A randomised, controlled multicentre clinical trial was conducted at 14 wound care centres in the United States to confirm the efficacy of dehydrated human amnion/chorion membrane allograft (dHACM) for the treatment of chronic lower extremity ulcers in persons with diabetes. Patients with a lower extremity ulcer of at least 4 weeks duration were entered into a 2-week study run-in phase and treated with alginate wound dressings and appropriate offloading. Those with less than or equal to 25% wound closure after run-in were randomly assigned to receive weekly dHACM application in addition to offloading or standard of care with alginate wound dressings, for 12 weeks. A total of 110 patients were included in the intent-to-treat (ITT) analysis, with n = 54 in the dHACM group and n = 56 in the no-dHACM group. Of the participants, 98 completed the study per protocol, with 47 receiving dHACM and 51 not receiving dHACM. The primary study outcome was percentage of study ulcers completely healed in 12 weeks, with both ITT and per-protocol participants receiving weekly dHACM significantly more likely to completely heal than those not receiving dHACM (ITT-70% versus 50%, P = 0.0338, per-protocol-81% versus 55%, P = 0.0093). A Kaplan-Meier analysis was performed to compare the time-to-healing performance with/without dHACM, showing a significantly improved time to healing with the use of allograft, log-rank P < 0.0187. Cox regression analysis showed that dHACM-treated subjects were more than twice as likely to heal completely within 12 weeks than no-dHACM subjects (HR: 2.15, 95% confidence interval 1.30-3.57, P = 0.003). At the final follow up at 16 weeks, 95% of dHACM-healed ulcers and 86% of healed ulcers in the no-dHACM group remained closed. These results confirm that dHACM is an efficacious treatment for lower extremity ulcers in a heterogeneous patient population.

AimsAmong people with diabetes, 10–25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and β-hydroxy-β-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes.MethodsAlong with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and β-hydroxy-β-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle–brachial index, and supplementation on healing was investigated.ResultsOverall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle–brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and β-hydroxy-β-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04–2.79) and 1.66 (95% CI 1.15–2.38) times more likely to heal.ConclusionsWhile no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and β-hydroxy-β-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and β-hydroxy-β-methylbutyrate in these high-risk subgroups might prove clinically valuable.

At the end of an anatomic peninsula, the foot in diabetes is prone to acute and chronic complications involving neuropathy, vasculopathy, and infection. Effective management requires an interdisciplinary effort focusing on this triad. In this article, we describe the key factors leading to foot complications and the critical skill sets required to assemble a team to care for them. Although specific attention is given to a conjoined model involving podiatry and vascular surgery, the "toe and flow" model, we further outline three separate models of care--basic, intermediate, and center of excellence--that can be implemented in the developed and developing world.

The aim of this study was to determine the safety and effectiveness of dehydrated human umbilical cord allograft (EpiCord) compared with alginate wound dressings for the treatment of chronic, non‐healing diabetic foot ulcers (DFU). A multicentre, randomised, controlled, clinical trial was conducted at 11 centres in the United States. Individuals with a confirmed diagnosis of Type 1 or Type 2 diabetes presenting with a 1 to 15 cm2 ulcer located below the ankle that had been persisting for at least 30 days were eligible for the 14‐day study run‐in phase. After 14 days of weekly debridement, moist wound therapy, and off‐loading, those with ≤30% wound area reduction post‐debridement (n = 155) were randomised in a 2:1 ratio to receive a weekly application of EpiCord (n = 101) or standardised therapy with alginate wound dressing, non‐adherent silicone dressing, absorbent non‐adhesive hydropolymer secondary dressing, and gauze bandage roll (n = 54). All wounds continued to have appropriate off‐loading during the treatment phase of the study. Study visits were conducted for 12 weeks. At each weekly visit, the DFU was cleaned and debrided as necessary, with the wound photographed pre‐ and post‐debridement and measured before the application of treatment group‐specific dressings. A follow‐up visit was performed at week 16. The primary study end point was the percentage of complete closure of the study ulcer within 12 weeks, as assessed by Silhouette camera. Data for randomised subjects meeting study inclusion criteria were included in an intent‐to‐treat (ITT) analysis. Additional analysis was conducted on a group of subjects (n = 134) who completed the study per protocol (PP) (EpiCord, n = 86, alginate, n = 48) and for those subjects receiving adequate debridement (EpiCord, n = 67, alginate, n = 40). ITT analysis showed that DFUs treated with EpiCord were more likely to heal within 12 weeks than those receiving alginate dressings, 71 of 101 (70%) vs 26 of 54 (48%) for EpiCord and alginate dressings, respectively, P = 0.0089. Healing rates at 12 weeks for subjects treated PP were 70 of 86 (81%) for EpiCord‐treated and 26 of 48 (54%) for alginate‐treated DFUs, P = 0.0013. For those DFUs that received adequate debridement (n = 107, ITT population), 64 of 67 (96%) of the EpiCord‐treated ulcers healed completely within 12 weeks, compared with 26 of 40 (65%) of adequately debrided alginate‐treated ulcers, P < 0.0001. Seventy‐five subjects experienced at least one adverse event, with a total of 160 adverse events recorded. There were no adverse events related to either EpiCord or alginate dressings. These results demonstrate the safety and efficacy of EpiCord as a treatment for non‐healing DFUs.

Aim: The purpose of this clinical trial was to evaluate the safety and efficacy of a fetal bovine acellular dermal matrix (FBADM) plus standard of care (SOC) for treating hard-to-heal diabetic foot ulcers (DFUs). Method: A prospective, multi-centre, randomised controlled trial was carried out. The study included a 2-week run-in period, a 12-week treatment phase and a 4-week follow-up phase. The primary endpoint was complete wound closure at 12 weeks. Results: Twenty-one US sites enrolled and randomised 226 patients with hard-to-heal DFUs. The study was terminated early due to the COVID-19 pandemic, which led to a modified intent-to-treat (mITT) population of 207 patients, with 103 in the FBADM group and 104 in the SOC group. Of these participants, 161 completed the study per protocol (mPP population), with 79 receiving FBADM, and 82 without. At the first analysis point, patients treated with FBADM were found to be significantly more likely to achieve complete wound closure compared with SOC alone (mITT: 45.6% versus 27.9% p=0.008; mPP: 59.5% versus 35.6% p=0.002). The difference in outcome yielded an odds ratio of 2.2 (95% confidence interval (CI): 1.2, 3.9; p=0.008). Median time to closure within 12 weeks was 43 days for the FBADM group compared to 57 days for the SOC group (p=0.36). The median number of applications of FBADM to achieve closure was one. Adverse events were similar between groups and no product-related serious adverse events occurred. Conclusions: These results indicate that in many cases a single application of FBADM in conjunction with SOC offers a safe, faster and more effective treatment of DFUs than SOC alone.