Dressing Hastens Neuroischemic Diabetic Foot Ulcer Healing

Miriam E Tucker

January 03, 2018

Sucrose octasulfate dressing (UrgoStart Contact, Laboratoires Urgo Medical) shows promise as an option for treating neuroischemic diabetic foot ulcers, new research finds.

Results from a randomized, controlled, double-blinded, 20-week trial were published online December 20 in Lancet Diabetes & Endocrinology by Michael Edmonds, MD, of the King's College Hospital Diabetic Foot Clinic, London, United Kingdom, and colleagues.   

Currently there are no proven treatments for neuroischemic ulcers, defined as those arising in the presence of both peripheral neuropathy and peripheral arterial disease, with the latter condition significantly worsening prognosis.  

"Overall, neuroischemic ulcers constitute about 50% of total [diabetic foot] ulcers and should benefit from sucrose octasulfate," Dr Edmonds told Medscape Medical News.

The potassium salt of sucrose octasulfate acts at the tissue level to inhibit excess matrix metalloproteinases, which impede wound healing by the degradation of growth factors and destruction of the extracellular matrix. The ingredient also acts to restore growth factor function and tissue formation.

In the study, which compared sucrose octasulfate to placebo dressing in 240 patients with neuroischemic diabetic foot ulcers, wound healing was significantly improved among patients given the active dressing.

"A sucrose octasulfate dressing is effective and safe, and its use is easy to implement by all healthcare professionals. This dressing could form an important part of modern multidisciplinary management of neuroischemic diabetic foot ulcers," the authors write.

In an accompanying editorial, Frances L Game, MBBCh, of the department of diabetes and endocrinology, Derby Teaching Hospitals NHS Foundation Trust, United Kingdom, writes: "Sucrose octasulfate dressings seem to be a promising addition to our current treatment strategies for diabetic foot ulcers positioned away from the heel, which have not shown a significant reduction in area despite good offloading and other best practice treatments, and where patients also have peripheral arterial disease that is not being considered for vascular intervention."

However, she also questioned the generalizability of the findings, given some of the study's exclusion criteria based on ulcer location and size, and the presence of infection.

Greater Wound Closure, and Faster

The study was conducted in 43 hospitals with specialty diabetes foot clinics in France, Spain, Italy, Germany, and the United Kingdom. Between March 2013 and March 2016, a total of 126 patients with noninfected neuroischemic diabetic foot ulcers greater than 1 cm² were randomized to sucrose octasulfate dressing and 114 to placebo dressing. Otherwise, all patients received the same standard of care — including an offloading device — throughout the 2-week screening period and 20-week trial.

Dressings were applied by nursing staff or the patient's relatives, with frequency of dressing changes individually determined based on wound condition. Median treatment duration was 115 days for the sucrose octasulfate dressing and 135 days for controls.

The primary outcome, wound closure at week 20, was achieved in 48% of the sucrose octasulfate treatment group vs 30% of controls, giving an adjusted odds ratio (OR) of 2.6 (P=.002).

The only other significant variable that predicted the primary outcome was duration of wound prior to treatment. Those whose wounds had been present for more than 6 months prior had a much lower rate of wound closure at week 20 compared with those whose wounds had been present for less than 6 months (OR, 0.27; P<.001).

"Better outcomes were reached in wounds with a duration of less than 6 months. Although we did not do an analysis of significance because of the small size of the subgroups, it seems reasonable to recommend treating wounds as soon as possible," Dr Edmonds and colleagues note.

The estimated time to wound closure was also significantly shorter with the active treatment vs placebo, at 120 vs 180 days (P=.029).

Greater reductions in absolute and relative wound surface area and faster wound re-epithelialization were also seen at week 20 in the sucrose octasulfate group compared with controls.

Downsides

Quality of life, assessed by the EuroQol-5D-5L questionnaire, was similar between groups at week 20 and remained poor overall. This was driven primarily by the two questionnaire domains of mobility and activity. (The other three domains are self-care, pain/discomfort, and anxiety/depression.)

Dr Edmonds told Medscape Medical News, "The overall reduction in quality of life in these patients may not be so much related to the ulcer, but more to the underlying diabetes, peripheral neuropathy, and arterial disease that would not have been affected by the dressing or healing of the ulcer."

Moreover, he noted, neuroischemic ulcers usually aren't painful because of the associated neuropathy unless they become infected, and infected ulcers weren't included in the study. Thus, the actual ulcer healing may not have significantly affected quality of life scores.

In both groups, the most frequent adverse events were infection of the target wound, which occurred in 28% with sucrose octasulfate vs 20% of controls. Minor amputations were reported in 1% with treatment vs 2% of controls. 

How Generalizable Are the Results?

Dr Edmonds emphasizes that the findings are relevant to patients with neuroischemic diabetic foot ulcers and not critically ischemic feet, for which urgent revascularization is required.

In her editorial, Dr Game writes, "a sucrose octasulfate dressing might not necessarily be suitable for all diabetic foot ulcers," as this study had excluded ulcers located on the heel, infected ulcers, and those less than 1 cm2 in size.

In the 2016 National Diabetes Foot Audit (NDFA) of England and Wales, those conditions were present in 20%, 43%, and 52% of all ulcers, she notes.

But Dr Edmonds points out that about a third of the NDFA ulcers are ischemic rather than neuroischemic. Moreover, other data such as those of the Eurodiale study (Diabetologia 2007;50:18-25) suggest that heel location may comprise just 11% and average wound size may also be smaller than reported by the NDFA. 

"We cannot be sure that the significant difference of outcomes reported in this trial can be extrapolated to patients with neuroischemic diabetic foot ulcers of less than 1 cm². However, the generalizability of the protocol is probably greater than the NDFA would suggest," he told Medscape Medical News.

Indeed, while urging that confirmation of the study's generalizability is needed, Dr Game commented, "The results are certainly more encouraging than findings for most interventions that have been reported to date. Additionally, although the results of a full health economic analysis are awaited, it is evident that the sucrose octasulfate dressing is easy to apply, and therefore, apart from the dressing itself, there should be no additional costs in a treated patient's clinical pathway."

UrgoStart Contact is on the market in some European countries and the United Kingdom, but not yet in the United States.

Laboratoires Urgo Medical plans to apply for US approval of UrgoStart Contact this year, using the current study as the basis for the application.

The study was funded by Laboratoires Urgo Medical. Dr Edmonds reports receiving personal fees from Edixomed, Knox technologies, and Crawford. Dr Game has reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online December 20, 2017. Abstract, Editorial

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