A Prospective, Randomized, Double-Blind Multicenter Study Comparing Continuous Diffusion of Oxygen Therapy to Sham Therapy in the Treatment of Diabetic Foot Ulcers

Abstract

Background: Over the past generation, preclinical data have suggested that there is a potential physiologic benefit to applying oxygen topically to wounds. However, we are unaware of any studies in the literature that have robustly assessed whether this would lead to a higher proportion of healing in similarly treated people without oxygen. Therefore, the purpose of this study was to assess this in people being treated for chronic diabetic foot ulcers (DFUs).

Methods: We enrolled and randomized 100 subjects with DFUs (79% male, aged 58.3 ± 12.1 years) to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed until closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up.

Results: There were no significant differences in assessed descriptive characteristics between the treatment arms ( P > .05 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = .02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = .006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham ( P < .001).

Conclusions: The results of this study suggest that continuously diffused oxygen over a wound leads to significantly higher rates of closure, and faster time to closure, compared to similarly treated patients receiving standard therapy coupled with a sham device. Furthermore, the relative efficacy appears to improve the more the therapy may be needed (more chronic and larger wounds).

Keywords: closure rate; continuous diffusion of oxygen; diabetic foot ulcer; moist wound therapy; tissue oxygenation; wound healing.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MQN is a full-time employee of EO2 Concepts. DGA is a member of the Scientific Advisory Board of EO2 concepts.

Figures

Figure 1.

Consort diagram.

Figure 2.

Wound size at baseline by treatment arm and wound closure in all subjects (Active n = 50, Sham n = 50). The interaction between wound closure and wound size at baseline was not significant (P = .61). After removing the interaction term, the wound size at baseline did not vary significantly with treatment (P = .44), or wound closure (P = .11).

Figure 3.

Days to wound closure by treatment arm and wound closure (%) among subjects who experienced full closure (Active n = 23, Sham n = 11). The interaction of wound closure (%) and treatment was not significant (P = .75). After removing the interaction term, the treatment effect was significant (P = .026) and the wound closure (%) effect was significant (P < .001).

Figure 4.

Relative reduction in time to 50%, 75%, and full wound closure by treatment arm and wound closure among subjects who fully healed (Active n = 23, Sham n = 11).

Figure 5.

Full wound closure (%) by minimum baseline wound size and treatment arm. The effect of increasing the minimum wound size at randomization is shown. For example, 2.5 cm2 indicates all wounds between 2.5 and 10.0 cm2 at randomization were included in the sample. Samples sizes are indicated in parentheses.

Figure 6.

Relative performance versus minimum baseline wound size. The effect of increasing the minimum wound at randomization size is shown. For example, 2.5 cm2 indicates all wounds between 2.5 and 10.0 cm2 at randomization were included in the sample. Samples sizes are indicated in parentheses.