First-in-man Evaluation of a Novel, Microcrystalline Paclitaxel Coated Balloon for Treatment of Femoropopliteal Artery Disease (PAX-r) (PAX)

Prospective, Pivotal, First - in Man Clinical Trial of the Safety and Efficacy of a Novel Microcrystalline Paclitaxel Coated Balloon for Treatment of Femoropopliteal Artery Disease

The purpose of this pivotal, first in man study will be to evaluate safety and efficacy of the novel, microcrystalline paclitaxel coated balloon (mcPCB, PAK, Balton) in the treatment of femoropopliteal artery disease.

Study Overview

• Status: Completed
• Conditions: Peripheral Artery Disease; Femoropopliteal Artery Disease
• Intervention / Treatment: Device: Plain balloon angioplasty, uncoated balloon (Neptun, Balton, Poland); Drug: Local drug delivery via microcrystalline paclitaxel balloon coating (PAK,Balton, Poland)

Detailed Description

Although clinically effective, the manufacturing process of first generation PCB coatings contributed to inconsistent drug concentrations, particulate formations on the balloon surface and their shedding during the interventional procedures. As a consequence developments of new PCB coatings have been proposed to address consistency, uniformity, small particle drug coverage, which may potentially contribute to improved vessel healing profile and improved clinical outcomes. Nevertheless, data on the safety and efficacy of this novel coating developments in the clinical setting remain limited. Previously in the experimental model, the investigators reported that delivery of paclitaxel via a novel mcPCB resulted in low long-term tissue retention of paclitaxel, however displayed reduced neointimal proliferation and favorable healing profile. Therefore in current clinical trial the investigators will address the feasibility and safety of the mcPCB (PAK, Balton) in the treatment of femoropopliteal restenotic disease in a prospective, randomized manner when compared to plain balloon angioplasty (PBA). The efficacy analysis will be observational and evaluated post-hoc, with no prespecified criteria.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Chrzanów, Poland, 32-500
    • Lesser-Poland Cardiovascular Center of American Heart of Poland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 y.o.
• Claudication in Rutherford Class 1-5,
• Lesion in the femoropopliteal artery defined as >50% and < 99% diameter stenosis with length of up to 10 cm in vessel diameter of 3-7 mm
• Chronic total occlusions of length less than 100 mm
• Ability to cross the lesions with a guidewire.

Exclusion Criteria:

• Critical acute or chronic limb ischemia
• Acute coronary syndrome
• Chronic kidney disease stage III-V
• Restenotic lesion
• Femoropopliteal graft
• Known allergy to clopidogrel or aspirin
• History of stroke within past 6 months
• Age > 80 y.o.
• Life expectancy < 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Plain Balloon Angioplasty	Device: Plain balloon angioplasty, uncoated balloon (Neptun, Balton, Poland)
Experimental: microcrystalline Paclitaxel Coated Balloon (PAK); plain balloon angioplasty followed by mcPCB dilation	Drug: Local drug delivery via microcrystalline paclitaxel balloon coating (PAK,Balton, Poland)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Angiographic late lumen loss	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Device related adverse events		30 days, 6 months
Critical limb ischemia		30 days, 6 months
Device Success	Successful delivery and deployment of the first inserted study device (in overlapping setting a successful delivery and deployment of the first and second study device) at the intended target lesion and successful withdrawal of the study device with attainment of final residual stenosis of less than 30% of the target lesion by quantitative vessel angiography (QVA).	at procedure
Target Lesion Revascularization		6, 12, 24 months
Target vessel revascularization		6, 12, 24 months
Primary patency of treated segment		6, 12, 24 months
Treated limb amputation		30 days, 6 months

Other Outcome Measures

Outcome Measure	Time Frame
Change in ankle-brachial index	pre-procedure, 3,6 and 12 months
Change in Walking Impairment Questionnaire (WIQ)	pre procedure, 3, 6 and 12 months
Flow velocity in doppler ultrasonography	3, 6 and 12 months

Collaborators and Investigators

• Sponsor: Balton Sp.zo.o.
• Collaborators: American Heart of Poland
• Investigators: Principal Investigator: Przemysław Nowakowski, M.D., PhD, American Heart of Poland, Katowice, Poland; Principal Investigator: Piotr P Buszman, M.D., PhD, American Heart of Poland, Katowice, Poland

Publications and helpful links

General Publications

• Tepe G, Zeller T, Albrecht T, Heller S, Schwarzwalder U, Beregi JP, Claussen CD, Oldenburg A, Scheller B, Speck U. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008 Feb 14;358(7):689-99. doi: 10.1056/NEJMoa0706356.
• Werk M, Langner S, Reinkensmeier B, Boettcher HF, Tepe G, Dietz U, Hosten N, Hamm B, Speck U, Ricke J. Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Circulation. 2008 Sep 23;118(13):1358-65. doi: 10.1161/CIRCULATIONAHA.107.735985. Epub 2008 Sep 8. Erratum In: Circulation. 2008 Oct 14;118(16):e670.
• Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, Bohm M, Speck U. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med. 2006 Nov 16;355(20):2113-24. doi: 10.1056/NEJMoa061254. Epub 2006 Nov 13.
• Scheinert D, Duda S, Zeller T, Krankenberg H, Ricke J, Bosiers M, Tepe G, Naisbitt S, Rosenfield K. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon angioplasty. JACC Cardiovasc Interv. 2014 Jan;7(1):10-9. doi: 10.1016/j.jcin.2013.05.022.
• Buszman PP, Milewski K, Zurakowski A, Pajak J, Jelonek M, Gasior P, Peppas A, Tellez A, Granada JF, Buszman PE. Experimental evaluation of pharmacokinetic profile and biological effect of a novel paclitaxel microcrystalline balloon coating in the iliofemoral territory of swine. Catheter Cardiovasc Interv. 2014 Feb;83(2):325-33. doi: 10.1002/ccd.24982. Epub 2013 Oct 23.
• Nowakowski P, Uchto W, Hrycek E, Kachel M, Ludyga T, Polczyk F, Zurakowski A, Kazmierczak P, Granada JF, Nowakowska I, Kiesz RS, Milewski KP, Buszman PE, Buszman PP. Microcrystalline paclitaxel-coated balloon for revascularization of femoropopliteal artery disease: Three-year outcomes of the randomized BIOPAC trial. Vasc Med. 2021 Aug;26(4):401-408. doi: 10.1177/1358863X20988360. Epub 2021 Mar 9.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: May 20, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (Estimate): May 22, 2014

Study Record Updates

• Last Update Posted (Actual): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: restenosis; paclitaxel coated balloon; Femoropopliteal artery disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: PAX-0314