Clinical Studies
Safety
Dermavest tissue is obtained from normal, healthy, full-term pregnancies delivered in Unites States. Donors have consented to transfer of the tissue to third parties. Each donor is carefully screened. Comprehensive medical and social histories of the donors are obtained and placentas with attached umbilical cord and amnion are procured, processed, and tested in accordance with standards established by the American Association of Tissue Bank (AATB) and the FDA to minimize potential risks of disease transmission to recipients. In addition to AATB and FDA requirements, every lot of Dermavest is tested for biocompatibility according to ISO 10993 standards and in the over 7 years Dermavest has been on the market it has never generated even a single adverse event.
Efficacy
Attached are eleven comprehensive and accepted studies regarding wound healing using human, placental tissue-based products. Two of the eleven studies were completed prior to the introduction of Aedicell's Dermavest technology to the market. These studies conclusively depict the effectiveness of human, placental tissue-based products for the treatment of wounds when compared to standard of care (SOC) in a variety of indications and settings.
When Dermavest treatment is compared to these same chronic ulcer populations treated with standard of care, a similar confidence of efficacy is in evidence.
1. In the Journal of Regenerative Engineering and Translational Medicine, Grande et al. were able to show that with the use of Dermavest there is exhibited enhanced collagen synthesis and accelerated wound healing in a diabetic rat model1.
2. Diabetic Ulcer
In the paper by Snyder et al 2 it was shown that, in the treatment of 250 diabetic ulcer patients by standard of care, for those patients who at 4 weeks of treatment exhibited a percent area reduction (PAR) in wound size of 50%, there was a significant correlation for complete healing by 12 weeks over those patients whose PAR was less than 50% at week 4 of treatment. Famously, this study led to the establishment of the 4-week standard of care "run in" required by Medicare treatment algorithms prior to the utilization of advanced therapies.
Because placental based tissue products contain similar raw material constituents, to compare the efficacy of these different therapies directly is difficult. But by utilizing data that reflects the percent of patients who reach a 50% reduction in wound size at 4-weeks as a metric (PARM50), we can determine the efficacy of these advanced therapies over standard of care. We can then use the confidence (p-value) of these comparisons to check if a therapy, due to perhaps its manufacturing process drastically reducing the availability of valuable proteins and growth factors, is not as strongly efficacious over standard of care as the others. For example, the results (table 1) obtained from two peer reviewed posters on the treatment of Diabetic ulcers with Dermavest 3,4 show a similar confidence (p value) in improvement of PARM50 over standard of care to two other human tissue-based products. When combining data from two case study posters presented at the Society of Advanced Wound Healing conferences in the Spring of 2015 and 2016, Dermavest® and Plurivest® evidenced the following:
When combining data from two case study posters presented at the Society of Advanced Wound Healing conferences in the Spring of 2015 and 2016, Dermavest® and Plurivest® evidenced the following:
Notes:
a) All the p-values for the advanced treatment arms including the Dermavest arm are close to or under 0.05 which translates to a 95% confidence that one can be 95% confident the advanced treatment arms will enable more patients to have a PAR > than 50% at week 4 which in turn correlates to complete healing at week 12.
b) While the sample size for the advanced treatment arms are only 10 to 20, the statistics take this into account and the statistical difference is real.
c) It should be noted the starting wound size for the Dermavest arm was on average over 170% greater than the starting wound size of the other two advanced treatment arms.
3. Venous Ulcer
Similar to the paper by Snyder et al.2, Gelfand and his team7 established a metric for venous ulcer treatment by which the patients who achieve a PAR of 40% at 4 weeks correlates significantly with 12- and 24-week healing. Serena et al.8 expound on the PARM40 as a metric that correlates with 24-week healing by retroactively examining the results from their prospective, randomized controlled clinical study comparing the treatment of venous ulcers between standard of care and Epifix, a human placental tissue based skin substitute9.
As we did with the diabetic ulcer studies, in table-2 we compare the confidence (p value) in the improvement in PARM40 over standard of care between Dermavest3,4 and Epifix, a human placental based tissue product.
Discussion
In many retrospective and prospective clinical studies human placental tissue-based products have been shown to be more effective for the healing of chronic ulcers than standard of care.
All of the human placental tissue-based products for wounds (grafts) are regulated as 361 human/cellular tissue products (H/CTP's) and as such are required by the FDA to be minimally manipulated so as to retain their natural elements. As is to be expected, it has been shown in two studies that the improvement in efficacy over standard of care when using Dermavest is the same as two other human based tissue products. Having established equivalent efficacy, the value propositions that Dermavest holds over otherhuman tissue-based products come to the fore: its ease of use; room temperature storage requirements, its density (5x tissue per square cm of amnion only grafts) and its ability to spread to cover much larger wound areas less expensively.
References
1. Schwartz, J., Koutsoumbelis, S., Parikh, Z. et al. The Use of Human Amnion/Chorion for the Enhancement of Collagen Synthesis and Acceleration of Wound Healing in a Diabetic Rat Model. Regen. Eng. Transl. Med. 7, 41–46 (2021).
2. Snyder RJ, Cardinal M, Dauphinée DM, Stavosky J. A post-hoc analysis of reduction in diabetic foot ulcer size at 4 weeks as a predictor of healing by 12 weeks. Ostomy Wound Manage. 2010 Mar 1;56(3):44-50.
3. James McGuire DPM, PT, LPED, FAPWHc, Joshua Sebag BA. New Placental Acellular Tissue Product in the Management of Chronic Wounds: A Case Series. Poster presented at: Symposium on Advanced Wound Care; April 13th, 2016; Georgia World Congress Center in Atlanta, Georgia
4. Heather Connell CCRP, Raphael Yaakov, Keyur Patel DO, Daniel DiMacro DO, Lam Le MD, Bryan Doner D0, Laura Serena LPN, Debbie Meyers LPN, Lindsay Saunders, Sharon McConnell CCRC, Thomas Serena MD. Human Placental Connective Tissue Matrix in the Treatment of Chronic Wounds: A Prospective Multi-Center Case Series. Poster presented at: Symposium on Advanced Wound Care; October 16, 2014; Caesar’s Palace in Las Vegas, Nevada
5. Zelen CM, Serena TE, Denoziere G, Fetterolf DE. A prospective randomized comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers. Int Wound J. 2013 Oct;10(5):502-7.
6. Zelen CM, Gould L, Serena TE, Carter MJ, Keller J, Li WW. A prospective, randomized, controlled, mulit-center comparative effectiveness study of healing using dehydrated human amnion/ chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J. 2014;11(2):122–128
7. Gelfand JM, Hoffstad O, Margolis DJ. Surrogate endpoints for the treatment of venous leg ulcers. J Invest Dermatol. 2002 Dec;119(6):1420-5.
8. Serena TE, Yaakov R, DiMarco D, Le L, Taffe E, Donaldson M, Miller M. Dehydrated human amnion/chorion membrane treatment of venous leg ulcers: correlation between 4-week and 24-week outcomes. J Wound Care. 2015 Nov;24
9. Serena TE, Carter MJ, Le LT, Sabo MJ, DiMarco DT; EpiFix VLU Study Group. A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair Regen. 2014 Nov-Dec;22
10. Haugh AM, Witt JG, Hauch A, Darden M, Parker G, Ellsworth WA, Buell JF. Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis. Plast Reconstr Surg Glob Open. 2017 Apr 25;5(4)
11. Smiell JM, Treadwell T, Hahn HD, Hermans MH. Real-world Experience With a Decellularized Dehydrated Human Amniotic Membrane Allograft. Wounds. 2015 Jun;27(6):158-69
12. Regulski M, Jacobstein DA, Petranto RD, Migliori VJ, Nair G, Pfeiffer D. A retrospective analysis of a human cellular repair matrix for the treatment of chronic wounds. Ostomy Wound Manage. 2013 Dec;59(12):38-43
13. Snyder RJ, Shimozaki K, Tallis A, Kerzner M, Reyzelman A, Lintzeris D, Bell D, Rutan RL, Rosenblum B. A Prospective, Randomized, Multicenter, Controlled Evaluation of the Use of Dehydrated Amniotic Membrane Allograft Compared to Standard of Care for the Closure of Chronic Diabetic Foot Ulcer. Wounds. 2016 Mar;28(3):70-7
14. Zelen CM, Orgill DP, Serena TE, Galiano RD, Carter MJ, DiDomenico LA, Kaufman JP, Keller J, Young NJ, Li WW. Human Reticular Acellular Dermal Matrix in the Healing of Chronic Diabetic Foot Ulcerations that Failed Standard Conservative Treatment: A Retrospective Crossover Study. Wounds. 2017 Feb;29(2):39-45