Advice

Clinical and technical evidence

Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.

Published evidence

There are 3 studies summarised in this briefing. They included 172 patients, 162 of whom received NATROX therapy.

The evidence indicates oxygen therapy could be effective for non-healing wounds. But more clinical evidence on larger cohorts of patients is needed from controlled trials and larger real-world populations to establish its effectiveness. Studies in 1 wound type would establish which wounds benefit most from the technology.

Overall assessment of the evidence

There is not much good-quality evidence: 1 small, high-quality randomised controlled trial and 2 larger observational studies. There are several abstracts and other publications describing individual cases, but these do not add to the substantive studies below.

The evidence shows an effect from the NATROX device, but the relatively small numbers of patients and heterogeneous populations means definitive conclusions are difficult. Only 1 study includes NHS data, but non-NHS pathways and the epidemiology of non-healing wounds and diabetic foot ulcers appear similar across all sources.

Yu et al. (2016)

Study size, design and location

Randomised controlled trial including 20 patients with diabetic foot ulcers, Canada.

Intervention and comparator(s)

NATROX compared with 'standard best practice'; NATROX used once a week for 8 weeks.

Key outcomes

Ulcer surface area over time was analysed using standardised digital imaging software. Wound size was significantly reduced compared with baseline in the NATROX group (F [2.238, 20.146] 58.885, p<0.001) and not significant in the control group (F [1.186, 10.674] 51.447, p<0.262). Ulcers were present without healing for a mean duration of 76 weeks before the study. All grade 1 ulcers in both groups healed (complete wound closure); all grade 2 ulcers in the NATROX group healed compared with none in the control group; 50% of grade 3 ulcers healed with NATROX compared with none in the control group.

Strengths and limitations

This was a high-quality study with well-defined interventions and patient groups. Ulcers were graded with the widely used University of Texas diabetic foot ulcer classification. A limitation was its small size, with only 10 patients receiving the intervention. Generalisability to the UK is not clear as the study was in Canada.

Kaufman et al. (2018)

Study size, design and location

Real-world observational study on 100 consecutive cases, Israel.

Intervention and comparator(s)

Continuous oxygen delivery using NATROX for an average duration of 40.3 days; no comparator.

Key outcomes

The cases included 48 venous leg ulcers, 27 arterial ulcers, 13 diabetic foot ulcers and 12 others (trauma, burns, post-op and pressure ulcers). Adherence with the treatment was 88% and there was a mean reduction in wound area of 7% per week. For patients treated for more than 25 days, 31 of 65 wounds healed completely. There were no statistically significant differences between the groups, but non-healing ulcers tended to be larger and have a longer duration.

Strengths and limitations

This study is of low methodological quality but includes important real-world data from consecutive cases, although it is a relatively small real-world study. The mixture of types and duration of wounds and patients make clear conclusions difficult. Generalisability to the UK is not clear as the study was undertaken in Israel.

Hayes (2017)

Study size, design and location

Multicentre observational study on 52 diabetic foot ulcer cases, UK.

Intervention and comparator(s)

Continuous oxygen delivery using NATROX for an average duration of 24 weeks; no comparator.

Key outcomes

The median duration of diabetic foot ulcer before the trial was 12 months. The median ulcer size decreased from 1.8 cm2 to 0.15 cm2 over 24 weeks. At 8 weeks the median ulcer size reduction was 48%. At 12 weeks 42% of ulcers had healed completely and 14% showed more than 80% re-epithelialisation.

Strengths and limitations

This study included 18 UK NHS tertiary care sites. Standardised digital images were used to report wound size. The study is reported as an abstract and is limited in methodological detail; patient demographic data are not reported. Only descriptive statistics were reported, and the lack of a comparator limits the usefulness of these data. The abstract does not reference NATROX specifically, however, these are preliminary data from a randomised controlled trial in the UK investigating NATROX in diabetic foot ulcers.

Sustainability

The company states the NATROX Oxygen Generator is reusable and can be recycled at an appropriate facility, or through the company. The NATROX device complies with all relevant medical device disposal directives.

Recent and ongoing studies