Treatment of recalcitrant venous leg ulcers with autologous keratinocytes in fibrin sealant: A multinational randomized controlled clinical trial

Abstract

In a multicenter trial, the effect of a commercially available combination of autologous keratinocytes (3-6 x 10(6)/mL) with fibrin sealant (Tissucol Duo S Immuno, Baxter Hyland Immuno) on the healing of recalcitrant venous leg ulcers (duration >3 months) was compared with standard care. The primary endpoint was time to healing, and the secondary endpoint was number of healed ulcers in both groups. Both groups received compression therapy with short-stretch bandages. Forty-four (38.3%) of the 116 patients who had BioSeed-S treatment achieved complete healing of the target ulcer compared with 24 (22.4%) of 109 patients who received standard treatment. The advantage for treatment with BioSeed-S over standard treatment was statistically significant (chi-square test: p=0.0106). Time to complete healing of ulcers: the log-rank test for equality over strata revealed a superiority of treatment with BioSeed-S+compression (median: 176 days) over compression+standard care (median >201 days) (p<0.0001). This study, to date the largest multicenter study with autologous keratinocytes, provides evidence for its efficacy in the treatment of patients with therapy-resistant chronic venous leg ulcers.

Comparative effectiveness of advanced wound dressings for patients with chronic venous leg ulcers: A systematic review

“…We were unable to draw any meaningful conclusions on the effect of Dermagraft on CVUs because of an insufficient strength of evidence generated from the trials . Lastly, autologous keratinocytes in a fibrin sealant healed a significantly greater proportion of ulcers and achieved a shorter median time to complete wound closure over 26 weeks when compared with compression on ulcers following a 4‐week run‐in period of optimal conservative care …”

“…We included 37 studies (38 publications) enrolling a total of 3,990 patients (Figure ) . Thirty‐six of 37 studies were RCTs, one was a nonrandomized trial, and another was a retrospective cohort study.…”

Human cell therapy for venous leg ulcers

“…Differences in culture conditions and the use of various dermal components may account for differences in reported efficacy across the various single-cell and multi-cell autologous tissue constructs, but generally good results have been obtained using basic engineered tissue approaches [58][59][60][61] [60,62]. This product also showed good safety and efficacy, but the company filed for insolvency after failing to obtain necessary funding.…”

An Evaluation of the Association for the Advancement of Wound Care Venous Ulcer Guideline and Recommendations for Further Research

“…30 Mol et al 31 reported a case series of 5 patients in which allogeneic fibroblasts covered with autologous cultured keratinocytes led to improved cosmetic appearance in healed ulcers compared with punch grafts. One RCT demonstrated that more than 50% of venous leg ulcers healed completely when treated with autologous keratinocytes in a fibrin sealant.…”