EpiFix Trumps Alternatives for Diabetic Foot Ulcer Wounds

Pam Harrison

December 01, 2014

Wound healing in patients with diabetic ulcers is better with weekly applications of a dehydrated human amnion/chorion membrane allograft (EpiFix, MiMedx Group, Mariette, Georgia) compared with either a tissue-engineered skin substitute (Apligraf, Organo-genesis, Canton, Massachusetts) or standard wound care, a new randomized prospective trial shows.

The healing was markedly faster, more complete, and cheaper with EpiFix, said lead author of the study, Dr Charles Zelen (Professional Education and Research Institute, Roanoke, Virginia).

"Studies have shown that the longer a diabetic foot ulcer remains open, the more likely the ulcer is going to get infected and [that] the patient is going to lose their limb," Dr Zelen told Medscape Medical News.

"So you want to choose a product that is going to heal the fastest, and we've been able to show in this study and in our prior studies that the healing rate with EpiFix is greater than 90%. More important, it will heal the majority of wounds in an average of just over 2 weeks. I would…say that EpiFix is the treatment of choice for diabetic ulcers."

The study was published online November 26, 2014 in the International Wound Journal.

Asked to comment, Dr Matt Garoufalis (Veteran's Affairs Hospital, Chicago, Illinois), who was not involved in this study, told Medscape Medical News that the findings answer a lot of questions as to how EpiFix compares with older methods of treatment.

EpiFix "has really only come to the forefront in the past few years," Dr Garoufalis explained, "so this study…helps us understand that it is certainly very effective — often more effective than some of the tools that we have been using."

He also stressed how important it is to achieve rapid wound healing in patients with diabetic ulcers. "The longer these wounds stay open, the more morbidity and mortality these patients face, and we know that once we begin the amputation cycle, it leads to a shortened life span. So if we have tools and products that we can use that close these wounds faster and increase a patient's quality of life, then we are on the right track," he noted.

EpiFix is not the only amniotic-tissue product around — there are others in development that could be tested in diabetic foot ulcers, said Dr Zelen, and a trial of a new cryopreserved umbilical-cord allograft for diabetic foot ulcers has also recently begun.

First Comparative-Effectiveness Study of Two Wound-Care Products

In their paper, Dr Zelen and colleagues note that their study is the first multicenter randomized comparative-effectiveness study examining, side by side, the performance, outcomes, and utilization of two approved advanced wound-care products (Apligraf and EpiFix) as a treatment for chronic lower-extremity diabetic ulcers.

A total of 65 patients were initially entered into a 2-week run-in period, and 60 were eventually randomized to weekly treatment with Apligraf, EpiFix or standard wound care with collagen-alginate dressing, with 20 in each group.

Participants were seen by the investigator at the study site at least once every 7 days for up to 12 weeks or until 1 week after complete healing of the ulcer, whichever occurred first.

Those whose wounds failed to reduce by at least 50% after 6 weeks of study enrollment were withdrawn from the study to seek alternative care.

At each study visit, patients underwent ulcer debridement if required and cleansing with a sterile normal saline solution. The ulcers were also measured and photographed and wound surface area calculated to evaluate treatment response.

The primary objective of the study was to compare the percentage of wounds that had healed completely after 4 and 6 weeks of treatment.

At 4 and 6 weeks, complete wound healing occurred in a significantly greater percentage of patients treated with EpiFix compared with the other two modalities.

Treatment Complete healing: 4 wk (%) Complete healing: 6 wk (%) P (vs EpiFix)
EpiFix 85 (17/20 patients) 95 (19/20 patients)  
Apligraf 35 (7/20 patients) 45 (9/20 patients) < .003
Standard wound care 30 (6/20 patients) 35 (7/20 patients) < .003

All 20 patients in the EpiFix group exited the study within 6 weeks; 19 had healed completely and one was withdrawn from the study after 1 week because of an adverse event. Four of the 20 Apligraf patients exited the 12-week study unhealed — of these, three were withdrawn after 6 weeks with less than 50% healing and one left the study after 12 weeks unhealed. For those receiving standard care, 11 were withdrawn after 6 weeks due to failing to heal by at least 50%.

Lower Costs With EpiFix

Healing rates were also significantly faster with EpiFix (P < .0.0001), with an estimated median healing time of 13 days for those receiving EpiFix compared with 49 days both for those receiving Apligraf and those receiving standard wound care.

Investigators also estimated the amount of product used over the study period for each of the two product-based treatment groups.

Calculations revealed that a total of 5456 cm2 of Apligraf was used to cover a cumulative wound area of 158.6 cm2 for all patients in this group, and approximately 97% of the product was discarded.

In contrast, only 154 cm2 of EpiFix was used to cover a cumulative wound area of roughly the same size (154 cm2) for all patients in this group, and about 56% of the product was discarded.

The cost of the EpiFix product was therefore much lower at $1669 per patient compared with $9216 per patient for Apligraf.

As Dr Zelen observed, when Apligraf came out about 15 years ago, it was the product of choice for the treatment of wounds.

However, "technology has advanced considerably since then," he noted. For example, Apligraf — which is a skin product — is only good for a very short period of time, and it is temperature sensitive so it has to be carefully stored.

"New products like EpiFix have a shelf life of up to 5 years, and it comes in a small peel pack, so is easier to ship and arrives ready to go…in size-specific pieces so there is minimal to no wastage," he explained. "So…it's the most cost-effective product too, because you are not wasting any graft."

Apligraf, in contrast, comes in large pieces, which Medicare and other insurers insist be used on only one patient, discarding the rest.

Other Products in the Pipeline

At least one other amniotic-tissue product, AmnioFix, from the same company that markets EpiFix (MiMedx Group) has been tested in the treatment of plantar fasciitis in the foot and shown to be effective, Dr Zelen said.

In July, another company, Amniox Medical, said it had begun a multicenter, randomized study in which its cryopreserved umbilical-cord allograft (NEOX CORD 1K) will be compared with standard care in nonhealing diabetic foot ulcers.

This particular product differs from EpiFix in that its matrix is made up of both amniotic membrane and umbilical-cord tissue, but the principle behind the allografts is similar — both are designed to deliver proteins, cytokines, and growth factors to modulate inflammation and promote regeneration of normal tissue.

The growth factors and cytokines embedded in products such as EpiFix are key, says Dr Zelen, as they slow down the formation of scar tissue as well as helping the wounds heal faster.

"These are very exciting data for us and I think it's going to have a really large impact on the entire country in regard to the choices we now have for diabetic wounds," he concluded.

The study was sponsored and funded by MiMedx Group. Dr. Zelen reported he has no relevant financial relationships; the Professional Education and Research Institute of which he is medical director received funding for completion of the study and his role as principal investigator. Disclosures for the coauthors are listed in the article. Dr Garoufalis reported he has no relevant financial relationships.

Int Wound J. Published online November 26, 2014.Article

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