LeucoPatch Promising in Hard-to-Heal Diabetic Foot Ulcers

Becky McCall

September 28, 2018

Patches consisting of autologous leucocytes, platelets, and fibrin (LeucoPatch, Reapplix) are associated with a significant increase in the proportion of wounds confirmed healed when added to good standard of care, show results of a large randomized trial of hard-to-heal diabetic foot ulcers.

The findings show "a significantly higher incidence of healing within 20 weeks (unadjusted odds ratio, 1.58) in patients receiving LeucoPatch applications, a bedside treatment...compared with good quality standard care," write the researchers led by Frances Game, MD, consultant diabetologist at Derby Teaching Hospitals NHS Foundation Trust, UK. 

"This trial shows a clinically and statistically significant benefit associated with the weekly application of autologous immune cell, fibrin, and platelet patches (LeucoPatch)...The treatment was without apparent adverse events, specifically without evidence of new onset anemia," say Game and colleagues in their in their article published online September 19 in The Lancet Diabetes and Endocrinology.

In an accompanying commentary, Michael Edmonds, from the Diabetic Foot Clinic, King's College Hospital, London, UK, says: "Regardless of the management of the vasculature, there was a significant benefit from the intervention in the hard-to-heal ulcers,” and “the low number of dropouts suggests good patient acceptability."

And although he notes that "the procedure can be done at the bedside by centrifugation of an 18-mL blood sample over 20 minutes without the addition of reagents, which was necessary in previous platelet-derived applications," he still wonders, "How easy would it be to deliver LeucoPatch in the context of a busy diabetic foot clinic, and is it cost effective?"

Noting a cost-effectiveness study is ongoing, he says these data will be welcome. 

First-of-Its-Kind Trial

According to the researchers, the trial is the first of its kind to study the multilayer patches that are generated at the bedside without the addition of reagents. The patch exerts its effect by releasing cytokines and growth factors involved in tissue repair.

Diabetic foot ulcers can take a long time to improve, and even after healing the wounds have a high incidence of new ulceration of approximately 40% at 12 months.

There are a lack of proven treatments for these hard-to-heal wounds, but the recent development of multilayered patches is a possible new option, write the researchers.

The trial aimed to determine whether the application of LeucoPatch, when used in addition to standard care, is superior to standard care alone in healing hard-to-heal diabetic foot ulcers not infected at time of randomization.

A total of 595 people with diabetes and foot ulcers from specialist diabetic foot clinics in the UK, Sweden, and Denmark were recruited. After a 4-week run-in period, patients were included if they experienced a less than 50% reduction in ulcer area, which eliminated 326 patients, leaving only patients with hard-to-heal ulcers.

Of the remaining 269 patients, 137 were randomized to standard care and 132 to the additional application of LeucoPatch. The mean age of participants was 61.9 years, 82% were men, 83% had type 2 diabetes, and median HbA1c was 8.2%. Most ulcers were greater than 100 mm2.

The primary outcome was the proportion of ulcers that healed within 20 weeks assessed in the intention-to-treat population, with "healed" defined as complete epithelialization (confirmed by a masked observer and backed up by digital imaging) that remained healed for 4 weeks.

Improved and Faster Healing With LeucoPatch, but Not Fewer Infections

According to the intention-to-treat analysis, in the LeucoPatch group, 45 (34%) of 132 ulcers healed within 20 weeks versus 29 (22%) of 134 ulcers in the standard care group (odds ratio, 1.58; P = .0235). Also, median time to healing was shorter in the LeucoPatch than the standard care group at 72 days versus 84 days (P = .0343).

There was no difference between the intervention (patch) and standard of care groups in terms of adverse events, including the number of major or minor amputations. The most common serious adverse event was diabetic foot infection, with 24 events in the LeucoPatch group (24% of all serious adverse events) and 20 events in the standard care group (27% of all serious adverse events). There were no device-related adverse events.

"In particular, there was no increased incidence of anemia in the intervention group — even in those with reduced glomerular filtration rate — despite the need for weekly venesection," say Game and colleagues.

Likewise, clinical infection and antibiotic use did not differ between the groups, even though a difference might have been expected because of the leucocytes contained within the application, add the authors.

In his commentary, Edmonds points out that given LeucoPatch delivers autologous neutrophils, macrophages, and platelets to the ulcer, it "might have been expected to prevent diabetic foot infection. However, the incidence of episodes of clinical infection did not differ between the two groups."

"Despite patients being under weekly supervision during the trial, new episodes of infection still developed," he notes, adding that "the prevention of infection remains a challenge."

Edmonds has declared receiving personal fees and honoraria from Laboratoires Urgo Medical, Edixomed, Integra Lifesciences Services, Knox Technologies, and Bayer. Co-authors Lise Tarnow and Magnus Löndahl have received research support from Reapplix. The other authors have reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online September 19, 2018. Abstract, Commentary

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