Vascular Effects Through Sirolimus vs. Paclitaxel DCB Implantation

Study Overview
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Brief Summary
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Endovascular treatment of symptomatic atherosclerotic peripheral artery disease (PAD) is recommended as the primary revascularization strategy. Percutaneous transluminal angioplasty (PTA) of the superficial femoral artery has a high initial success rate, but restenosis and dissections frequently occur.The influence of the novel devices with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance can be measured by FMD (flow-mediated dilation), arterial stiffness indices and vascular strain analysis. The aim of this ITT is to determine the potential improvement and impact of the SELUTION SLR in the infrainguinal arteries on local vascular function.

Detailed Description
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Endovascular treatment of symptomatic atherosclerotic peripheral artery disease (PAD) is recommended as the primary revascularization strategy. Percutaneous transluminal angioplasty (PTA) of the superficial femoral artery has a high initial success rate, but restenosis and dissections frequently occur. While restoration of tissue perfusion is achieved, these interventional strategies affect vascular function, perpetuating dysfunctional vascular homeostasis. Vascular and endothelial dysfunction per se is the pathophysiologic principle involved in the initiation and progression of atherosclerosis and has been correlated to higher incidences of cardiac events such as myocardial infarction or the need for interventions. PTA and DCB treatment alter the endothelial homeostasis but the impact and detailed mechanisms are incompletely understood. The influence of the novel devices with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance can be measured by FMD (flow-mediated dilation), arterial stiffness indices and vascular strain analysis. The aim of this ITT is to determine the potential improvement and impact of the SELUTION SLR in the infrainguinal arteries on local vascular function. Device to be used are SELUTION SLR™ (Sustained Limus Release) drug eluting balloon (n = 35) vs. Active comparator, Paclitaxel eluting balloon (Medtronic InPact, n = 35) The analysis of the primary end point will be performed on an intention-to-treat basis. Subgroup analyses will be performed according to PAD classification etiology and based on stent length.

Official Title
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Scientific Proposal to Substantiate Vascular Effects Through Sirolimus vs. Paclitaxel DCB Implantation

Conditions
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Peripheral Arterial Disease, Flow-mediated Dilation, Drug Eluting Balloon, Infrainguinal Peripheral Arterial Disease

Intervention / Treatment
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* Device: SELUTION SLR DCB
* Device: Paclitaxel DCB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Peripheral artery disease Target lesions 3 cm distal to the CFA-bifurcation including SFA and PA lesions Clinical diagnosis of chronic, symptomatic lower limb ischemia as defined by Rutherford 2, 3, 4 and 5 Planed peripheral intervention TASC A-D Subject must be between 18 and 85 years old Female of childbearing potential must have a negative pregnancy test within 10 days prior to index procedure and utilize reliable birth control until completion of the 12-month angiographic evaluation Vessel diameter ≥4.0 mm and ≤7.0 mm Willing to comply with the specified follow-up evaluation Written informed consent prior to any study procedures Pretreatment with an adequately sized balloon Exclusion Criteria: Bifurcational lesions of the CFA and lesions including the first 3 cm of the SFA, due to technical aspects of FMD measurement Instent-Restenosis Thrombolysis within 72 hours prior to the index procedure Aneurysm formations in the femoral artery or popliteal artery Concomitant hepatic insufficiency, deep venous thrombus, coagulation disorder or receiving immunosuppressant therapy Unstable angina pectoris at the time of the enrollment Recent myocardial infarction or stroke < 30 days prior to the index procedure Life expectancy less than 12 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SELUTION SLR DCB<br>Sustained Limus Release drug eluting balloon | Device: SELUTION SLR DCB<br>* Sirolimus DCB<br>|
| Active Comparator: Paclitaxel eluting balloon<br>Conventional: Medtronic INpact | Device: Paclitaxel DCB<br>* Paclitaxel DCB<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of flow-mediated vasodilation (FMD) of the nonstenotic segment of the proximal SFA after procedure | FMD represents the percent diameter gain as calculated based on preischemia and postischemia diameter measurements of the femoral artery | 1 month | 
| Change of flow-mediated vasodilation (FMD) of the nonstenotic segment of the proximal SFA after procedure | FMD represents the percent diameter gain as calculated based on preischemia and postischemia diameter measurements of the femoral artery | 6 months | 
| Change of flow-mediated vasodilation (FMD) of the nonstenotic segment of the proximal SFA after procedure | FMD represents the percent diameter gain as calculated based on preischemia and postischemia diameter measurements of the femoral artery | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pulse wave velocity (PWV) | Changes in cardiovascular function measured by pulse wave velocity in m/s | Baseline, followed at 1, 6 and 12 months | 
| Changes in augmentation index | Changes in cardiovascular function measured by augmentation index in % | Baseline, followed at 1, 6 and 12 months | 
| Changes in vascular strain | Changes in cardiovascular function measured by vascular strain in % | Baseline, followed at 1, 6 and 12 months | 
| Changes in peripheral perfusion determined by ABI (ankle brachial index) | ABI measurements are conducted using a Doppler probe on tibial and anterior artery locations. The highest value will be used for calculation and divided by the highest systolic brachial Doppler pressure | Baseline, followed at 1, 6 and 12 months | 
| Primary patency (PP) of target lesion | Primary patency determined by PVR measurement with ultrasound | Baseline, followed at 1, 6 and 12 months | 
| Changes in clinical symptoms | Clinical symptoms of patients determined by Walking impairment questionaire (WIQ) | Baseline, followed at 1, 6 and 12 months | 
| Changes in six-minute walk test | Six-minute walk test determined by pain-free walking distance in m | Baseline, followed at 1, 6 and 12 months | 
| Procedural complications | Any procedural complications | Baseline, followed at 1, 6 and 12 months | 
| Freedom from Target Lesion Revascularization | Freedom from Target Lesion Revascularization (FTLR) | Baseline, followed at 1, 6 and 12 months | 
| MALE | Any unplanned vascular event and minor or major amputations | Baseline, followed at 1, 6 and 12 months | 
| Changes of inflammatory profile measured by hs-CRP in mg/dl | Blood samples are collected at the below mentioned time points | Baseline, followed at 1, 6 and 12 months | 
| Changes of inflammatory profile measured by oxLDL in µg/l | Blood samples are collected at the below mentioned time points | Baseline, followed at 1, 6 and 12 months | 
| Changes of inflammatory profile measured by Interleukin-6 in pg/ml | Blood samples are collected at the below mentioned time points | Baseline, followed at 1, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paclitaxel eluting ballon, Sirolimus eluting ballon, Percutaneous transluminal angioplasty