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 for medtech innovation briefings. 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 8 studies summarised in this briefing, including a total of 530 people.

The included studies are 1 meta-analysis, 2 randomised controlled trials and 5 non-comparative observational studies (case series). The meta-analysis includes 3 retrospective cohort control studies across various wound types (Hunt et al. 2018, Hunt and Elg 2017 and Hunt and Elg 2016). Hunt et al. (2016) is an extension to the Haycocks et al. (2016) study. There are over 25 further published studies evaluating the technology across multiple indications.

The clinical evidence and its strengths and limitations is summarised in the overall assessment of the evidence.

Overall assessment of the evidence

The evidence base for the technology is of low to good methodological quality and most studies have small sample sizes. Seven studies were based in the UK and are generalisable to clinical practice in the NHS. In general, the evidence suggests that Granulox may lead to a reduction in wound size and pain across various wound types. One randomised controlled trial suggests that Granulox has no effect on wound healing outcomes in foot ulcers. However, this study was small and insufficiently powered. Further evidence would benefit from sufficiently powered sample sizes and randomised controlled trials focusing on complete wound healing and long-term follow up.

Elg and Hunt (2018)

Intervention and comparator

Standard care plus Granulox compared with standard care.

Key outcomes

The meta-analysis included 340 people, of whom 170 had Granulox therapy. Five wound subtypes were identified from the 3 studies with 10 or more people in both groups: trauma (n=110), diabetic foot ulcer (n=60), venous leg ulcer (n=33), burn (n=30), post-surgery (n=24). Other wound types with less than 10 people in each group were included in the analysis (n=83). The Granulox group showed a significantly higher weekly chance of healing in the following wound types (beta, 95% range, sample and p value); trauma 1.55 (1.23 to 1.96, n=110, p<0.001), diabetic foot ulcer 2.39 (1.52 to 3.75, n=60, p<0.01), burns 1.82 (1.11 to 2.99, n=30, p=0.02) and post-surgical wounds 2.75 (1.53 to 4.96, n=24, p=0.001). Kaplan–Meier analysis for venous leg ulcers also suggested a statistically significant benefit in the Granulox group, p<0.001 (n=33). Across the 5 wound types, the overall beta (95% range, sample and p value) was 1.86 (1.58 to 2.19, n=257, p<0.001). Average reported pain scores were significantly lower within 2 weeks for the Granulox group compared with the control group (all p<0.01, t‑test) with a 49% to 78% greater reduction in pain scores. The difference in wound size reduction between the groups after 4 weeks showed an average 49% to 102% greater reduction in wound size in the Granulox group (all p=0.02 or lower).

Strengths and limitations

This study suggests that Granulox may improve wound healing outcomes across various wound types. The study evaluated the Granulox groups by comparing them with retrospective standard care cohorts from the same clinics and time period. The main limitations of this study are the lack of prospective randomisation and blinding. Without this, wound healing cannot be definitively attributed to Granulox. This study was funded by SastoMed GmbH, a company owned by Mölnlycke Health Care.

Arenbergerova et al. (2013)

Intervention and comparator

Granulox compared with 0.9% saline solution.

Key outcomes

There were 65 out of 72 people who completed the study. After 13 weeks, 33 people in the Granulox group had a reduction in wound surface area and 1 person had an increased wound surface area. The average reduction in the wound surface area for the Granulox group was 53.4% (p<0001 compared with the beginning of the study). In the control group, 14 out of 31 people had a reduction in wound surface area and 17 people had an increase in wound surface area. After 13 weeks, the average wound surface area of the control group had increased from 17.5 cm2 to 20.2 cm2.

Strengths and limitations

This study is the only randomised trial for Granulox in people with venous leg ulcers and suggests that the application of Granulox may improve wound healing. The study was completed in Germany and so may not be generalisable to the NHS.

Jonker et al. (2021)

Intervention and comparator

Standard care plus twice weekly Granulox therapy compared with standard care (once weekly podiatric medical clinic visits).

Key outcomes

There were 29 out of 38 people who completed the study. One person withdrew and 2 were lost to follow up in the control group. Five people withdrew and 1 was lost to follow up in the Granulox group. After 6 weeks, 4 out of 16 foot ulcers had healed in the control group, and 3 out of 16 had healed in the Granulox group (p>0.99, Fisher exact test). After 12 weeks, 8 out of 14 foot ulcers had healed in the control group, and 3 out of 13 had healed in the Granulox group (p=0.12, Fisher exact test). The median healing rate for the control group was 100% compared with 48% in the Granulox group. One serious adverse event happened in the Granulox group compared with 2 in the control group; none were related to the treatment.

Strengths and limitations

This study is the only randomised controlled trial for Granulox in people with foot ulcers but it has several limitations. The study was not blinded, there was no sham treatment for the control group and randomisation was not stratified by wound chronicity. The study was not adequately powered to show statistical significance between the groups.

Bateman (2015a)

Intervention and comparator

Standard care plus Granulox, no comparator.

Key outcomes

After 4 weeks of treatment and a 5‑week follow-up period, all 25 wounds had reduced in size, and 76% (n=19) of wounds had completely healed. Slough levels had reduced in 68% (n=17) of people after 2 weeks, and 100% of people after 3 weeks.

Strengths and limitations

The main limitation of this study is the non-comparative design. Without a control, wound healing cannot be attributed to Granulox. The study also has a small sample size and short follow-up period.

Bateman (2015b)

Intervention and comparator

Standard care plus Granulox, no comparator.

Key outcomes

After 4 weeks, the average reduction in wound size was 62.3%. Five out of 20 diabetic foot ulcers had healed. The remaining 15 out of 20 diabetic foot ulcers showed a reduction in wound size.

Strengths and limitations

The main limitation of this study is the non-comparative design. Without a control, wound healing cannot be attributed to Granulox.

Tickle (2015)

Intervention and comparator

Standard care plus Granulox, no comparator.

Key outcomes

After 4 weeks, 17 out of 18 wounds had reduced in size. The average wound size was 3.39 cm2 compared to 11.23 cm2 at the beginning of the study. All 18 people reported an improvement in their pain severity score during the study, with an average score of 2.5 compared with 6.2 (on a scale of 0 to 10) at the beginning of the study.

Strengths and limitations

This study has restricted value because of the small sample size and lack of control. Granulox application varied between people because of the variation in wound size and exudate levels.

Haycocks et al. (2016)

Intervention and comparator

Standard care plus Granulox, no comparator.

Key outcomes

There were 16 out of 17 people who completed the study. One person with 2 wounds was withdrawn because of infection. After 4 weeks, 14 out of 18 wounds showed a positive reduction in wound size. There was an average reduction in wound size of 53.8% (standard deviation 26.6; range 11.9% to 100%) over 4 weeks. Two wounds showed no reduction in size during the study. The remaining 4 wounds showed an increase in size or did not change.

Strengths and limitations

The main limitation of this study is the non-comparative design. Without a control, wound healing cannot be attributed to Granulox. Local guidelines on standard care between the 6 participating centres may have varied. The method of wound measurement was subjective and may have resulted in overestimation of wound area.

Hunt et al. (2016)

Intervention and comparator

Standard care plus Granulox, no comparator.

Key outcomes

All 13 people (with 15 wounds) completed the study. After 12 weeks, 3 wounds had healed, and 8 wounds had shown a reduction in wound size. Three wounds had increased in size.

Strengths and limitations

The main limitation of this study is the non-comparative design and small sample size. Without a control, wound healing cannot be attributed to Granulox. Local guidelines on standard care between the participating centres may have varied.

Sustainability

The company claims that the technology could reduce the number of dressing changes meaning that community vehicle journeys will be reduced. The company also claims that the technology could lower infection rates, reducing the need for antibiotic medicine. There is no published evidence to support these claims.

Recent and ongoing studies

A multicentre European study to evaluate Granulox used in the treatment pathway of predominantly chronic venous leg ulcers (VLUs). ClinicalTrials.gov identifier: NCT04181320. Status: recruiting. Indication: venous leg ulcer. Devices: venous leg ulcer standard of care with Granulox. Estimated study completion date: 31 December 2022. Countries: France, Germany, Hungary, UK, Poland, Croatia and Czech Republic.