European All-comers' Multicentric Prospective REGISTRY on LUMINOR© Drug Eluting Balloon in the Superficial Femoral Artery and Popliteal Artery With 5 Years Follow-up.

Study Overview
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Brief Summary
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The objective of this all-comers registry is to explore the safety, efficacy, and cost-efficiency of the LUMINOR© DEB in de-novo and restenotic-FP lesions. For de-novo and restenotic lesions, especially for calcified and/or long lesions/occlusions, the use of debulking devices to improve recalibration and drug penetration will be evaluated in a specific sub-group.

Official Title
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European All-comers' Multicentric Prospective REGISTRY on LUMINOR© Drug Eluting Balloon in the Superficial Femoral Artery and Popliteal Artery With 5 Years Follow-up.

Conditions
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Angioplasty, Peripheral Arterial Disease, Drug-eluting Balloon, Femoral Artery, Paclitaxel

Intervention / Treatment
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* Device: LUMINOR© Paclitaxel eluting balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Rutherford Clinical Category 2-5 The subject is legally competent, has been informed of the nature, the scope, and the relevance of the study, voluntarily agrees to participation, is willing to provide 5-year informed consent and has duly signed the informed consent form (ICF) Significant (≥ 70%) stenosis or occlusion of a native femoropopliteal artery TASC II Class A to D Lesions de novo lesion(s), non-stented or stented restenotic lesion(s) Proximal margin of target lesion(s) starts at the ostium of the superficial femoral artery, just below the common femoral bifurcation Distal margin of target lesion(s) terminates at bifurcation of popliteal artery AND ≥1 cm above the origin of the TP trunk (P3) A patent inflow artery free from significant lesion (≥ 50% stenosis) as confirmed by angiography (treatment of target lesion acceptable after successful treatment of iliac or common femoral inflow artery lesions); Successful inflow artery treatment is defined as attainment of residual diameter stenosis ≤ 30% without death or major vascular complication Successful wire crossing and pre-dilatation (1min min, with under sizing of 1mm compared to ref diameter) of the target lesion; Use of crossing devices allowed if necessary. Use of laser or atherectomy is allowed if necessary, during the index procedure. Bailout stenting is allowed if necessary, after DEB use At least one patent native outflow artery to the ankle, free from significant (≥ 50%) stenosis as confirmed by angiography (treatment of outflow disease is NOT permitted during the index procedure) Exclusion Criteria: Women who are pregnant, lactating, or planning on becoming pregnant or men intending to father children Patient is contraindicated to use Luminor Drug Eluting Balloon per the current Instructions For Use (IFU) Life expectancy of < 1year Patient is currently participating in an investigational drug or other device study or previously enrolled in this study Inability to take required study medications or allergy to contrast that cannot be adequately managed with pre- and post-procedure medication Sudden symptom onset, acute vessel occlusion, or acute or sub-acute angiographically visible thrombus in target vessel

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LUMINOR© drug eluting balloon<br> | Device: LUMINOR© Paclitaxel eluting balloon<br>* Patients will be treated with the Luminor paclitaxel eluting balloon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint Efficacy measured by presence of primary patency of the target lesion based on ultrasound images | Primary Patency is defined as Freedom from Clinically-Driven Target Lesion Revascularization and from Binary Restenosis. | 12 Months | 
| Overall Medical Safety | Combination assessment of freedom from all-cause peri-procedural (≤30 day) death and freedom at 3 years from the following: index limb amputation (above or below the ankle), and all-cause mortality (with a detailed analysis of cardiovascular (CV) and non-CV deaths). Success is defined as freedom from all specified events; failure is defined as one or more specified events occurrences. | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint Medical Safety: Major vascular complications | Major vascular complications will be counted: Haematoma at access site >5 cm False aneurysm AV fistula Retroperitoneal bleeding Peripheral ischemia/nerve injury Any transfusion required will be reported as a vascular complication unless clinical indication clearly other than catheterization complication Vascular surgical repair | ≤30 days after index procedure | 
| Secondary Endpoint Medical Safety: Composite Safety | Combination assessment of freedom from all-cause death and freedom from the following: index limb amputation (above or below the ankle = major or minor amputation) and index limb re-intervention. Success is freedom from all specified events; failure is occurrence of one or more specified events. | 1, 6, 12, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Medical Safety: All-cause death | Death by any cause will be counted and stratified between CV and non-CV deaths. Cause of death will be analyzed to search for any specific increase of a death's subtype. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Medical Safety: Major amputation at target limb | Amputations above the ankle of the target leg will be counted. Optional histologic examination of fixed muscle segments in 10% neutral-buffered formalin could be performed in the Inserm unit 1034, Pessac, France to search for paclitaxel microparticle deposits, fibrinoid necrosis artery wall injury, inflammation, thrombus, hemorrhage, and fibrosis. Adjacent nonfixed samples of similar distal tissues, flash-frozen in liquid nitrogen, and retained at -80°C will be used for bioanalysis of paclitaxel levels by modified liquid chromatography/tandem mass spectroscopy. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Medical Safety: Minor amputation at target limb | Amputations below the ankle of the target leg will be counted. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Medical Safety: Target Vessel Revascularization (TVR) | Repeat intervention at the target vessel will be counted. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Medical Safety: Target Limb Reintervention | Repeat intervention at the target leg will be counted. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Acute Device Success | Device success is defined as, a per device basis, the achievement of successful delivery and deployment of the study device(s) as intended at the intended target lesion, without balloon rupture or inflation/deflation abnormalities and a successful withdrawal of the study system. If a device is inserted into the subject but not used due to user error (e.g. inappropriate balloon length or transit time too long), this device will not be included in the device success assessment. | During index procedure | 
| Secondary Endpoint Efficacy: Technical Success | Technical Success of the balloon procedure is defined as successful access and deployment of the device and visual estimate of ≤ 30% diameter residual stenosis during the index procedure. | During index procedure | 
| Secondary Endpoint Efficacy: Procedural Success | Attainment of ≤ 30% residual stenosis in the treatment area without major adverse events (defined as occurrence of death, major amputation of the target limb, target vessel or distal revascularization) during the index procedure and through the hospital stay. | Up to 30 days | 
| Secondary Endpoint Efficacy: Primary Patency | Primary Patency is defined as Freedom from Clinically-Driven Target Lesion Revascularization and from Binary Restenosis. Binary restenosis is adjudicated by the validated center based on threshold Doppler PSVR ≥ 2.5 (together with waveform analysis & color mosaic appearance) or based on angiographic ≥ 50% diameter stenosis (if angiography is performed although not required per protocol). | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Secondary Patency | Secondary Patency of the target lesion is defined as the absence of binary restenosis as adjudicated by the validated center, independent of whether or not patency is re-established via an endovascular procedure. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Clinically-driven Target Lesion Revascularization (TLR) | Revascularization of the target lesion with evidence of diameter stenosis >50% determined by duplex ultrasound or angiography and new distal ischemic signs (worsening ABI or worsening Rutherford Category associated with the target limb or due to clinical symptoms). | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Target Lesion Revascularization (TLR) | A repeat revascularization procedure (percutaneous or surgical) of the original target lesion site. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Change of Rutherford classification from baseline | Patients are enrolled with a Rutherford grade of 2-5 for their target leg. The Rutherford scale is an indicator for the severity of Peripheral Vascular Disease: 0 = no symptoms, 6 = functional foot is no longer salvageable (leading to foot amputation). | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Change of resting Ankle Brachial Index (ABI) from baseline | The ABI values will be recorded and compared to the baseline values. The ABI is the ratio of the blood pressure at the ankle to the blood pressure in the upper arm. A ratio of 0.9-1.3 is in the normal range. Lower ratios indicate bad blood perfusion of the leg. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Change in Walking Impairment Questionnaire from baseline | The Walking Impairment Questionnaire values will be recorded and compared to the baseline values. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Efficacy: Change in quality of life from baseline, as measured by EQ-5D | The EQ-5D Questionnaire values will be recorded and compared to the baseline values. | 1, 6, 12, 24, 36, 48, 60 months after index procedure | 
| Secondary Endpoint Cost-Effectiveness (optional): factoring procedure and hospital admission costs |  | 1, 6, 12, 24, 36, 48, 60 months after index procedure |