IN.PACT BTK: Step in the Right Direction for DCB in Below-Knee CLI

Patrice Wendling

October 20, 2020

An investigational drug-coated balloon (DCB) may offer clinical benefit in critical limb ischemia patients with below-the-knee (BTK) chronic total occlusions, preliminary results from the IN.PACT BTK study suggest.

Use of the IN.PACT 0.014 DCB (Medtronic) was associated with a numerically lower rate of late lumen loss than percutaneous transluminal angioplasty (PTA) at 9 months (mean, 0.89 vs 1.31 mm; P = .070).

The investigators, however, took a page from coronary studies, also assessing late lumen loss along the entirety of the lesion, rather than just at the single narrowest segment in the lesion, as is classically done.

Subsegmental late lumen loss proved significantly lower with the DCB than with PTA (mean, 0.59 vs 1.26 mm; P = .017).

"The subsegmental measurements are more rigorous," lead investigator Antonio Micari, MD, University of Messina, Italy, said at the virtual meeting of Transcatheter Cardiovascular Therapeutics (TCT) 2020. "This can provide more detail on how the lesion fails over time."

There is a relative paucity of DCB technology for BTK lesions, with three earlier DCB trials failing to meet their primary end point. Medtronic also withdrew its earlier-generation paclitaxel-coated IN.PACT Amphirion DCB from the global market in 2013 based on results from the IN.PACT DEEP trial showing a lack of treatment effect and trend toward more major amputations at 12 months.

The present results showed no safety concerns among the 50 participants, including no major amputations in either group and a low all-cause death rate of 4.3% for DCB and 8.0% for PTA (P = 1.0), Micari said.

The safety end point — a composite of freedom from device- and procedure-related death through 30 days, freedom from major target limb amputation within 270 days, and freedom from clinically driven target lesion revascularization within 270 days — was met by 91.3% of the DCB group and 87.5% of the angioplasty group (P = 1.0).

"That was a very interesting presentation with very promising results, but I'm not convinced," session comoderator and limb salvage pioneer Frank J. Veith, MD, said. "Are you planning to add more patients, and what about longer follow-up?

"I would be more convinced if you had 2-year follow-up and at least double or triple the number of patients in each arm," added Veith, professor of surgery at NYU Langone Health, New York City, and at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

Micari said they are planning longer follow-up, possibly out to 5 years. "This is a feasibility study and we are happy to show that, even in a small population, we have a difference. This is a new design of the study that we can apply to a larger trial and we are definitely looking for a bigger trial."

During a press briefing, discussant Peter A. Schneider, MD, University of California, San Francisco, said IN.PACT BTK is notable for several reasons: every person had a CTO and the mean lesion length was over 20 centimeters (DCB 21.5 cm vs PTA 21.8 cm). "So this is real-world stuff in a randomized fashion, but real-world lesions we take care of on a day-to-day basis.

"I really like the idea of the subsegmental late lumen loss analysis because the classic late lumen loss is great for coronaries, where you have short lesions, but in a 20-centimeter lesion, to really understand what's going on, the subsegmental makes a lot of sense," he said.

Additionally, functional duplex ultrasound was used on the table to ensure the "PTA group was not given short-shrift" and balloon angioplasty was optimized as the comparator, which supports that this was a real signal from, albeit a smaller-sized randomized trial, Schneider said.

"This is really another indication that, in fact, the potential for biologic therapy in the BTK arteries is something that feels like it's right around the corner," he said. "We've been working on it for so long but it feels imminent to me and this looks very promising."

Fellow discussant Robert Lookstein, MD, Ichan School of Medicine at Mount Sinai, New York City, commended Medtronic for going back to the drawing board to address the unmet need in critical limb ischemia, and agreed that these were very complex, real-world lesions.

Indeed, 87% of the DCB group and 89% of the PTA group had Rutherford grade 5 ischemia by site report, and 25% and 28%, respectively, had Trans-Atlantic Inter-Society Consensus Document (TASC) II grade D lesions by core lab assessment.

"My concern is that this is a small randomized trial," Lookstein said. "It's not clear to me that subsegmental late lumen loss is an appropriate end point for a Rutherford 5 cohort."

"I certainly think it brings up a lot of interesting questions about trial design," he said. "I agree that we are probably going to have an effective drug-coated balloon in the not-so-distant future. This is one step in the right direction, but there are still a lot of questions that need to be answered, especially if we're addressing patients with active wounds."

Asked what late lumen loss means to patients and whether the observed difference is enough to justify using a drug-coated balloon, Micari said more data are needed. "We will see, hopefully, in larger trials if this has an indication in the clinical field."

No one is going to use a device because of the presence or absence of late lumen loss, observed Schneider. "To me, both of these numbers — the class late lumen loss and the subsegmental lumen loss — are saying that there was an effect of medication, at least that's my interpretation."

The trial was funded by Medtronic.

Transcatheter Cardiovascular Therapeutics (TCT) 2020. Presented October 18, 2020.

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