Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial

Abstract

Objectives: Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). Method: This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. Results: For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. Conclusion: This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

Molecular Biomarkers of Oxygen Therapy in Patients with Diabetic Foot Ulcers

“…The increased ROS levels appear to accelerate the signaling processes without causing any damage at the cellular level. On a clinical level, studies have shown comparable or decreased adverse events and hospitalizations compared to standard of care with no supplemental oxygen [38][39][40][41].…”

Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers

“…Partially conducted amid the coronavirus pandemic, this study had a 19% withdrawal rate. Nonetheless, this community-based study has demonstrated that TOT can lead to a statistically significant improvement in healing rates in patients with DFUs that are resistant to healing with optimal SOC alone [15].…”

“…CDO devices apply topical continuous diffusion of non-pressurized (normobaric) pure oxygen through small cannulas or thin tubes to semi-occlusive or proprietary wound dressings. Small portable, battery powered, electrochemical oxygen generators supply a continuous flow of pure oxygen over the wounds 24 h per day at a flow rate of up to 15 mL/h [13][14][15]. An oxygen gradient then develops between the overlying dressing and the wound bed, thereby facilitating oxygen diffusion.…”

“…These light-weight devices can be held in a small pouch affixed to the patient's leg or hip and allow for unrestricted ambulation within the prescribed offloading devices. There have been several recently published randomized controlled trials (RCT) that attest to their ease of use and positive effect on DFU wound healing [15][16][17][18].…”

“…Serena et al very recently reported on their multicenter RCT comparing another CDO device (Natrox) against good standard of care for the healing of chronic DFUs [15]. This 12 week study, open-label and unblinded, uniquely randomized 145 patients with chronic DFU to either SOC, using primarily a total contact cast (TCC), or to the active TOT group plus SOC/TCC.…”