A multicentre, randomised controlled clinical trial evaluating the effects of a novel autologous, heterogeneous skin construct in the treatment of Wagner one diabetic foot ulcers: Interim analysis

Abstract

We desired to carefully evaluate a novel autologous heterogeneous skin construct in a prospective randomised clinical trial comparing this to a standard‐of‐care treatment in diabetic foot ulcers (DFUs). This study reports the interim analysis after the first half of the subjects have been analysed. Fifty patients (25 per group) with Wagner 1 ulcers were enrolled at 13 wound centres in the United States. Twenty‐three subjects underwent the autologous heterogeneous skin construct harvest and application procedure once; two subjects required two applications due to loss of the first application. The primary endpoint was the proportion of wounds closed at 12 weeks. There were significantly more wounds closed in the treatment group (18/25; 72%) vs controls (8/25; 32%) at 12 weeks. The treatment group achieved significantly greater percent area reduction compared to the control group at every prespecified timepoint of 4, 6, 8, and 12 weeks. Thirty‐eight adverse events occurred in 11 subjects (44%) in the treatment group vs 48 in 14 controls (56%), 6 of which required study removal. In the treatment group, there were no serious adverse events related to the index ulcer. Two adverse events (index ulcer cellulitis and bleeding) were possibly related to the autologous heterogeneous skin construct. Data from this planned interim analysis support that application of autologous heterogeneous skin construct may be potentially effective therapy for DFUs and provide supportive data to complete the planned study.

A multicenter, randomized controlled clinical trial evaluating the effects of a novel autologous heterogeneous skin construct in the treatment of Wagner one diabetic foot ulcers: Final analysis

“…This final RCT analysis confirmed the initial efficacy of AHSC found in the interim analysis of the first 50 enrolled subjects. 18 Healing rates at 12 weeks showed significantly more wounds closed in the AHSC group (70%-72%) than in the SOC only control group (32%-34%) (p < 0.005). For the secondary endpoint, the PARs were similar for both groups in the interim and final analyses at 4 and 12 weeks.…”

“…6,7 Among the 35 healed wounds, 33 (94.3%) healed within 12 weeks after only 1 application of AHSC, demonstrating that a single application of AHSC can populate the wound bed with sufficient regenerative cells possessing properties that are naturally found in healthy skin to promote wound closure and healing. 16,18,20,21 The potential cost-effectiveness of AHSC as a single application modality deserves further investigation. The AE rate was lower for the AHSC group than the control group (1.32 vs. 1.64), but in terms of severity and life-threatening events, they occurred similarly in both groups (Tables 8 and 9).…”

“…To achieve 89% power to detect a difference of 0.3 between the group proportions, a sample size of 102 (51 per group) was needed, which was confirmed by interim analysis of the first 50 enrolled subjects. 18 We assumed the proportion in the AHSC group to be 0.3 under the null hypothesis and 0.6 under the alternative hypothesis, and 0.3 was the proportion in the control group. The 2-sided Z test with pooled variance was the test statistic used.…”

“…Multiple studies support the safety and efficacy of a novel autologous heterogeneous skin construct (AHSC) as adjunctive therapy used on complex and chronic wounds. [8][9][10][11][12][13][14][15][16][17][18] The AHSC is manufactured from a small autologous harvest of the patient's full-thickness, healthy skin, containing the skin's natural endogenous regenerative cellular populations that facilitate healing. [13][14][15][16][17]19 Within just a few days of harvest, the AHSC is processed by an external facility, returned to the provider and applied to wound in the outpatient setting.…”

A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

“…Approximately 15–30% of diabetic individuals attain DFUs, leading to substantial wound management throughout their life. 37,38 The incidence of diabetes accounts for 8 out of 10 nontraumatic-type amputations. The percentage mortality ranges from 15–42% in 2 years, 34–64% in 4 years and 40–80% in 6 years.…”