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.

Abstract

Objectives: 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)

Keywords: 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).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amputation, Surgical
  • Angioplasty, Balloon / adverse effects
  • Angioplasty, Balloon / instrumentation*
  • Angioplasty, Balloon / mortality
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / pharmacokinetics
  • Coated Materials, Biocompatible*
  • Constriction, Pathologic
  • Drug Carriers
  • Equipment Design
  • Europe
  • Female
  • Femoral Artery* / diagnostic imaging
  • Humans
  • Limb Salvage
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / mortality
  • Peripheral Arterial Disease / therapy*
  • Polysorbates / chemistry
  • Popliteal Artery* / diagnostic imaging
  • Radiography
  • Secondary Prevention
  • Sorbitol / chemistry
  • Time Factors
  • Treatment Outcome
  • Vascular Access Devices*

Substances

  • Cardiovascular Agents
  • Coated Materials, Biocompatible
  • Drug Carriers
  • Polysorbates
  • Sorbitol
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00930813