Download this article's Factoid (PDF & PPT for Gold Subscribers)

A novel drug-coated balloon (DCB) shows encouraging safety and clinical efficacy out to 2 years in patients with superficial femoral and/or popliteal lesions, according to findings from a small, preliminary study presented May 22, 2014, at EuroPCR in Paris, France.

Stephan Duda, MD, of Jewish Hospital Berlin (Berlin, Germany), updated 12-month results from the ILLUMENATE First-in-Human Study reported at EuroPCR the previous year.

For the prospective, single-arm study, 58 superficial femoral and/or popliteal lesions in 50 patients enrolled at 3 German centers were first predilated with an uncoated balloon. This was followed by treatment with the Stellarex paclitaxel-coated balloon (Covidien; Mansfield, MA). A small percentage of patients with residual stenosis >50% or a significant dissection also received postdilatation (12.1%) or BMS (3.4%).

Lesions measured 72.1 ± 46.7 mm, and almost two-thirds were calcified (62.1%). Most patients were Rutherford class 2 (16%) or 3 (82%); none was class 5.

The study also enrolled a cohort of 30 patients who did not undergo predilatation; those results are being analyzed separately and are not yet available.

According to Covidien, the Stellarex DCB has a durable, uniform coating designed to help prevent drug loss during balloon transit and facilitate controlled, efficient drug delivery to the treatment site.

Safety, Angiographic Metrics Favorable

Device success was 96.6%, with only a 5.6% incidence of geographic miss. Percent stenosis declined from 75.1 ± 17.0% at baseline to 19.1 ± 9.7% post procedure, while the minimum lumen diameter increased from 1.3 ± 1.0 mm to 4.3 ± 0.7 mm (both P < .001).

At 6 months, late lumen loss at 0.54 mm met the prespecified endpoint of being 13.7% below an objective performance criterion. Meanwhile, the rate of major adverse events (CV death, index limb amputation, and clinically driven TLR) was low at 4% and due entirely to TLR.

In follow-up of 43 patients, Dr. Duda reported, Kaplan-Meier curves estimated high long-term patency and low TLR rates (table 1). There were no CV deaths or amputations.

Table 1. Kaplan-Meier Estimates of Long-Term Outcomes

^a 86.1% when bailout stenting was considered patency failure.

The outcomes augur well for the potential cost-effectiveness of the Stellarex DCB in this patient population, Dr. Duda said, adding that several studies including a randomized controlled trial in Europe, a pivotal US study, and a global registry are currently under way to attempt to validate the first-in-human results.

The Coating Is Key

According to Juan F. Granada, MD, of the CRF Skirball Research Center (Orangeburg, NY), the Stellarex drug coating is less crystalline than earlier technologies and carries a lower paclitaxel concentration of about 2 μg/mm².

“In theory, when you decrease the surface concentration of the drug and have the right coating formulation, you have the potential to minimize any possible side effects caused by the drug while still maintaining therapeutic tissue levels,” he explained to TCTMD in a telephone interview.

In particular, the lower drug concentration decreases the risk of distal embolization, and that may be important in light of recent findings from the IN.PACT DEEP trial, which reported a trend toward increased amputations in below-the-knee patients with the In.Pact Amphirion DCB (Medtronic; Minneapolis, MN) carrying 3 μg/mm² of paclitaxel, he added.

In an email with TCTMD, Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), largely discounted concerns about embolization, but he agreed that “the coating composition and coating processes are the most important factors determining efficacy and tolerance.” In addition, he observed, the optimal dose of paclitaxel on the balloon remains unknown, so exploration of different formulations is warranted.

“So far, the best-in-class data from randomized trials have been reported for the paclitaxel urea coating with 3 μg/mm²,” he noted. “In the PACIFIER trial [testing the In.Pact Pacific DCB (Medtronic)], late lumen loss at 6 months was -0.05 mm vs 0.54 mm in the ILLUMENATE FIH data.”

Overall, the lesion characteristics in the current study—relatively short, with low prevalence of severe calcification and total occlusion—are comparable to trials testing other new-generation DCBs, and so is the 6-month late lumen loss, Dr. Granada observed.

Does This Device Hold a Possible Edge?

But intriguingly in this FIH trial the Stellarex DCB showed a markedly higher rate of 24-month primary patency than did Lutonix (BARD; Murray Hill, NJ) in the LEVANT I trial despite a similar 2 μg paclitaxel concentration, he said, adding that if larger randomized trials uphold this advantage and unmask other differences, they may become important considerations in clinicians’ choice of technology.

“It’s all about pharmacokinetics, and the coating characteristics determine the long-term pharmacokinetics,” Dr. Granada concluded. “Having the same surface concentration [of paclitaxel] doesn’t necessarily mean that the pharmacokinetic behavior is going to be similar. That has to do with crystallinity, solubility, and tissue residency.

“The new-generation technologies have moved into large randomized trials in the United States [aiming for US Food and Drug Administration] approval,” he continued. “The Stellarex DCB is the third technology that is showing viability in this field, with very durable effects at 2 years in a highly selected group of patients.”
 

Related Stories:

• Paclitaxel Delivery Key to PAD Intervention
• Pair of Studies Support Paclitaxel-Eluting Devices for Treating Femoropopliteal Disease
• Drug-Eluting Balloon Provides Strong Primary Patency in SFA at 1 Year