Baseline factors affecting closure of venous leg ulcers

HP802-247 Study Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 cm2 to 12 cm2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm2 and ≤36 cm2 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.

Original languageEnglish (US)
Pages (from-to)829-835.e1
JournalJournal of Vascular Surgery: Venous and Lymphatic Disorders
Volume5
Issue number6
DOIs
StatePublished - Nov 1 2017

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Varicose Ulcer
Leg Ulcer
Wounds and Injuries
Diabetes Mellitus
Glycosylated Hemoglobin A
Leg
Body Mass Index
Therapeutics
Phase III Clinical Trials
Cell- and Tissue-Based Therapy
Keratinocytes
Ankle
Ulcer
Randomized Controlled Trials
Fibroblasts
Placebos
Regression Analysis
Confidence Intervals
Control Groups
Growth

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Baseline factors affecting closure of venous leg ulcers. / HP802-247 Study Group.

In: Journal of Vascular Surgery: Venous and Lymphatic Disorders, Vol. 5, No. 6, 01.11.2017, p. 829-835.e1.

Research output: Contribution to journalArticle

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title = "Baseline factors affecting closure of venous leg ulcers",
abstract = "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 cm2 to 12 cm2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm2 and ≤36 cm2 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.",
author = "{HP802-247 Study Group} and Marston, {William A.} and Ennis, {William J.} and Lantis, {John C.} and Robert Kirsner and Galiano, {Robert D.} and Wolfgang Vanscheidt and Eming, {Sabine A.} and Marcin Malka and Cargill, {D. Innes} and Dickerson, {Jaime E.} and Slade, {Herbert B.} and Andersen, {Charles A.} and Anderson, {Caesar A.} and Petr Arenberger and Roland Aschoff and Matthias Augustin and Noemi Bakos and Hilde Beele and An Bervoets and Joseph Cavorsi and Cazzell, {Shawn M.} and Petra Cetkovska and Clements, {J. Randolph} and Cook, {Emily A.} and Deck, {Kenneth B.} and {De Conninck}, Arlette and Despatis, {Marc A.} and Dhillon, {Yadwinder S.} and Joachim Dissemond and Cyaandi Dove and Steffen Emmert and Enriquez, {George L.} and Alik Farber and Olga Filipovska and Frykberg, {Robert G.} and Gagnon, {Joel J.} and Tobias George and Vincent Giacalone and Gordon, {Ian L.} and Tomasz Grzela and Csaba Hajdu and Hanft, {Jason R.} and Bernhard Homey and Hood, {Douglas B.} and Thomas Horn and Jimenez, {Juan C.} and Michael Juenger and Keast, {David H.} and Lajos Kemeny and Kim, {Paul J.}",
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TY - JOUR

T1 - Baseline factors affecting closure of venous leg ulcers

AU - HP802-247 Study Group

AU - Marston, William A.

AU - Ennis, William J.

AU - Lantis, John C.

AU - Kirsner, Robert

AU - Galiano, Robert D.

AU - Vanscheidt, Wolfgang

AU - Eming, Sabine A.

AU - Malka, Marcin

AU - Cargill, D. Innes

AU - Dickerson, Jaime E.

AU - Slade, Herbert B.

AU - Andersen, Charles A.

AU - Anderson, Caesar A.

AU - Arenberger, Petr

AU - Aschoff, Roland

AU - Augustin, Matthias

AU - Bakos, Noemi

AU - Beele, Hilde

AU - Bervoets, An

AU - Cavorsi, Joseph

AU - Cazzell, Shawn M.

AU - Cetkovska, Petra

AU - Clements, J. Randolph

AU - Cook, Emily A.

AU - Deck, Kenneth B.

AU - De Conninck, Arlette

AU - Despatis, Marc A.

AU - Dhillon, Yadwinder S.

AU - Dissemond, Joachim

AU - Dove, Cyaandi

AU - Emmert, Steffen

AU - Enriquez, George L.

AU - Farber, Alik

AU - Filipovska, Olga

AU - Frykberg, Robert G.

AU - Gagnon, Joel J.

AU - George, Tobias

AU - Giacalone, Vincent

AU - Gordon, Ian L.

AU - Grzela, Tomasz

AU - Hajdu, Csaba

AU - Hanft, Jason R.

AU - Homey, Bernhard

AU - Hood, Douglas B.

AU - Horn, Thomas

AU - Jimenez, Juan C.

AU - Juenger, Michael

AU - Keast, David H.

AU - Kemeny, Lajos

AU - Kim, Paul J.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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 cm2 to 12 cm2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm2 and ≤36 cm2 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.

AB - 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 cm2 to 12 cm2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm2 and ≤36 cm2 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.

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DO - 10.1016/j.jvsv.2017.06.017

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VL - 5

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JO - Journal of Vascular Surgery: Venous and Lymphatic Disorders

JF - Journal of Vascular Surgery: Venous and Lymphatic Disorders

SN - 2213-333X

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