Successful Treatment of Moderately Ischaemic DFUs Using Intermittent Topical Oxygen
Summary: Published December 17, 2025 in the Diabetic Foot Journal (DiabetesontheNet), this article reports a post hoc analysis of a randomised, prospective, double-blind, sham-controlled study evaluating TWO2 — a cyclical pressurised topical oxygen therapy device — specifically in patients with moderately ischaemic diabetic foot ulcers (DFUs). This patient subset is clinically challenging because ischaemia restricts oxygen delivery to the wound bed, impairs cellular proliferation and angiogenesis, and substantially reduces response to standard care. Patients were adults with full-thickness, nonhealing DFUs (1–20 cm² post-debridement; University of Texas grade 1 or 2) present for 4 weeks to 1 year and failing at least 4 weeks of standard care. Moderate ischaemia was defined per IWGDF criteria as any of the following: ABI ≥ 0.7, TBI < 0.75, monophasic or biphasic Doppler waveforms below the knee, TcPO₂ < 60 mmHg, great toe pressure < 60 mmHg, or skin perfusion pressure < 60 mmHg. Following a 2-week run-in period, patients who had not responded were randomised to either an active TWO2 device or an identical-appearing sham device; all received standard foam dressings, below-knee off-loading (equivalent to total contact casting), and optimal standard care. At 12 weeks, 7 of 18 patients (39%) in the TWO2 arm achieved complete healing versus 0 of 18 patients (0%) in the sham arm (p = 0.0076). The authors propose a multimodal therapeutic rationale: TWO2 delivers up to 10 litres of oxygen per minute under cyclical pressure directly to the wound surface, establishing a steep diffusion gradient that drives oxygen into hypoxic tissue even in areas of poor perfusion. This is combined with non-contact compression and humidification. A notable implementation advantage is that the device can be self-administered by patients at home, avoiding the cost and logistical burden of daily specialist clinic visits — particularly relevant for patients with mobility limitations or peripheral arterial disease. The authors position TWO2 as an adjunctive therapy for DFUs that fail other advanced treatments, rather than a first-line intervention.
Key Highlights:
- Primary outcome: 39% complete healing at 12 weeks with TWO2 vs. 0% with sham in moderately ischaemic DFUs (n=18 per arm; p=0.0076) — a statistically significant and clinically meaningful difference in a difficult-to-treat ischaemic population
- Patient eligibility: UT grade 1–2 DFUs (1–20 cm²), present 4 weeks to 1 year, failing ≥4 weeks of standard care; moderate ischaemia defined by IWGDF criteria (ABI ≥0.7, TBI <0.75, TcPO₂ <60, or equivalent Doppler/perfusion criteria)
- Multimodal mechanism: TWO2 combines cyclical pressurised oxygen (up to 10 L/min directly to wound surface), non-contact compression, and humidification — addressing ischaemia-driven hypoxia at the wound bed level through a steep diffusion gradient
- Home administration advantage: TWO2 can be self-applied by patients, eliminating daily specialist clinic visits — relevant for patients with PAD, mobility limitations, or in under-resourced settings where daily hyperbaric oxygen visits are impractical
- Ischaemia context: impaired microvascular circulation in DFUs disrupts oxygen-dependent cellular healing processes including fibroblast proliferation, epithelialisation, and collagen synthesis; restoring localised tissue oxygenation addresses the root physiological barrier
- Study design note: this is a post hoc subgroup analysis from a larger RCT (Frykberg et al., 2020 multinational trial); the relatively small n=18 per subgroup warrants interpretation with appropriate caution, and prospective confirmatory studies in ischaemic DFUs are needed
Keywords: topical oxygen therapy DFU, ischaemic diabetic foot ulcer treatment, TWO2 wound healing, cyclical oxygen compression wound, IWGDF peripheral arterial disease DFU, home wound therapy device
DiabetesontheNet Editorial / Contributing Authors