Zelen CM, Serena TE, Gould L, Le L, Carter MJ, Keller J, Li WW, et al.
International wound journal. Date of publication 2016 Apr 1;volume 13(2):272-82.
1. Int Wound J. 2016 Apr;13(2):272-82. doi: 10.1111/iwj.12566. Epub 2015 Dec 23.
Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a
prospective, randomised, controlled, multi-centre comparative study examining
clinical efficacy and cost.
Zelen CM(1), Serena TE(2), Gould L(3), Le L(4), Carter MJ(5), Keller J(6), Li
WW(7).
Author information:
(1)Professional Education and Research Institute, Roanoke, VA, USA.
(2)Serena Group, Cambridge, MA, USA.
(3)Department of Plastic Surgery, Wound Recovery Center, Kent Hospital, Warwick,
RI, USA.
(4)St. John Wound Care, Tulsa, OK, USA.
(5)Strategic Solutions, Inc., Cody, WY, USA.
(6)Shenandoah Lower Extremity Research, Troutville, VA, USA.
(7)The Angiogenesis Foundation, Boston, MA, USA.
Advanced therapies such as bioengineered skin substitutes (BSS) and dehydrated
human amnion/chorion membrane (dHACM) have been shown to promote healing of
chronic diabetic ulcers. An interim analysis of data from 60 patients enrolled in
a prospective, randomised, controlled, parallel group, multi-centre clinical
trial showed that dHACM (EpiFix, MiMedx Group Inc., Marietta, GA) is superior to
standard wound care (SWC) and BSS (Apligraf, Organogenesis, Inc., Canton, MA) in
achieving complete wound closure within 4-6 weeks. Rates and time to closure at a
longer time interval and factors influencing outcomes remained unassessed;
therefore, the study was continued in order to achieve at least 100 patients.
With the larger cohort, we compare clinical outcomes at 12 weeks in 100 patients
with chronic lower extremity diabetic ulcers treated with weekly applications of
Apligraf (n = 33), EpiFix (n = 32) or SWC (n = 35) with collagen-alginate
dressing as controls. A Cox regression was performed to analyse the time to heal
within 12 weeks, adjusting for all significant covariates. A Kaplan-Meier
analysis was conducted to compare time-to-heal within 12 weeks for the three
treatment groups. Clinical characteristics were well matched across study groups.
The proportion of wounds achieving complete closure within the 12-week study
period were 73% (24/33), 97% (31/32), and 51% (18/35) for Apligraf, EpiFix and
SWC, respectively (adjusted P = 0·00019). Subjects treated with EpiFix had a very
significant higher probability of their wounds healing [hazard ratio (HR: 5·66;
adjusted P: 1·3 x 10(-7) ] compared to SWC alone. No difference in probability of
healing was observed for the Apligraf and SWC groups. Patients treated with
Apligraf were less likely to heal than those treated with EpiFix [HR: 0·30; 95%
confidence interval (CI): 0·17-0·54; unadjusted P: 5·8 x 10(-5) ]. Increased
wound size and presence of hypertension were significant factors that influenced
healing. Mean time-to-heal within 12 weeks was 47·9 days (95% CI: 38·2-57·7) with
Apligraf, 23·6 days (95% CI: 17·0-30·2) with EpiFix group and 57·4 days (95%CI:
48·2-66·6) with the SWC alone group (adjusted P = 3·2 x 10(-7) ). Median number
of grafts used per healed wound were six (range 1-13) and 2·5 (range 1-12) for
the Apligraf and EpiFix groups, respectively. Median graft cost was $8918 (range
$1,486-19,323) per healed wound for the Apligraf group and $1,517 (range
$434-25,710) per healed wound in the EpiFix group (P < 0·0001). These results
provide further evidence of the clinical and resource utilisation superiority of
EpiFix compared to Apligraf for the treatment of lower extremity diabetic wounds.
© 2015 The Authors. International Wound Journal published by Medicalhelplines.com
Inc and John Wiley & Sons Ltd.
DOI: 10.1111/iwj.12566
PMID: 26695998 [Indexed for MEDLINE]
