Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial.

BACKGROUND: Drug-coated balloons (DCBs) have shown promise in improving the outcomes for patients with peripheral artery disease. We compared a paclitaxel-coated balloon with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic superficial femoral and popliteal artery disease. METHODS AND RESULTS: The IN.PACT SFA Trial is a prospective, multicenter, single-blinded, randomized trial in which 331 patients with intermittent claudication or ischemic rest pain attributable to superficial femoral and popliteal peripheral artery disease were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The primary efficacy end point was primary patency, defined as freedom from restenosis or clinically driven target lesion revascularization at 12 months. Baseline characteristics were similar between the 2 groups. Mean lesion length and the percentage of total occlusions for the DCB and PTA arms were 8.94 ± 4.89 and 8.81 ± 5.12 cm (P=0.82) and 25.8% and 19.5% (P=0.22), respectively. DCB resulted in higher primary patency versus PTA (82.2% versus 52.4%; P<0.001). The rate of clinically driven target lesion revascularization was 2.4% in the DCB arm in comparison with 20.6% in the PTA arm (P<0.001). There was a low rate of vessel thrombosis in both arms (1.4% after DCB and 3.7% after PTA [P=0.10]). There were no device- or procedure-related deaths and no major amputations. CONCLUSIONS: In this prospective, multicenter, randomized trial, DCB was superior to PTA and had a favorable safety profile for the treatment of patients with symptomatic femoropopliteal peripheral artery disease. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT01175850 and NCT01566461.

Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial.

BACKGROUND: Drug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation. OBJECTIVES: The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI). METHODS: Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR. RESULTS: Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080). CONCLUSIONS: In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733).

IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial.

BACKGROUND: The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate "patient-centric" outcomes of functional limb preservation, mobility and quality of life (QoL). METHODS/DESIGN: IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. DISCUSSION: This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are discussed. IN.PACT DEEP is a milestone, prospective, randomized, robust, independent core lab-adjudicated CLI trial that will evaluate the role of a new infrapopliteal revascularization technology, the IA-DEB, compared to PTA. It will assess the overall impact on infrapopliteal artery patency, limb salvage, wound healing, pain control, QoL, and patient mobility. The 1-year results of the adjudicated co-primary and secondary endpoints will be available in 2014. TRIAL REGISTRATION: NCT00941733.