Fish Skin Graft vs Standard of Care in the Management of Chronic Diabetic Foot Ulcers: Long-Term Durability and Time to Heal

Editorial Board Member Dr. Stephen Bergquist interviews Dr. Eric J. Lullove about his original research article, “Final Efficacy and Cost Analysis of a Fish Skin Graft vs Standard of Care in the Management of Chronic Diabetic Foot Ulcers: A Prospective, Multicenter, Randomized Controlled Clinical Trial.”

Transcript

Stephen Bergquist:

Hey, good day everybody. I'm Steve Bergquist, Medical Doctor and Wound Care Physician in the Tennessee area. Happy to be sort of guiding some of this discussion today on a very interesting subject.

Dr. Eric Lullove:

So, hi everybody. I am Dr. Eric Lullove. I am a Foot and Ankle Podiatrist, Wound Care Specialist based in Coconut Creek, Florida. So for those of you not knowing where that is, I'm about an hour north of Miami.

Stephen Bergquist:

The long-term durability of the closure. So you had 6 months follow-up, 1 year follow-up, and what could you say about that?

Dr. Eric Lullove:

So the long-term durability I thought was really amazing. What we found was that majority of the patients stay closed. The majority of the patients really did not have recurrence. And I thought that was a big part of what we were doing with the long-term follow-ups was that we just basically kind of put them in orthotics and had their diabetic shoes, and that the majority of these patients were healed by 12 weeks, or that the proportional index of wounds were healed by 12 weeks. It's one thing to heal a patient, it's another thing to keep them closed. Because we know the data, what happens when they have a recurrence. The incidence of recurrence is that patients with a diabetic foot ulcer, 50% are going to have a recurrence within, you know the data better than I do, 3 to 5 years are going to have another one.

And we know what happens at that point going forward. God forbid they need a hospitalization and an amputation, that's a whole other issue. So I think if we take a bigger proactive approach with making sure the patients are followed up appropriately. Just like when a patient loses their leg and has a BK [below-knee] amputation and they get the proper prosthetic, they can have a functional life. But they got to use the prosthetic, otherwise they're sitting in a wheelchair the whole day and now you got other issues.

Stephen Bergquist:

So the study was well-designed that it is hitting these issues that we're talking about and may be boring to some people, but these are real-life issues that make this a realistic study. So there's primary, secondary, and tertiary outcomes. You're looking at primary, just wound healing at 12 weeks. You're looking secondary outcomes, which is time to heal. And the tertiary outcomes was the recurrence we just talked about. So I like that this study functioned into those pieces of puzzle. Don't really have to spend much time there, but the details did get looked at.

Dr. Eric Lullove:

Yeah. So one of the biggest things that obviously in any clinical trial and we look at percent area reduction. Is the product working in the trial that we expect it to? And one of the things that everybody should take home from our discussion today was that what we found with fish skin graft was that you didn't see it working so quickly weeks 1 to 2, or even 2 to 3. Where we really saw the big jumps were weeks kind of like 3 to 6. That was the big jump in patients responding to the applications on the tissue. So we kind of pushed out the percent area reduction to 6 weeks because that's what the data was showing us, which was showing us that at 6 weeks we had a mean percent area reduction of almost, I think 51.6%, at 6 weeks. And in that was in the collagen alginate arm, that was at [51.6]% in the standard of care arm. And then in the fish skin graft arm, it was 72.6%.

Stephen Bergquist:

So I've encircled that. It was important to me.

Dr. Eric Lullove:

Right. What we did show was that you can still use collagen alginate therapy with offloading, and you're still going to get better results than alone. But now when you apply advanced therapy with offloading, you're still surpassing standard-of-care therapy. And if you ask any patient, If I can heal your wound 20% faster, 20% more in the same amount of time by using cellular tissue products, they're going to say, "Yeah, use the cellular tissue product." And that's what we found. And the argument behind the paper was to show this to the commercial payers so that they get off of this old idea that what we do doesn't work, or they don't know what we're doing. And trying to make this argument that, "Listen, get on board with the science, get on board with the technology that we have available now 'cause we're proving it."

Stephen Bergquist:

So I loved it. So there is one little thing I want you to discuss because if you've got a reader who's looking for details and you know how our brains work, we look for the things that are wrong and try to fix. We don't notice necessarily all the things that are beautiful, we're always trying to fix. Well, page 74 on the article at the bottom there. When we look at the Mann-Whitney testing and looking at the difference, and I think this is what you were just talking about just now, if I'm clarifying, that if we want to look at those 2 to 6 weeks, we're not seeing a difference. The difference comes after, and that's what that paragraph is about.

Dr. Eric Lullove:

That's exactly what this was. That's what the data was showing us, that literally you don't see anything initially, and I think this is pretty much the similar argument for most of the tissues in this group, is that it takes the body some time, especially in our diabetic populations, to overcome the internal biology of just lack of forming an immune response. That these patients have an autoimmune disease already, they're already autoimmune-deficient, they're already inflammatory-mediated, they've got cytokines and all the other stuff that's inhibiting their healing that we have to overcome before we can see the benefit of these tissues. So it's easy to say, "Oh, it's not working in 2 weeks, we need to switch." And I would tell physicians, "No, stay the course, because you will see a result."