TOT in the Treatment of DFUs: Randomised controlled clinical trial (RCT)

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

Journal of Wound Care, May 2021

Author: Thomas E Serena, Neal M Bullock, Windy Cole, John Lantis, Lam Li, Sarah Moore, Keyur Patel, Matthew Sabo, Naz Wahab, Patricia Price

Keywords: chronic wound, clinical trial, diabetes, diabetic foot ulcer, DFU, dressing, hard-to-heal wound, infection, RCT, topical oxygen therapy, total contact casting, ulcer, wound

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).

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.

Key points:

  • 145 patients across 12 sites in the USA with a 24 week run-in period.
  • More than 50% of patients were age 65 or older.
  • Study compared SOC against SOC combined with NATROX® O₂.
  • 52% healed.
  • 71% greater healing rates with NATROX® O₂ compared to control.
  • 73% greater reduction in wound size using NATROX® O₂.
  • NATROX® O₂ received a p-value for both healing and wound size reduction, equating to 99.5% confidence that NATROX® O₂ made the difference.
  • Results offer hope to patients suffering from chronic wounds.


Serena TE, Bullock NM, Cole W et al, 2021. Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled trial. J Wound Care 2021; 30: Suppl.5 S7-14.

Video summary:

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