ILLUMENATE Pivotal Post-Approval Study (PAS)

Study Overview
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Brief Summary
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The ILLUMENATE Pivotal PAS is a continued follow-up study which will include 300 subjects from forty-three (43) sites across the United States and Austria previously enrolled in the ILLUMENATE Pivotal pre-market study to evaluate the Stellarex DCB compared to the PTA control device for the treatment of de-novo or post-PTA occluded/stenotic or reoccluded/restenotic (except for in-stent) SFA and/or popliteal arteries.

Detailed Description
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The objective of this continued follow-up of ILLUMENATE Pivotal Study subjects is to demonstrate the long term safety and effectiveness of the Stellarex DCB. Each enrolled subject will be followed for 5 years (60 months) after treatment. A follow-up office visit will occur at 24 and 36 months. A follow-up telephone contact or an optional office visit will occur at 48 and 60 months.

Official Title
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ProspectIve, Randomized, SingLe-Blind, U.S. MuLti-Center Study to EvalUate TreatMent of Obstructive SupErficial Femoral Artery or Popliteal LesioNs With A Novel PacliTaxel-CoatEd Percutaneous Angioplasty Balloon Pivotal Post-Approval Study

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Device: Stellarex 0.035 OTW Drug-coated Angioplasty Balloon
* Device: EverCross™ 0.035 PTA Balloon Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - From ILLUMENATE Pivotal IDE population TP-1397E Study subjects must fulfill the following clinical criteria: Symptomatic leg ischemia, requiring treatment of the superficial femoral artery (SFA) and/or popliteal artery. Greater than or equal to 18 years of age. Willing to provide written informed consent, and capable and willing to comply with all required follow-up evaluations within the defined follow-up visit windows. Will not undergo other planned vascular interventions within 14 days before and/or 30 days after the protocol treatment (successful treatment of ipsilateral and contralateral iliac permitted prior to enrollment). Life expectancy >1 year. Rutherford-Becker classification of 2, 3 or 4. Study Subjects must fulfill the following angiographic criteria: De novo or restenotic lesion (except for in-stent restenotic lesion) >70% within the SFA and/or popliteal artery in a single limb. Single lesion which is ≥3 cm and ≤18cm in length (by visual estimation). NOTE: Tandem lesions can be treated. A tandem lesion is defined as two distinct lesions with 3 cm or less of healthy vessel separating the two diseased areas. The total cumulative length of the tandem lesions, including the healthy vessel, must not exceed 18 cm. Lesion is treatable by no more than two (2) study devices. Successful wire crossing of the lesion. The guidewire advancement should not be indicative of the presence of fresh thrombus in the lesion. Target reference vessel diameter is ≥4 mm and ≤6 mm (by visual estimation). Inflow artery is patent, free from significant lesion stenosis (≥50% stenosis is considered significant) as confirmed by angiography. Treatment of a target lesion is acceptable after successful treatment of inflow artery lesion(s). NOTE: Successful inflow artery treatment is defined as attainment of residual diameter stenosis <30% without death or major vascular complication. Target limb with at least one patent (less than 50% stenosis) tibio-peroneal run-off vessel confirmed by baseline angiography or prior magnetic resonance (MR) angiography or computed tomography (CT) angiography (within 45 days prior to index procedure). NOTE: treatment of outflow disease is NOT permitted. Exclusion Criteria - Subject with any of the following clinical criteria should be excluded: Females who are pregnant, lactating, or intend to become pregnant, or males who intend to father children during study participation. Known aortic aneurysm(s) > 5 cm. Contraindication to dual anti-platelet therapy. Known intolerance to study medications, paclitaxel or contrast agents that in the opinion of the investigator cannot be adequately pre-treated. Current participation in an investigational drug or another device study. History of hemorrhagic stroke within 3 months. Previous or planned surgical or interventional procedure within 14 days before or 30 days after the index procedure (successful treatment of ipsilateral and contralateral iliac permitted prior to enrollment). Prior endovascular treatment of target lesion by percutaneous transluminal angioplasty or any other means of previous endovascular treatment (e.g. stents/stent grafts, cutting balloon, scoring balloon, cryoplasty, thrombectomy, atherectomy, brachytherapy or laser devices) within six months of the index procedure, or any previous placement of a bypass graft proximal to the target lesion. Treatment of lesions in the contralateral limb with the CVI Paclitaxel-coated PTA Catheter. Use of the CVI Paclitaxel-coated PTA Catheter in other than a single treatment session. Chronic renal insufficiency (dialysis dependent, or serum creatinine >2.5 mg/dL within 30 days of index procedure). Subject with any of the following angiographic criteria should be excluded: Significant contralateral or ipsilateral common femoral disease that requires intervention during the index procedure. No normal proximal arterial segment of the target vessel in which duplex ultrasound velocity ratios can be measured. Known inadequate distal outflow. Acute or sub-acute thrombus in the target vessel. Aneurysmal target vessel. Use of adjunctive therapies (i.e. laser, atherectomy, cryoplasty, scoring/cutting balloons, brachytherapy) during the index procedure in the target lesion or target vessel. Treatment of the contralateral limb during the same procedure or within 30 days following the study procedure (exclusive of the iliac arteries which can be treated prior to enrollment). Presence of concentric calcification that precludes PTA pre-dilation. Prior stent placement in the target vessel. Residual stenosis of greater than 70%, stent placement or flow-limiting (Grade D or greater) dissection following pre-dilation.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCB Subjects<br>The Stellarex DCB is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Medtronic, Plymouth, MN 55441, USA) coated with paclitaxel using a proprietary carrier. Basic Catheter Specifications Guidewire: 0.035 Balloon Length: 40/80/120 mm Sheath Compatibility: greater than or equal to 6 French Balloon Diameter: 4/5/6 mm Shaft length: 135 cm The nominal dose density of paclitaxel on the Stellarex DCB is 2.0 μg/mm2. Indications The Stellarex 0.035 OTW Drug-coated Angioplasty Balloon is indicated for percutaneous transluminal angioplasty (PTA), after appropriate vessel preparation, of de novo or restenotic lesions up to 180 mm in length in native superficial femoral or popliteal arteries with reference vessel diameters of 4-6 mm. | Device: Stellarex 0.035 OTW Drug-coated Angioplasty Balloon<br>* The Stellarex 0.035 OTW Drug-coated Angioplasty Balloon is indicated for percutaneous transluminal angioplasty (PTA), after appropriate vessel preparation, of de novo or restenotic lesions up to 180 mm in length in native superficial femoral or popliteal arteries with reference vessel diameters of 4-6 mm.<br>|
| Placebo Comparator: PTA Subjects<br>The control device is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Medtronic, Plymouth, MN 55441, USA). Basic Catheter Specifications Guidewire: 0.035 Balloon Length: 40/80/120 mm Sheath Compatibility: greater to or equal to 6 French Balloon Diameter: 4/5/6 mm Shaft length: 135 cm Indications The EverCross Balloon Catheter is intended to dilate stenosis in the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, and renal arteries, and to treat obstructive lesions of native or synthetic arteriovenous dialysis fistulae. This device is also indicated for stent post-dilation in the peripheral vasculature. For additional information refer to the EverCross Instructions for Use. | Device: EverCross™ 0.035 PTA Balloon Catheter<br>* The control device is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA Balloon Catheter, Medtronic, Plymouth, MN 55441, USA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target vessel patency at 24 months post-procedure | Patency is defined as the absence of target lesion restenosis as determined by duplex ultrasound (Peak Systolic Velocity Ratio (PSVR) ≤ 2.5) and freedom from clinically-driven target lesion revascularization. | 24 months post-procedure | 
| Freedom from target limb major amputation and clinically-driven target lesion revascularization through 24 months post-procedure | Freedom from target limb major amputation and clinically-driven target lesion revascularization through 24 months post-procedure. | 24 months post-procedure | 
| Freedom from device and procedure-related death through 30 days post-procedure | Freedom from device and procedure-related death through 30 days post-procedure | 30 days post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse event (MAE) rate at 24 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR) | Major adverse event (MAE) rate at 24 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR). | 24 months post-procedure | 
| Major adverse event (MAE) rate at 36 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR) | Major adverse event (MAE) rate at 36 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR). | 36 months post-procedure | 
| Major adverse event (MAE) rate at 48 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR) | Major adverse event (MAE) rate at 48 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR). | 48 months post-procedure | 
| Major adverse event (MAE) rate at 60 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR) | Major adverse event (MAE) rate at 60 months post-procedure, defined as a composite rate of cardiovascular death, target limb major amputation and clinically-driven target lesion revascularization (TLR). | 60 months post-procedure | 
| Rate of clinically-driven target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 24 months post-procedure | 
| Rate of clinically-driven target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 36 months post-procedure | 
| Rate of clinically-driven target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 48 months post-procedure | 
| Rate of clinically-driven target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 60 months post-procedure | 
| Rate of target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 24 months post-procedure | 
| Rate of target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 36 months post-procedure | 
| Rate of target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 48 months post-procedure | 
| Rate of target lesion revascularization | Lesion revascularization occuring in the target lesion deemed clinically driven by the Clinical Events Committee | 60 months post-procedure | 
| Rate of clinically-driven target vessel revascularization | Lesion revascularization occuring in the target vessel deemed clinically driven by the Clinical Events Committee | 24 months post-procedure | 
| Rate of clinically-driven target vessel revascularization | Lesion revascularization occuring in the target vessel deemed clinically driven by the Clinical Events Committee | 36 months post-procedure | 
| Rate of clinically-driven target vessel revascularization | Lesion revascularization occuring in the target vessel deemed clinically driven by the Clinical Events Committee | 48 months post-procedure | 
| Rate of clinically-driven target vessel revascularization | Lesion revascularization occuring in the target vessel deemed clinically driven by the Clinical Events Committee | 60 months post-procedure | 
| Rate of target limb major amputation | Number of subjects in which a major amputation occurred in the target limb | 24 months post-procedure | 
| Rate of target limb major amputation | Number of subjects in which a major amputation occurred in the target limb | 36 months post-procedure | 
| Rate of target limb major amputation | Number of subjects in which a major amputation occurred in the target limb | 48 months post-procedure | 
| Rate of target limb major amputation | Number of subjects in which a major amputation occurred in the target limb | 60 months post-procedure | 
| Mortality rate | Number of subject who have died during the post-procedure follow up period | 24 months post-procedure | 
| Mortality rate | Number of subject who have died during the post-procedure follow up period | 36 months post-procedure | 
| Mortality rate | Number of subject who have died during the post-procedure follow up period | 48 months post-procedure | 
| Mortality rate | Number of subject who have died during the post-procedure follow up period | 60 months post-procedure | 
| Rate of occurrence of arterial thrombosis of the treated segment | Rate of occurrence of arterial thrombosis of the treated segment | 24 months post-procedure | 
| Rate of occurrence of arterial thrombosis of the treated segment | Rate of occurrence of arterial thrombosis of the treated segment | 36 months post-procedure | 
| Rate of occurrence of arterial thrombosis of the treated segment | Rate of occurrence of arterial thrombosis of the treated segment | 48 months post-procedure | 
| Rate of occurrence of arterial thrombosis of the treated segment | Rate of occurrence of arterial thrombosis of the treated segment | 60 months post-procedure | 
| Patency rate defined as the absence of target lesion restenosis as determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven TLR | Patency rate defined as the absence of target lesion restenosis as determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven TLR | 24 months post-procedure | 
| Patency rate defined as the absence of target lesion restenosis as determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven TLR | Patency rate defined as the absence of target lesion restenosis as determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven TLR | 36 months post-procedure | 
| Change in ankle-brachial index (ABI) from pre-procedure | The ankle-brachial index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure in the upper arm (brachium). The normal range for the ankle-brachial index is between 0.90 and 1.30. An index under 0.90 means that blood is having a hard time getting to the legs and feet: 0.41 to 0.90 indicates mild to moderate peripheral artery disease; 0.40 and lower indicates severe disease. | 24 months post-procedure | 
| Change in ankle-brachial index (ABI) from pre-procedure | The ankle-brachial index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure in the upper arm (brachium). The normal range for the ankle-brachial index is between 0.90 and 1.30. An index under 0.90 means that blood is having a hard time getting to the legs and feet: 0.41 to 0.90 indicates mild to moderate peripheral artery disease; 0.40 and lower indicates severe disease. | 36 months post-procedure | 
| Change in walking impairment questionnaire (WIQ) from pre-procedure | A disease-specific instrument utilized to characterize walking ability through a questionnaire. It is a measure of patient-perceived walking performance for patients with PAD and/or intermittent claudication | 24 months post-procedure | 
| Change in walking impairment questionnaire (WIQ) from pre-procedure | A disease-specific instrument utilized to characterize walking ability through a questionnaire. It is a measure of patient-perceived walking performance for patients with PAD and/or intermittent claudication | 36 months post-procedure | 
| Change in walking distance from pre-procedure | Distance in meters or feet traveled in 6 minutes measured at pre-procedure and at 24 month office visit. | 24 months post-procedure | 
| Change in walking distance from pre-procedure | Distance in meters or feet traveled in 6 minutes measured at pre-procedure and at 36 month office visit. | 36 months post-procedure | 
| Change in Rutherford-Becker classification from pre-procedure | Rutherford-Becker Classification is a classification system of Peripheral Arterial Disease, the higher the number the worse the disease. Category Clinical Description 0-Asymptomatic--no hemodynamically significant occlusive disease Mild claudication Moderate claudication Severe claudication 4*-Ischemic rest pain 5*-Minor tissue loss-nonhealing ulcer, focal gangrene with diffuse pedal ischemia 6*-Major tissue loss-extending above transmetatarsal level, functional foot no longer salvageable *Categories 4, 5, and 6 are also described as critical limb ischemia. | 24 months post-procedure | 
| Change in Rutherford-Becker classification from pre-procedure | Rutherford-Becker Classification is a classification system of Peripheral Arterial Disease, the higher the number the worse the disease. Category Clinical Description 0-Asymptomatic--no hemodynamically significant occlusive disease Mild claudication Moderate claudication Severe claudication 4*-Ischemic rest pain 5*-Minor tissue loss-nonhealing ulcer, focal gangrene with diffuse pedal ischemia 6*-Major tissue loss-extending above transmetatarsal level, functional foot no longer salvageable *Categories 4, 5, and 6 are also described as critical limb ischemia. | 36 months post-procedure | 
| Change in EQ-5D from pre-procedure | EQ-5D is designed for self-completion by subjects and is intended to reflect the health status at the time of completion. | 24 months post-procedure | 
| Change in EQ-5D from pre-procedure | EQ-5D is designed for self-completion by subjects and is intended to reflect the health status at the time of completion. | 36 months post-procedure |