Journal of Vascular Surgery : Venous and Lymphatic Disorders

Objective: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials. Methods: Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm to 12 cm in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm and #36 cm with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure. Results: This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < . 10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < . 05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987]). Conclusions: Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis. (J Vasc Surg: Venous and Lym Dis 2017;5:829-36.) Venous leg ulcers (VLUs) represent a large and growing burden to the U.S. health care system. The prevalence of VLUs in the United States is estimated at 1% to 2% and is expected to increase as we live longer. The cost to the U.S. health care system associated with VLU care is estimated to be in excess of $2.5 billion annually. Treatment of VLU remains challenging. Even with optimal he Division of Vascular Surgery, University of North Carolina School edicine, Chapel Hill; the Division of Vascular Surgery, Section of nd Healing and Tissue Repair, University of Illinois Hospital and h Sciences System, and the Division of Plastic Surgery, Northern University Feinberg School of Medicine, Chicago; the Division scular and Endovascular Surgery, Mt. Sinai West and St. Luke’s Hos, New York; the Department of Dermatology and Cutaneous SurMiller School of Medicine, University of Miami, Miami; the rsity of Freiburg, Freiburg; the Department of Dermatology, Univerf Cologne, Cologne; the Przychodnia Lekarsko-Podologiczno Rehacyjna PODOS, Warsaw; and the Smith & Nephew, Inc, Graduate ol of Biomedical Sciences, University of North Texas Health Science er, and the Department of Pediatrics, University of North Texas h Science Center, Fort Worth. embers of the HP802-247 Study Group are listed in the Appendix ne only). ical trials that serve as the basis for the data reported in this work were d by Smith & Nephew Inc. The Corporation supported the statistical sis for the study, but the study authors performed the analysis and conservative treatment, only 50% to 75% of VLUs will close within 6 months, and of these, 6% to 27% will recur annually. Thus, a substantial proportion of VLUs will become chronic. Currently, it is often difficult to predict which ulcers will fail to heal with current recommended treatment protocols for VLUs. Most previous reports have been based on limited data sets of fewer than interpretation and authorized the final decision to submit the manuscript