An Observational Clinical Trial Examining the Effect of Topical Oxygen Therapy (Natrox^™) on the Rates of Healing of Chronic DiAbetic Foot Ulcers (OTONAL Trial)

Abstract

Natrox™ topical oxygen therapy (TOT) ( Inotec AMD Ltd, Cambridgeshire, UK) employs a small battery-powered “oxygen generator” to concentrate atmospheric oxygen and feeds pure, moist, oxygen through a fine, soft tube to a dressing-like “oxygen distribution system”, which is placed over the wound and is held in place by a conventional dressing. The aim was to determine the effectiveness of Natrox™ for non-healing diabetic foot ulcers (DFU) over a 3-month period.Longitudinal, single-arm, open prospective registry study using 12 weeks of TOT using a 4 week run-in period. 20 patients recruited to OTONAL had chronic DFU greater than 3 months duration or minor amputation sites with less than 50% healing in 4 weeks.There were 13 (65%) males and the mean age was 65.7 (±11.6) years. The mean glycated haemoglobin (HbA1c) was 6.9 (±1.3) mmol mol−1 and mean wound duration before TOT was 114 (±79.1) days. 18/20 (90.0%) patients had concomitant lower limb revascularization angioplasty for chronic limb threatening ischaemia. The mean size of the foot ulcer at baseline was 11.3 ± 14.8 cm2 and mean transcutaneous oxygen measurement value was 34.1 (±19.6) mm Hg. Wound closure of >75% was observed in 14/20 (70.0%) patients. There was a 91.3% (±14.9%) wound area reduction by 3 months (P = .001) and mean time for 100% closure was 77.6 ± 32.5 days. Mean pain scores reduced from 2.4 (±1.8) at baseline to .5 (±1.0) at 3 months (P = .008). All patients were very satisfied using the ambulatory device. Use of TOT in chronic diabetic foot wounds stimulates a healing state, underpinning the concept that oxygen plays a central role in wound healing. Our results are more compelling if you consider they started with relatively large-sized DFUs and majority of patients were frail with underlying peripheral artery disease. (NCT03863054)

KADAM topical warm oxygen therapy device for diabetic foot ulcer-a novel approach

“…Reduction in wound area by 3 months was 91.3% with mean time for complete closure being 77.6 ± 32.5 days [15]. This difference in mean time for 100% closure was much higher when compared to the present study [15]. The present study delivered fewer sessions and obtained similar results in wound closure.…”

“…The OTONAL trail by Tang T.Y et al, 2021 observed wound closure of more than 75% in 70% of its study participants. Reduction in wound area by 3 months was 91.3% with mean time for complete closure being 77.6 ± 32.5 days [15]. This difference in mean time for 100% closure was much higher when compared to the present study [15].…”

“…The DFUs of different grades 1, 2 and 3 in the study showed complete healing with full wound closure. However, in previous studies that used topical continuous oxygen therapy alone without warmth, marginal reduction was observed in the diabetic foot ulcer size [11][12][13][14][15][16][24][25][26][27]. This suggests that addition of warmth to continuous delivery of topical oxygen, enhances the healing capacity of wound through an alteration in the wound healing mechanism.…”

“…The significance of topical oxygen and its various routes of application in the healing of chronic DFUs has previously been explored [9,[13][14][15][16]. The use of topical warm oxygen therapy has still not been investigated thoroughly.…”

Oxygen Therapy to Enhance Wound Healing After Revascularization

“…Tang TY et al conducted an observational clinical trial on chronic DFU with an oxygen generator device (Natrox TM ) reported >75% of wound closure with pain reduction. 54 The mean TcpO 2 of the population in this trial is 34.1 ± 19.6 mm Hg with 18 of 20 patients having a history of previous endovascular revascularization procedure treatment. There is no control group to compare in the result.…”