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.
OBJECTIVE
This study sought to evaluate the safety and efficacy of the Lutonix drug-coated balloon (DCB) coated with 2 μg/mm(2)paclitaxel and a polysorbate/sorbitol carrier for treatment of femoropopliteal lesions.


BACKGROUND
Percutaneous treatment of peripheral vascular disease is associated with a high recurrence. Paclitaxel-coated balloons at 3 μg/mm(2) formulated differently have shown promising results with reduced restenosis. Methods Subjects at 9 centers with Rutherford class 2 to 5 femoropopliteal lesions were randomized between June 2009 and December 2009 to treatment with Lutonix DCB (n = 49) versus uncoated balloons (control group [n = 52]), stratified by whether balloon-only treatment (n = 75) or stenting (n = 26) was intended. The primary endpoint was angiographic late lumen loss at 6 months. Secondary outcomes included adjudicated major adverse events (death, amputation, target lesion thrombosis, reintervention), functional outcomes, and pharmacokinetics.


RESULTS
Demographic, peripheral vascular disease, and lesion characteristics were matched, with mean lesion length of 8.1 3.8 cm and 42% total occlusions. At 6 months, late lumen loss was 58% lower for the Lutonix DCB group (0.46 1.13 mm) than for the control group (1.09 1.07 mm; p = 0.016). Composite 24-month major adverse events were 39% for the DCB group, including 15 target lesion revascularizations, 1 amputation, and 4 deaths versus 46% for uncoated balloon group, with 20 target lesion revascularizations, 1 thrombosis, and 5 deaths. Pharmacokinetics showed biexponential decay with peak concentration (Cmax) of 59 ng/ml and total observed exposure (AUC(all)) of 73 ng h/ml. For successful DCB deployment excluding 8 malfunctions, 6-month late lumen loss was 0.39 mm and the 24-month target lesion revascularization rate was 24%.


CONCLUSIONS
Treatment of femoropopliteal lesions with the low-dose Lutonix DCB reduced late lumen loss with safety comparable to that of control angioplasty. (LEVANT I, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis; NCT00930813)
Center of Vascular Medicine, Heart Center Leipzig/Park Hospital, Leipzig, Germany. Electronic address: dierk.scheinert@gmx.de.
Dierk
D
Scheinert
Center for Diagnostic Radiology and Minimally Invasive Therapy, Jewish Hospital, Berlin, Germany.
Stephan
S
Duda
Department of Interventional Angiology, Herz-Zentrum, Bad Krozingen, Germany.
Thomas
T
Zeller
Cardiovascular Center, Hamburg University Cardiovascular Center, Hamburg, Germany.
Hans
H
Krankenberg
Clinic for Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany.
Jens
J
Ricke
Flanders Medical Research Program, Department of Vascular Surgery, St. Blasius Hospital, Dendermonde, Belgium.
Marc
M
Bosiers
Department of Diagnostic and Interventional Radiology, RoMed Academic Hospital of Rosenheim, Rosenheim, Germany.
Gunnar
G
Tepe
Lutonix, Inc., New Hope, Minnesota.
Scott
S
Naisbitt
Department of Medicine-Cardiology, Massachusetts General Hospital, Cambridge, Massachusetts.
Kenneth
K
Rosenfield
D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020099:Coated Materials, Biocompatible; D003251:Constriction, Pathologic; D004337:Drug Carriers; D004867:Equipment Design; D005060:Europe; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D006801:Humans; D023821:Limb Salvage; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011136:Polysorbates / Q000737:chemistry; D011150:Popliteal Artery / Q000000981:diagnostic imaging; D011859:Radiography; D055502:Secondary Prevention; D013012:Sorbitol / Q000737:chemistry; D013997:Time Factors; D016896:Treatment Outcome; D062666:Vascular Access Devices
D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D011136:Polysorbates; D013012:Sorbitol; D017239:Paclitaxel
DCB; ITT; LLL; PK; TLR; angioplasty; drug-coated balloon; drug-coated balloon(s); drug-eluting balloon; intention to treat; late lumen loss; paclitaxel; peripheral vascular disease; pharmacokinetics; restenosis; target lesion revascularization(s)