4 times the likelihood to heal DFUs in 12 weeks compared to the sham arm HR 3.88 (95% CI 1.40 to 10.71), p=0.009.