Lutonix® Drug Coated Balloon vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal In-Stent Restenosis

Study Overview
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Brief Summary
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To assess the safety and efficacy of the Lutonix Drug Coated Balloon for treatment of femoropopliteal artery (SFA) in-stent restenosis (ISR).

Official Title
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A Prospective, Multicenter, Single-Blind, Randomized, Controlled Trial Comparing the Lutonix® Drug Coated Balloon vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal In-Stent Restenosis

Conditions
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Femoral Artery Stenosis, Femoral Artery Occlusion, Restenosis

Intervention / Treatment
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* Device: Lutonix DCB
* Device: Standard Uncoated Balloon Angioplasty Catheter


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or non-pregnant female ≥18 years of age Rutherford Clinical Category 2-4 Significant (≥ 50%) restenosis of a previous bare (not covered and not drug-eluting) nitinol stent(s) in the femoropopliteal artery Lesion measures between 4 and 18 cm Target vessel diameter between ≥4 and ≤6 mm and able to be treated with available device size matrix A patent inflow artery free from significant lesion (≥50% stenosis) as confirmed by angiography Successful crossing and predilatation of the target lesion with a guidewire At least one patent native outflow artery to the ankle, free from significant (≥50%) stenosis as confirmed by angiography that has not previously been (nor planned to be) revascularized No other prior vascular or surgical interventions within 2 weeks before and/or planned 30 days after the protocol treatment Key Exclusion Criteria: Life expectancy of <1 year Patient is currently participating in an investigational drug or other device study or previously enrolled in this study NOTE: Enrollment in another drug or device clinical trial during the follow up period is not allowed History of stroke within 3 months History of MI, thrombolysis or angina within 2 weeks of enrollment Prior vascular surgery of the index limb, with the exception of remote common femoral patch angioplasty separated by at least 2 cm from the target lesion Target lesion involves a previously placed covered stent or drug-eluting stent Grade 4 or 5 stent fracture (mal-aligned components or trans-axial spiral configuration) in the restenotic stent Inability to take required study medications or allergy to contrast that cannot be adequately managed with pre- and post-procedure medication Known inadequate distal outflow (>50 % stenosis of distal popliteal and/or all three tibial vessels), or planned future treatment of vascular disease distal to the target lesion Intended use of adjunctive treatment modalities (i.e. laser, atherectomy, cryoplasty, scoring/cutting balloon, stents, etc.)

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lutonix DCB<br>Lutonix Paclitaxel Drug Coated Balloon | Device: Lutonix DCB<br> <br> |
| Active Comparator: PTA Catheter<br>Standard Uncoated Balloon Angioplasty Catheter | Device: Standard Uncoated Balloon Angioplasty Catheter<br>* PTA Catheter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Primary Patency at 1 Year | Primary patency is defined as freedom from clinically driven target lesion restenosis (TLR) and from Binary Restenosis. | 12 Months | 
| Percentage of Participants Without Primary Safety Events | Primary Safety Events include: All Cause Perioperative (≤30 day) Death, Index Limb Amputation, Index Limb Reintervention and Index Limb Related Death at 1 Year | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Device Success | Device success is defined as, on 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. | During the Index Procedure (90 mins) | 
| Percentage of Participants With Technical Success | Technical success of the balloon procedure is defined as the achievement of successful delivery and deployment of the study device(s) as intended at the intended target lesion and a successful withdrawal of the study system with the achievement of < 30% residual percent stenosis without deployment of a bail-out stent. | During the Index Procedure (90 mins) | 
| Percentage of Participants With Procedural Success | Procedural Success is defined as attainment of ≤30% residual stenosis in the treatment area by independent core lab analysis without major adverse events (defined as occurrence of death, amputation of the target limb, or repeat revascularization of the target lesion) during the index procedure and through the hospital stay. | During the Index Procedure (90 mins) | 
| Percentage of Participants With Primary Patency at 6 and 12 Months | Primary Patency is defined as Freedom from CEC-adjudicated Clinically-Driven TLR and from Core laboratory-adjudicated Binary Restenosis. Binary restenosis is based on threshold Doppler peak systolic velocity ratio (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). | 6 months and 12 months | 
| Percentage of Participants With Secondary Patency at 6 Months and 12 Months | Secondary patency is defined as the absence of Binary Restenosis as adjudicated by the blinded, independent core laboratory, independent of whether or not patency is re-established via an endovascular procedure. | 6 months and 12 months | 
| Percentage of Participants Without Clinically Driven Target Lesion Revascularization (TLR) | Clinically-driven TLR is defined as revascularization of the target vessel with evidence of target vessel 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), OR revascularization of a target vessel with an in-lesion diameter stenosis of >70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms. | 6 months and 12 months | 
| Percentage of Participants Without Target Lesion Revascularization (TLR) | TLR is defined as any repeat revascularization procedure (percutaneous or surgical) of the original target lesion site. | 6 months and 12 months | 
| Percentage of Participants With Sustained Clinical Benefit Compared to Baseline | Sustained clinical benefit is defined as an improvement in Rutherford Classification compared to baseline and freedom from target vessel revascularization. The Rutherford classification is a clinical means of describing peripheral artery disease along a seven-stage scale, with stage 0 representing asymptomatic presentation and stage 6 representing severe ischemic ulcers or frank gangrene. A decrease in units on the scale represents improvement in clinical symptoms. | 6 months and 12 months | 
| Change of Rutherford Classification From Baseline | The Rutherford classification is a clinical means of describing peripheral artery disease along a seven-stage scale, with stage 0 representing asymptomatic presentation and stage 6 representing severe ischemic ulcers or frank gangrene. A decrease in units on the scale represents improvement in clinical symptoms. | 6 months and 12 months | 
| Change of Resting Ankle Brachial Index (ABI) From Baseline | The ankle-brachial index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure in the upper arm (brachium). | 6 months and 12 months | 
| Change in Walking Impairment Questionnaire From Baseline | The Walking Impairment Questionnaire (WIQ) is a validated questionnaire that evaluates walking ability with a focus on walking distance, walking speed, and the ability to climb stairs. Participants answer each item on a Likert scale from 0 for unable to do to 4 for no difficulty, and each response is weighted based on the difficulty of the task. The overall score is determined by dividing the weighted answers by the maximum possible weighted score and multiplying by 100. The overall score ranges from 0-100 with lower scores indicating lower performance. | 6 months and 12 months | 
| Change in Quality of Life From Baseline | EQ-5D is a standardized tool to assess patient-reported mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, or slight, moderate, severe, or extreme problems. Patients choose the appropriate level in each of the 5 dimensions, which results in a 1-digit number for each dimension. The digits for the 5 dimensions are converted into a single EQ-5D™ index score based on a set of population-based preference weights. For the U.S. general population, possible EQ-5D™ index scores range from -0.11 (i.e., 33333) to 1.0 (i.e., 11111) on a scale where 0.0 = death and 1.0 = perfect health. A downloadable scoring file is available at: https://www.ahrq.gov/rice/EQ5Dscore.htm. The EQ VAS records a patient's self-rated health on a vertical visual analogue scale, where the endpoints are labeled 'The best health you can imagine' (100) and 'The worst health you can imagine' (0). A higher VAS value indicates a higher quality of life. | 6 months and 12 Months | 
| Percentage of Participants Without Major Vascular Complications (≤30 Day) | Freedom from major vascular complications at 30 days follow-up | 30 Days | 
| Percentage of Participants Without All-Cause Death | Mortality from any cause. | 1 month, 6 months, and 12 months | 
| Percentage of Participants Without Major Limb Amputation | Major limb amputation is defined as amputation of the lower limb above the ankle. | 1 month, 6 months, and 12 months | 
| Percentage of Participants Without Minor Limb Amputation | Minor limb amputation is defined as amputation of a part of the foot below the ankle. | 1 month, 6 months, and 12 months | 
| Percentage of Participants Without Target Vessel Revascularizations (TVR) | A TVR is defined as a repeat revascularization procedure (percutaneous or surgical) of a lesion in the target vessel. | 1 month, 6 months, and 12 months | 
| Percentage of Participants Without Any Target Limb Reinterventions | Any surgical intervention in the target limb. | 1 month, 6 months, and 12 months |