Results From a Phase 2 Study Assessing the Safety and Efficacy of Bromelain-based Enzymatic Debridement Agent

In this video, Dr. John Lantis II shares the data from a recent study (Results From ChronEx: A Phase 2 Multicenter, Prospective, Randomized, Placebo-controlled, Adaptive Design Study Performed to Evaluate the Safety and Efficacy of Bromelain-based Enzymatic Debridement Agent in Debridement of Venous Leg Ulcers) that was presented at the 2023 SAWC Spring in National Harbor, Maryland.
 

Transcript: 

Hello. I'm John Lantis. I'm a vascular surgeon in New York City. And today, I'm going to be presenting to you a trial that we recently completed looking at the use of bromelain enzymatic debridement in patients with venous leg ulcers. This is a study that is a pre-market study looking at a patient population of 120 patients, all who had venous leg ulcers, with an interesting study design of being three ... It was a 3:3:2 study. In other words, 3 patients got active therapy; 3 patients got a placebo, which was the gel without the active agent (the bromelain, which is the active agent in this product in it); and then 2 patients would've gotten standard of care.

The patients who had the active agent and the placebo gel got up to 8 applications, basically 1 day apart. So in most cases, patients got therapy Monday, Tuesday, Wednesday, Thursday, and then, if they needed it, Monday, Tuesday, Wednesday, Thursday the next week. And then that was the cessation of it. There was a predefined interim analysis at 80 patients.

The primary endpoint was complete debridement of non-viable tissue of the active agent versus the gel vehicle. Secondary endpoints included pain, wound area reduction, granulation tissue, quality of life, and time to complete debridement.

This started with a one-week run-in period, then about 72 hours between the baseline and randomization, the active therapy over those 8 weeks, and then for 4 weeks after that ... I'm sorry. Those 8 visits, 8 visits over 2 weeks. I misspoke. Those next 2 weeks had 4 visits over that period of time, and then they went on and were followed out to an additional 12-week period. So relatively long follow-up for a very acute intervention.

There was a total enrollment of almost 200 patients, with 120 patients randomized. Forty-six patients got the active therapy, 43 patients got the gel vehicle, and 31 patients got the non-surgical standard of care. So those patients were not allowed to have sharp debridement.

All the patients were basically the same throughout the study. It is notable that the gel vehicle patients had slightly older and slightly larger wounds, but this was not statistically significant.

The highlight of this study is that the primary endpoint is as follows. Sixty-three percent of the patients, or that would be 29 of the 46 patients who got the active agent, were completely debrided within that period of time, that first 8 applications. Whereas for the gel vehicle, the gel without the bromelain in it, it was 13 of 43 patients, or a total of 30% of the patients. So again, 63% fully debrided within that 2-week period with the 8 applications versus 30%.

If you take a look at this slightly differently, of folks who had complete debridement versus for the non-surgical standard of care, only 4 patients reached complete debridement in that period of time. And the average number of applications was 3.6 or median of 4 applications for the active agent. So in other words, patients who were going to be fully debrided actually only took about a week to get fully debrided.

Also of note is the overall time. The median time to complete debridement for the active agent was 9 days, so 4 applications over 9 days, where for the non-surgical standard of care, it was approximately 60 days for most patients to get adequately debrided, and for those with a gel vehicle, similarly, it was 63 days. And again, 9 days for the active agent. So very rapid, full debridement of these patients.

In addition to this, we took a look at the patients who had good granulation tissue at the end of their treatment, and the idea was patients who had more than 75% of their wound bed being granulated was important. So those who were treated with the active agent, the bromelain, approximately 93% of those patients had adequate or excellent granulation tissue at the end of their debridement period. So it wasn't that you were just removing the bad and leaving behind nothing, but you were removing the bad and you were actually leaving behind good granulation tissue. The gel vehicle, in contrast, was only about 50% of the patients did we see good granulation tissue. And of note for those, there was a population that had 100% of their wound was granulated, so in other words, totally debrided and very well granulated. And that was 50% for the active agent and approximately 25% for the gel vehicle. So again, a very positive outcome for good granulation formation at the same time.

Then for the secondary endpoints, the study was not powered for any of these secondary endpoints. Of note, there was not a significant difference in pain between the gel vehicle and the bromelain product. And the nice portion about this is there is some concern that the bromelain product is so caustic it could cause pain. But there was no difference in pain between the placebo and the active agent.

The wound area within that 2-week period, not shockingly, did not change in size. Again, the primary endpoint was adequacy of debridement, not change in area of the wound. So the active agent and the gel were the same.

And quality of life did not change. Again, not very surprising due to the fact that the patient's wounds were roughly the same size as when they started, just much cleaner than they would've been otherwise.

There was some improvement in overall clinical signs of infection for the active agent. For the active agent, there were fewer clinical signs of infection at about a little bit less than 50%. And for the gel vehicle, they were questionable or possibly clinical signs of infection in about 70% of the patients. But again, this was really visual cues, nothing to do with actual bacterial burden, et cetera.

And then at the end of the day, there was not a very significant difference in time to closure of these wounds, as these were fairly discreet periods of time and just a single adequacy of debridement.

So in closing, the product was safe. It was well tolerated. It met its primary endpoint very well. You can see the pictures in the poster taking a look at the adequacy of debridement. And then in some cases where a patient got an autograft, for example, you can see a patient who's gone from an open wound to a completely closed wound. And that's one of the thoughts, is what should be done after this adequate debridement has occurred?

The results were consistent with the idea that VLU patients are going to do well with good debridement, but they may need something further. The future plan is a global phase 3 trial, which is being planned in conjunction with the FDA and European management. And that is hoping to start in Q4 of this year.

So thank you very much for taking a look at our poster, and I hope it brought some new perspectives to your wound care thought process.