A comparative effectiveness research study of a native Type I collagen matrix plus polyhexamethylene biguanide antimicrobial and a cryopreserved cadaveric skin allograft for use in diabetic foot ulcers – a non-inferiority analysis

OBJECTIVE: Real-world effectiveness was evaluated in a large patient population at 246 US treatment facilities comparing a purified native cross-linked extracellular matrix plus polyhexamethylene biguanide antimicrobial barrier (PCMP)(a) and a cryopreserved cadaveric skin allograft (CCSA)(b) for use in diabetic foot ulcers (DFUs). METHODS: Electronic medical records collected(c) of 841 patients (917 DFUs) from 2014-2020 were analyzed. Exclusion criteria were lack of baseline wound measurements or follow-up visits. Evaluations were performed on 264 PCMP-treated patients (291 DFUs), and 577 CCSA-treated patients (626 DFUs). Cox analyses that included ulcer size, depth, and duration were used to compute frequency and probability of wound closure. A non-inferiority (NI) analysis was used to determine whether the lower limit of the confidence interval (CI) was greater than 0.8. RESULTS: Treatment cohorts were comparable for patient demographics, wound, and treatment characteristics. Baseline, mean areas (SD) were 5.8 (10.6) and 7.9 (15.7) cm2, mean depths were 3.9 (4.2) and 3.5 (3.5) mm, and median durations were 9.4 (16.4) and 7.1 !10.5) months for PCMP and CCSA, respectively. The median number of treatment applications was 2.0 in both groups, and the mean interval between treatment applications was 14.6 (18.5) vs 24.3 (24.5) days for PCMP and CCSA, respectively. The PCMP vs CCSA frequencies of wound closure were comparable at all study timepoints including week 4 (10 vs 8%), 8 (22 vs 19%), and 12 (34 vs 34%) respectively (p=0.44). PCMP demonstrated a comparable probability of wound healing vs CCSA treatment (Hazard Ratio=0.99; p=0.95. PCMP showed equivalence to CCSA [90% CI (0.85, 1.17)] when tested at a clinical margin of 20% (p=0.01). CONCLUSIONS: The NI design demonstrated statistically significant equivalence between PCMP and CCSA at the clinical margin tested. These findings may inform wound care treatment algorithms and have meaningful clinical and health care economic implications.