Second-Generation Chocolate Touch DCB Bests Lutonix for Patency in PAD

WASHINGTON, DC—In PAD patients, treatment with a second-generation paclitaxel drug-coated balloon (DCB) led to better target vessel patency and less repeat revascularization in a head-to-head comparison with a first-generation DCB, the CHOCOLATE TOUCH study found.

“These results support the safety and efficacy of the Chocolate Touch DCB for the treatment of symptomatic patients with superficial femoral artery disease,” Mehdi Shishehbor, DO, MPH, PhD, (University Hospitals of Cleveland. OH), the study’s lead author, reported here in a late-breaking trial session at the American College of Cardiology (ACC) 2022 Scientific Session.

The Chocolate Touch DCB (TriReme Medical) has an over-the-wire design in which the paclitaxel-coated balloon catheter and dilation component are mounted on a nitinol structure that separates the inflated balloon into small sections. Once expanded, the balloon takes on the appearance of a row of little pillows. This feature, the investigators say, increase the surface area of the balloon by about 20% and may allow more drug delivery at the time of intervention as well as helping to limit vessel damage and minimize the occurrence of dissections.

Shishehbor and colleagues say they are unsure exactly what advantage Chocolate Touch provides that accounts for the better outcomes compared with Lutonix, but add that it also has a higher dose of paclitaxel (3 µg/mm² vs 2 µg/mm²).

“To me, this is very hypothesis-generating to say we saw a benefit. Now the question is why,” panelist Geoffrey Barnes, MD (University of Michigan, Ann Arbor), told TCTMD following the presentation. “Is it the dose of the drug? Is it the increased surface area because of the design of the balloon? We need to understand what was driving the difference, so we will know how to iterate on that going forward.”

With standard DCBs, concerns have been raised amount the varying amounts of drug and particulate that are lost as the DCB goes from package to patient. Going forward, Barnes said it will be important to elucidate whether the advantage of Chocolate Touch is related to the dose of the drug that's on the balloon or the dose that actually gets to the lesion.

The study was simultaneously published in Circulation.

Patency and Mortality Addressed

Chocolate Touch randomized 313 patients (mean age 69.4 years; 57.5% male) with intermittent claudication or ischemic rest pain (Rutherford category 2-4) and angiographically significant superficial femoral and popliteal PAD at 34 centers in the United States, Europe, and New Zealand. More than three-quarters of the study population had Rutherford category 3 severe claudication. The average lesion length was 78.1 mm, and nearly half of patients in the study had moderate-to-severe calcification. Atherectomy was allowed and was used in 12% of the Chocolate Touch group and 11% of the Lutonix group. None of the patients in either group require clinically-driven bailout stenting after DCB. Technical and device success between the two groups were similar.

At 12-month follow-up, 78.8% of Chocolate Touch patients and 67.7% of Lutonix patients achieved the primary endpoint of patency (P < 0.0001 for noninferiority). Primary patency as assessed by duplex ultrasound was 77.1% with Chocolate Touch versus 66.2% with Lutonix (P = 0.059), and stent-free patency was 76.0% versus 65.8%; (P = 0.0934). The rates of freedom from clinically driven TLR were similar between groups (93.7% Chocolate Touch versus 88.6% Lutonix DCB).

We need to understand what was driving the difference, so we will know how to iterate on that going forward. Geoffrey Barnes

Additionally, an analysis of time free from loss of patency at 12 months also favored the Chocolate Touch group, at 83.3% versus 73.0% of the Lutonix group (P = 0.04).

The primary safety endpoint of freedom at 12 months from major adverse events (a composite of target limb-related death, amputation, or reintervention) was not different between the Chocolate Touch and Lutonix groups (88.9% vs 84.6%; P = 0.0001 for noninferiority). There were no significant differences between groups in terms of dissection rates or flow-limiting dissections.

At 12 months, there was one death in the Chocolate Touch group and two in the Lutonix group. The investigators also assessed long-term mortality to address ongoing concerns raised by a 2018 meta-analysis of RCTs led by Konstantinos Katsanos, MD, PhD (Patras University Hospital, Rion, Greece), that found a late mortality increase beginning at 2 to 3 years postprocedure in patients treated with paclitaxel-based DES or DCB compared with a plain balloon or plain stent. The Chocolate Touch study was one of several trials that were stopped in 2019 as investigators, industry, and the US Food and Drug Administration grappled with paclitaxel-based device use.

There were no differences in rates of death with Chocolate Touch versus Lutonix at 2 years and again at 3 years, although only a few dozen patients thus far have reached 3-year follow-up. A post hoc Bayesian predictive analysis suggested a 86.3% probability that the 3-year mortality rate in the Chocolate group will be lower than a prespecified performance goal derived from mortality rates of paclitaxel-treated patients in a patient-level meta-analysis.

To TCTMD, co-author Alexandra Lansky, MD (Yale University School of Medicine, New Haven, CT), said in a prior study that tested an uncoated version of Chocolate Touch there were fewer acute dissections compared with standard DCB, suggesting it does reduce the occurrence of dissections, which are a limitation of the other commercially available DCBs for PAD.

She added that it is likely a combination of the dose, the polymer, and the pillow-groove design that contributes to the success of Chocolate Touch.

“I can tell you that in an animal studies, what we're seeing in the first 15 days is higher levels of drug in the vessel wall compared to the comparator that we used, the Lutonix balloon,” she said. Lansky added that the next step is to submit the data to the FDA and get it approved and on the market.