Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the superior efficacy and non-inferior safety of the Moxy Drug Coated Balloon by direct comparison to standard percutaneous transluminal angioplasty (PTA) catheter for treatment of stenosis of the femoropopliteal arteries.

Detailed Description
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The Moxy Drug Coated Balloon is indicated for percutaneous transluminal angioplasty of obstructive de novo or non-stented restenotic lesions in native femoropopliteal arteries up to 15 cm in length and ≥4.0 to ≤6.0 mm in diameter. This study will randomize approximately 476 patients who will receive either the Moxy balloon or standard balloon angioplasty at 55 global investigational sites. Subjects will be blinded to treatment until 12 months and will participate in long term follow-up for 5 years.

Official Title
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A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial Comparing the Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries

Conditions
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Femoral Artery Stenosis, Popliteal Artery Stenosis, Femoral Artery Occlusion, Popliteal Artery Occlusion

Intervention / Treatment
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* Procedure: Standard Uncoated Angioplasty Balloon
* Device: Moxy Drug Coated Balloon


Participation Criteria
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Eligibility Criteria
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Clinical Inclusion Criteria: Male or non-pregnant female ≥18 years of age; Rutherford Clinical Category 2-4; Patient is willing to provide informed consent, is geographically stable and comply with the required follow up visits, testing schedule and medication regimen; Angiographic Lesion Inclusion Criteria: Length ≤15 cm; Up to two focal lesions or segments within the designated 15 cm length of vessel may be treated (e.g. two discrete segments, separated by several cm, but both falling within a composite length of ≤15 cm); ≥70% stenosis by visual estimate; Lesion location starts ≥1 cm below the common femoral bifurcation and terminates distally ≤2 cm below the tibial plateau AND ≥1 cm above the origin of the TP trunk; de novo lesion(s) or non-stented restenotic lesion(s) >90 days from prior angioplasty procedure; Lesion is located at least 3 cm from any stent, if target vessel was previously stented; Target vessel diameter between ≥4 and ≤6 mm and able to be treated with available device size matrix; Successful, uncomplicated (without use of a crossing device) antegrade wire crossing of lesion; A patent inflow artery free from significant lesion (≥50% stenosis) as confirmed by angiography (treatment of target lesion acceptable after successful treatment of inflow artery lesions); NOTE: Successful inflow artery treatment is defined as attainment of residual diameter stenosis ≤30% without death or major vascular complication. At least one patent native outflow artery to the ankle, free from significant (≥50%) stenosis as confirmed by angiography that has not previously been revascularized (treatment of outflow disease is NOT permitted during the index procedure); Contralateral limb lesion(s) cannot be treated within 2 weeks before and/or planned 30 days after the protocol treatment in order to avoid confounding complications; No other prior vascular interventions within 2 weeks before and/or planned 30 days after the protocol treatment. Exclusion Criteria: Patients will be excluded if ANY of the following conditions apply: Pregnant or planning on becoming pregnant or men intending to father children; Life expectancy of <5 years; Patient is currently participating in an investigational drug or other device study or previously enrolled in this study; NOTE: Enrollment in another clinical trial during the follow up period is not allowed. History of hemorrhagic stroke within 3 months; Previous or planned surgical or interventional procedure within 2 weeks before or within 30 days after the index procedure; History of myocardial infarction (MI), thrombolysis or angina within 2 weeks of enrollment; Rutherford Class 0, 1, 5 or 6; Renal failure or chronic kidney disease with modification in diet in renal disease glomerular filtration rate (MDRD GFR) ≤30 ml/min per 1.73 m2 (or serum creatinine ≥2.5 mg/L within 30 days of index procedure or treated with dialysis); 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; Inability to take required study medications or allergy to contrast that cannot be adequately managed with pre- and post-procedure medication; Anticipated use of IIb/IIIa inhibitor prior to randomization; Ipsilateral retrograde access; Composite lesion length is >15 cm or there is no normal proximal arterial segment in which duplex flow velocity can be measured; Significant inflow disease. Successful treatment of inflow disease allowed prior to target lesion treatment; 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; Sudden symptom onset, acute vessel occlusion, or acute or sub-acute thrombus in target vessel; Severe calcification that renders the lesion un-dilatable; Use of adjunctive treatment modalities (i.e. laser, atherectomy, cryoplasty, scoring/cutting balloon, 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moxy Drug Coated Balloon<br>Paclitaxel coated balloon catheter | Device: Moxy Drug Coated Balloon<br>* Subjects will be randomized 2:1 to the drug coated or standard angioplasty balloon<br>|
| Active Comparator: Standard Uncoated Angioplasty Balloon<br>PTA Catheter | Procedure: Standard Uncoated Angioplasty Balloon<br>* Subjects will be randomized 2:1 to the Moxy Drug Coated Balloon or Standard Angioplasty Balloon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Composite Freedom From All-Cause Peri-Operative (≤30 Day) Death and Freedom From Index Limb Amputation, Index Limb Re-Intervention, and Index-Limb-Related Death at 12 Months Post Index Procedure | Composite of freedom from all-cause peri-operative (≤30 day) death and freedom at 1 year from the following: index limb amputation (above or below the ankle), index limb re-intervention, and index-limb-related death. | 12 months post index procedure | 
| Percentage of Participants With Primary Patency of the Target Lesion at 12 Months Post Index Procedure | Primary Patency is defined as the absence of target lesion restenosis (defined by DUS peak systolic velocity ratio (PSVR) ≥2.5) and freedom from target lesion revascularization (TLR). | 12 months post index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Acute Device Success at Time of Index Procedure | Device Success was defined as 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. | At time of Index Procedure | 
| Number of Participants With Technical and Procedural Success | Technical Success is defined as successful access and deployment of the device and visual estimate of ≤30% diameter residual stenosis during the index procedure without deployment of a bailout stent. Procedural Success is defined as attainment of ≤30% residual stenosis in the treatment area by independent core lab analysis without serious adverse events during the index procedure. | At time of Index Procedure | 
| Number of Participants With Primary Patency at 6, 12, and 24 Months Post Index Procedure | Primary Patency is defined as the absence of target lesion restenosis (defined by core lab adjudication or strict application of PSVR thresholds) and freedom from target lesion revascularization (TLR). | 6, 12, and 24 months post index procedure | 
| Number of Participants With Alternative Primary Patency at 6, 12, and 24 Months Post Index Procedure | Percentage of subjects with Alternative Primary Patency based on alternative definitions of duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) <2.0 and <3.0 at 6, 12, and 24 months post index procedure. DUS PSVR was calculated by dividing the maximum peak systolic velocity (PSV) from the stenosis by the PSV from the nearest segment of normal artery above the site of increase. | 6, 12, and 24 months post index procedure | 
| Number of Participants With Duplex Ultrasound (DUS) Clinical Patency at 6, 12, and 24 Months Post Index Procedure | DUS Clinical Patency defined as DUS PSVR <2.5 without prior clinically driven target lesion revascularization (TLR). | 6, 12, and 24 months post index porcedure | 
| Number of Participants With Freedom From Target Lesion Revascularization (TLR) Clinically-driven at 6, 12, and 24 Months Post Index Procedure |  | 6, 12, and 24 months post index procedure | 
| Improvement in Rutherford Classification Scores at 6, 12, and 24 Months Post Index Procedure Compared to Baseline | The endpoint summarizes the change in index-limb Rutherford Classification of participants from baseline through 24 months. Data is presented as shift from baseline Rutherford Classification data using the following categories: 1) Improvement, 2) Same, and 3) Worsened. | 6, 12, and 24 months post index procedure | 
| Change in Resting Ankle Brachial Index (ABI) at 6, 12, and 24 Months Compared to Baseline | Mean change from baseline values. The Ankle Brachial Index (ABI) is defined as a ratio of ankle to brachial (upper arm) artery systolic blood pressure and aims at determining how well the blood is flowing in the legs. | 6, 12, and 24 months from baseline | 
| Change in Six Minute Walk Test Distance at 6, 12, and 24 Months Compared to Baseline | The data bellow is presented as a Mean change in scores for the Six Minute Walk Test scores at 6, 12, and 24 months compared to baseline. | 6, 12, and 24 months from baseline | 
| Change in European Quality of Life 5 Dimensions (EuroQol -5D) Scores at 6, 12, and 24 Months Compared to Baseline. | Mean change in EuroQol (EQ-5D) scores at 6, 12, and 24 months compared to baseline. The EurolQol-5D system rates quality of life using five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of ratings, that is, no problems, slight problems, moderate problems, severe problems and extreme problems that can be selected. A visual scale allows participants to report their own perception of their health status. The overall scores range from 0 (worst) to 100 (best). Please note that the data in the table below represent the mean changes in overall scores for each group compared to their baseline data. | 6, 12, and 24 months | 
| Change in Score on the Short Form Quality of Life Measure (Physical Component) at 6, 12, and 24 Months Compared to Baseline. | Mean change from Baseline on the Short Form (SF-36 v2) Quality of Life Questionnaire at 6, 12, and 24 months. The SF-36 v2 United States (US) is a brief measure of general health status. The physical health measure of the test comprises four scales, that is, physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The scores range between 0 and 100 (with higher scores indicating better health). In the results presented below, a positive Mean represents an increase in the average health score while a negative Mean represents a decrease in the same mean score compared to baseline measure. | 6, 12, and 24 months | 
| Change in Quality of Life (Mental Component) on the Short-form 36 (SF-36 v2) at 6, 12, and 24 Months Compared to Baseline | Mean change in quality of life (mental component) on Short-form 36 (SF-36 v2) from baseline at 6, 12, and 24 months. The SF-36 v2 United States (US) is a brief measure of general health status. The mental health measure comprises four scales, that is, vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). The scores range from 0 to 100 (with higher scores indicating better health). In the results presented below, a positive Mean represents an increase in the average health score while a negative Mean represents a decrease in the same mean score compared to baseline measure. | 6, 12, and 24 months from baseline | 
| Number of Subjects With Freedom From Death, Index-Limb Amputation, and Target Vessel Revascularization (TVR) at 30 Days Post Index Porcedure | Number of subjects with Freedom from all-cause death, index limb amputation above the ankle and Target Vessel Revascularization (TVR) (VIVA Safety Endpoint) | 30 days post index procedure | 
| Number of Participants With Composite of Freedom From All-Cause Perioperative (<30 Day) Death and Freedom From the Following at 1,6, 24, 36, 48, and 60 Months: Index Limb Amputation, Index Limb Re-intervention, and Index Limb Related Death |  | 1, 6, 24, 36, 48, and 60 months post index procedure | 
| Number of Participants With All Cause Death, Amputation, Target Vessel Revascularization, Reintervention for Thrombosis, Major and Minor Vascular Complications, and Readmission for Cardiovascular Events at 1, 6, 12, 24, 36, 48, and 60 Months PPI. | Amputation defined as above the ankle free survival (AFS). PPI = Post index procedure. | 1, 6, 12, 24, 36, 48, and 60 months post index procedure | 
| Change in Walking Impairment Questionnaire (WIQ) Scores at 6, 12, and 24 Months Post Index Procedure Compared to Baseline. | The WIQ assesses 3 categories of activities that include 1) walking distance, 2) stair-climbing, and 3) walking speed. Each question requires participants to rate their degree of difficulty with the activity on a scale of 0 (unable) to 4 (no problem). Final scores range from 0% to 100%, with lower percentages indicating higher levels of difficulties with activities.The results below represent the mean differences in total Walking Impairment Questionnaire (WIQ) scores at 6, 12, and 24 months, compared to baseline assessment scores. | 6, 12, and 24 months post index procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arms, Experimental, Drug Coated Angioplasty Balloon, Active Comparator, Standard Angioplasty Balloon