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: Interim Analysis

SLR - April 2022 - Aleksey Kozlov

Reference: Armstrong DG, Orgill DP, Galliano R, Glat PM, Didomenico AR, Snyder R, Li W, Carter M, Zelen C. 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: Interim Analysis. Int Wound J Jan; 19(1): 64-75

Level of Evidence: I

Scientific Literature Review

Reviewed By: Aleksey Kozlov, DPM
Residency Program: Highlands/Presbyterian St. Luke's Medical Center – Denver, CO

Podiatric Relevance: Podiatry plays an essential role in the multi-disciplinary approach to caring for patients with diabetes and subsequent lower extremity wounds. The mortality and morbidity associated with diabetic ulcers and the related amputation rates continue to be a tremendous burden and healthcare efforts remain focused on preventative care. This study aims to evaluate wound healing outcomes following the use of a novel autologous heterogeneous skin construct as adjunctive therapy to standard of care in Wagner stage 1 diabetic foot ulcers.

Methods: This study took patients with Wagner stage 1 diabetic foot ulcers and prospectively randomized them into two groups with one receiving adjunctive autologous tissue grafting as opposed to standard of care alone. Patients in the study groups underwent a 1 × 2 centimeters full-thickness harvest of healthy skin from the calf or thigh which was then specially treated for enhanced cellular induction at an outside facility and subsequently applied to the wound. The primary endpoint was the percentage of index ulcers healed at 12 weeks which the authors defined as 100% wound epithelialization without drainage. Other measured metrics included wound size reduction, changes in quality-of-life, pain reduction, changes in Semmes Weinstein monofilament test, and incidence of adverse events.

Results: The primary outcomes showed significantly higher wound closure rate of 72 percent in the treatment group versus 32 percent in the control group at 12 weeks. The treatment arm also achieved significantly greater percent area reduction compared to the control at 4, 6, 8, and 12 week timepoints. There was a total of 86 adverse events across the entire study population with 44 percent occurring in the treatment group and 56 percent in the control group. No major differences were noted regarding serious complications and no serious adverse events were related to the tissue treatment. Of the 25 patients in the treatment group, two required a second tissue application due to lack of integration. All tissue harvest sites were primarily closed and were fully healed at the final follow up. The treatment group reported greater increases in subjective quality-of-life improvements as well as a greater mean pain reduction compared to the control.

Conclusions: Lower extremity diabetic ulcerations continue to present a myriad of challenges to physicians tasked with their management. Research into tissue processing for enhanced inductive biocapacity is a growing field with ample capacity to improve wound regeneration rates. This article presents compelling early evidence for the utilization of these technologies in the treatment of lower extremity diabetic ulcerations. Despite having a small population, this interim study demonstrates promising results and sets the stage for more robust future investigations.