Comparative Efficacy of High Purity Type I Collagen-Based Skin Substitute and Dehydrated Human Amnion/Chorion Membrane in Diabetic Foot Ulcers: A Multicentre Randomized Controlled Trial.

backgroundDiabetic foot ulcers (DFUs) are a major healthcare challenge due to their chronic nature, high recurrence rate, and the substantial morbidity they impose. Effective treatment remains limited, which underscores the need for advanced wound care approaches. High-purity type-I collagen-based skin substitute (HPTC), e.g., Helicoll®, and dehydrated human amnion/chorion membrane (dHACM) are advanced wound therapies with promising results in previous single-centre studies. This multicentre randomized controlled trial compared the efficacy of HPTC versus dHACM added to standard of care (SOC) in treating chronic DFUs.

methodsA total of 120 patients with DFUs were enrolled across four medical centres in the state of Karnataka, India, and randomized to receive either HPTC (n=60) or dHACM (n=60) along with standard care. The primary outcome was the proportion achieving wound size reduction at four weeks of intervention and one week follow-up, with continuous wound-area monitoring during the treatment window. Secondary outcomes included histological assessment of vascular incursion and wound biology on day 5 (biopsy), time to complete wound closure, percent area reduction over time, number of repeat HPTC applications, adverse events/complications, patient-reported quality of life (QoL), and scar quality (Vancouver Scar Scale (VSS)). Statistical analyses used chi-square or Fisher's exact tests for categorical comparisons, t-tests/Mann-Whitney for continuous/ordinal outcomes, and two-sided alpha.

resultsHPTC demonstrated superior healing outcomes with a mean wound area reduction at five weeks, 81.5% ± 12.3 against 64.2% ± 14.1 in the dHACM group (p<0.001). Also, 88.3% (53 patients) of patients in the HPTC group achieved ≥50% wound reduction versus 55% (33 patients) in the dHACM group (p<0.001). Complete wound closure was achieved in 50 (83.3%) HPTC patients compared to 31 (51.7%) dHACM patients (p<0.001). Histological analysis revealed significantly enhanced vascular infiltration (2.4±0.6 vs 1.8±0.7, p<0.001), neo-epithelialization (2.6±0.5 vs 2.1±0.6, p<0.001), fibroblast activity (2.5±0.6 vs 1.9±0.7, p<0.001) and capillary density (45.6 ± 7.9 vs 29.4 ± 9.2 vessels/mm², p<0.001), in the HPTC group. Mean time to closure was 22.2 ± 5.4 days for HPTC versus 28.8±6.2 days for dHACM (p<0.001). Adverse incidence rates were low and similar between arms (HPTC - 6.7% vs dHACM 18.3%, with p = 0.095). Patient-reported QoL improved more in HPTC, especially with respect to resumption of daily activities and social functioning (p<0.001). Mean VSS scores at five weeks were better (lower) in HPTC (4.2±2.1) vs dHACM (6.8±2.8), p<0.001).

conclusionsIn this multicentre study based on a pooled design, HPTC (Helicoll) demonstrated statistically and clinically significant superiority versus dHACM over a four-week treatment period with one-week follow-up for DFUs in terms of percent area reduction, with enhanced cellular activity, faster healing times, and improved patient quality of life. The superior healing effect of Helicoll is attributed to its high-purity type I collagen composition, providing an optimal scaffold for cellular attachment and tissue regeneration. These results align with our prior single-centre experience with Helicoll, demonstrating faster and more complete healing of DFUs compared to dHACM, showing its potential as a more effective treatment option.