Author + information
- Piotr P. Buszman, MD, PhD,
- Przemysław Nowakowski, MD, PhD,
- Krzysztof Milewski, MD, PhD,
- Bartłomiej Orlik, MD, PhD,
- Aleksander Żurakowski, MD, PhD,
- Tomasz Ludyga, MD, PhD,
- Filip Polczyk, MPH,
- Marcin Dębiński, MD, PhD,
- Michał Jelonek, MD, PhD,
- Mateusz Kachel,
- Mariusz Gąsior, MD, PhD,
- Juan F. Granada, MD,
- Radosław S. Kiesz, MD, PhD and
- Paweł E. Buszman, MD, PhD∗ ()
- ↵∗Center for Cardiovascular Research and Development, American Heart of Poland Inc., 41 Czajek Street, Katowice 40-761, Poland
Paclitaxel-coated balloons (PCBs) have reduced restenosis and repeat revascularizations when compared with plain balloon angioplasty (PBA) alone after revascularization of superficial femoral arteries. On the other hand, concerns have been raised due to paclitaxel particle shedding during intervention and distal embolization. Second-generation PCBs consist of more homogenous and microparticle paclitaxel coatings that have shown improved vessel healing with sustained efficacy in an animal model when compared with first-generation technology (1). Nevertheless, clinical data on their safety and efficacy remain limited. Therefore, we evaluated a novel, microcrystalline PCB (mcPCB) (Balton, Warsaw, Poland) with a Poligrade polymer technology in the setting of a clinical trial.
The BIOPAC (First-in-Man Evaluation of a Novel, Microcrystalline Paclitaxel Coated Balloon for Treatment of Femoropopliteal Artery Disease) trial is a multicenter prospective, controlled, single-blind clinical randomized trial comparing late lumen loss (LLL) in femoropopliteal occlusive lesions treated with the mcPCB versus an uncoated control (PBA). Eligible participants were >18 years of age with claudication in Rutherford category 2 to 4. Lesion criteria for enrolment included occlusive or total single de novo or non-stent restenotic lesions in the superficial femoral arteries (>50% diameter stenosis; length >4 cm and <15 cm). Lesions were eligible for the study providing successful crossing with a guidewire. Bailout stenting was at the operator’s discretion in case of severe dissection and/or flow impairment. We excluded patients with acute coronary syndromes, reduced ejection fraction heart failure, below-the-knee lesions, chronic kidney disease, femoropopliteal grafts, history of stroke within 6 months, and life expectancy <2 years.
The study complied with the declaration of Helsinki, and the protocol was approved by the institutional and local ethics committees. All patients provided written, informed consent for participation in this trial. The trial has been registered at ClinicalTrials.gov (NCT02145065).
LLL assessed by the independent core lab at 6 months by angiography was the primary outcome measure. To prove the study hypothesis, 66 patients (33 in each group) were required to have a 80% chance of determining, as significant at the 5% level, the difference in the LLL from 0.3 mm in the study group to 1 mm in the experimental group and 1-mm SD.
In total, 66 patients were included, 33 randomized to the mcPCB group and 33 to PBA (uncoated control) in which 34 and 35 lesions, respectively, were treated consecutively via a femoral approach and standard techniques. At 6 months, 30 patients in each group underwent angiography. At 12 months, follow-up was completed for 32 patients in the mcPCB group and 29 in PBA. This included 29 and 27 ambulatory visits, respectively.
Patients’ baseline characteristics and outcomes are presented in Table 1. The primary endpoint, LLL, was reduced by 63% when compared with PBA, thus meeting criteria for superiority (p < 0.01). The binary restenosis was more than 2-fold lower in the mcPCB group.
In this trial, the novel mcPCB has proved superior in LLL reduction when compared with PBA in patients after revascularization of occlusive, femoropopliteal disease. Consequently, binary restenosis in angiography was significantly lower, and primary patency rates at 1 year were higher in the mcPCB group. Although underpowered, the composite endpoint of serious adverse events at 12 months was significantly lower by nearly 3-fold when compared with the control group, driven by the significant, more than 2-fold reduction in repeated revascularization rates, which were sustained up to 1-year follow-up. There was no thrombosis or amputations of any of the treated limbs. All deaths in the PBA arm were cardiac.
The novelty of the tested PCB is 2-factorial. First, the coating consists of microcrystalline paclitaxel particles, which have shown the reduction of particle release (data on file at Balton). Second, the novel, proprietary Poligrade polymer-based technology has been used as a carrier. In the preclinical setting, the tested mcPCB has shown 50% reduction of neontimal hyperplasia when compared with PBA, whereas healing was complete (2). The first-in-man clinical trial results resemble the preclinical outcomes.
The LLL reduction achieved by the mcPCB in the current study is larger when compared with previously reported trials with first-generation PCB and with similar lesion characteristics. Thus, the smaller population was sufficient to prove the study hypothesis. The reduced rates of repeat revascularizations are similar to previous reports in which first-generation 3 μg/mm2 paclitaxel concentration was used, and better when compared with second-generation, 2 μg/mm2 PCBs (3,4).
In summary, this novel technology has proven superiority in LLL reduction; however, it deserves further investigation on larger populations to prove reduction of clinical outcomes. A trial in different anatomies and with first-generation technologies is also anticipated.
Please note: This study has been funded by unrestricted research grant from by Balton Company, Warsaw, Poland. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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