In this research presentation, Dr. Robert J. Snyder reports on the results of an open phase 2 study assessing the safety, efficacy, and pharmacologic effects of bromelain-based enzymatic debridement product on biofilm and microbial loads in patients with diabetic foot ulcers and venous leg ulcers. Data were presented at the 2022 Symposium on Advanced Wound Care (SAWC) Fall.
This is part 1 of a 2-part interview. Part 2 can be found here.
Good morning. My name is Dr. Robert Snyder. I’m the Dean and Professor of Clinical Research at Barry University School of Podiatric Medicine. My topic today are results from an open phase 2 study assessing the safety, efficacy, and the pharmacologic effects of a bromelain-based enzymatic debridement product on biofilm and also microbiologic load in patients with diabetic foot ulcers and venous leg ulcers.
From an introductory standpoint, of course, debridement is the centerpiece of the wound bed preparation model. It’s considered a basic necessity, an inducing tissue repair. We also know that biofilm is very, very often problematic. 90% of all chronic wounds have biofilm, and we think that 100% of all diabetic foot ulcers have biofilm. Biofilm infection in wounds really is a major contributor to increasing morbidity, delayed healing, persistent infections, and certainly this leads to a much greater cost. The use of novel therapies that specifically remove necrotic tissue and reduced bioburden and promote biofilm dispersion is really a very promising strategy in improving patient outcomes.
Bromelain-based enzymatic breeding agents, which we’re now going to call BBD, is a product which is currently in clinical development for debride in nephrotic wounds. The study objectives here were not only to assess safety and efficacy, but also the pharmacologic effect in up to 15 patients with venous leg ulcers and diabetic foot ulcers. From a methodological standpoint, we looked at 12 diabetic foot ulcers and venous leg ulcers. They were enrolled in a perspective open-label, single-arm phase 2 study. Patients were treated with up to 8 applications of BBD, and then continued to be followed for 2 weeks. We did punch biopsies, 3-millimeter punch biopsies, before and after debridement. These punch biopsies were also used in combination with wound fluids to determine biomarkers.
Additionally, we used fluorescent imaging device to determine bacteria loads of anything greater than 10^4. We also wanted to see what type of bacteria may be present there. Additionally, it was very important for us to be able to see where the most robust bacteria were so that when we took the biopsies, we would take it in an appropriate place. Biopsy samples were examined by the Center for Biofilm Engineering in Bozeman, Montana, using a confocal scanning laser microscopy.
The results were really very elucidating. Seven diabetic foot ulcers and 3 venous leg ulcer patients completed the treatment, and in 8 out of 10 patients, 89% to a 100% non-viable tissue was removed within 2 to 8 applications. Additionally, an average reduction of 35% in wound size was measured at the end of 2 weeks when we did our 2-week follow up. In all patients that were positive for biofilm at baseline, the biofilm was reduced dramatically to single individual microorganisms, or not detected by the end of treatment, with an average biofilm score of 2.0 at a baseline versus 0.91 at the end of treatment.
Looking at the fluorescence testing, predominantly Staph aureus, we noted a reduction from 1.19 cm2 pre-treatment to 0.44 cm2 post-treatment. In 2 patients, we did see Pseudomonas, and we saw the reduction of 3.19 cm2 to 0. Safety data showed that BBD was safe and well tolerated. We did look at biomarkers as well relative to wound fluid, and we did not see any meaningful results there. Figure 1 really represents venous leg ulcers and diabetic foot ulcers before and after treatment. The bottom were taken, again, from 3 subjects. Photos on the bottom were taken post-treatment after 5, 8, and 2 daily treatments.
Looking at Figure 2, we looked at wound biopsies and, again, we took the biopsies pre-debridement before we utilized the application of the bromelain and then after complete debridement. Wound debridement, pre- and post-treatment, from 2 representative wounds were shown here, and the pre-treatment biopsy sections were ranked with biofilm scores of 5. This was really thick, very viscous, continuous film of microorganisms. As you can see, and very, very significantly, this number was ranked at 1 at the end of treatment, which meant that there was either a single organism, which really is considered negative for biofilm.
Looking at Figure 3, we looked at fluorescent imaging from 2 representative wounds demonstrating that bacterial load on the wound pre- and post-treatment were dramatically different. The wound on the left side, the fluorescence area was reduced from 0.84 cm2 to 0.2 cm2 post-treatment. On the right, fluorescent was reduced from 7.08 cm2 to 0. We have concluded that the data shows here that BBD is safe and can effectively debride wounds while promoting wound area reduction, [and] reducing biofilm and bacterial burden. I thank you very much for your time.
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