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 venous leg ulcers – a non-inferiority analysis

OBJECTIVES: Real-world effectiveness was evaluated in a large patient population at 212 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 venous leg ulcers (VLUs). 

METHODS: Electronic medical records(c) were the source of these retrospective data. Treatment records collected from 2011-2019 on 981 patients (1,111 VLUs) were analyzed. Key exclusion criteria included lack of baseline wound measurements or follow-up visits, and third degree burns. Evaluations were performed on 312 PCMP patients (364 VLUs), and 669 CCSA patients (747 VLUs). A Cox Proportional Hazards regression analysis (Cox) that adjusted for variables including ulcer area and duration was used to compute frequency, time to, and probability of wound closure. 

RESULTS: Baseline, mean areas were 20.1 and 25.5 cm2, mean depths were 2.1 and 2.0 mm, and median durations were 16.0 and 13.7 months, for PCMP and CCSA, respectively. The mean number of treatment applications was 2.6 in both groups, and the mean interval between treatment applications was 15.6 vs 32.4 days for PCMP and CCSA, respectively. The PCMP vs CCSA frequencies of wound closure were comparable at all study timepoints including week 8 (21 vs 17%), 12 (31 vs 28%), 18 (41 vs 40%), and 24 (48 vs 48%), respectively (p=0.99). PCMP demonstrated a comparable probability of wound healing vs CCSA treatment; Hazard Ratio=0.99 [90% CI (0.85, 1.15)]; p=0.99). In a Non-Inferiority (NI) analysis, PCMB demonstrated equivalence to CCSA when tested at a clinical margin of 20% (p=0.01).

CONCLUSIONS: The NI design allows a valid conclusion of equivalence between PCMP and CCSA at a level of significance < 0.05 at the clinical margin tested. These findings may inform wound care treatment practices and impact health care economics.