Safety and Efficacy of the SurVeil™ Drug-Coated Balloon

Study Overview
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Brief Summary
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To demonstrate the safety and efficacy of the SurVeil Drug-Coated Balloon (DCB) for treatment of subjects with symptomatic peripheral artery disease (PAD) due to stenosis of the femoral and/or popliteal arteries.

Detailed Description
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TRANSCEND is a prospective, multi-center, single-blind, randomized, controlled, noninferiority clinical trial. The trial will randomize approximately 446 subjects with symptomatic PAD due to stenoses of the femoral and/or popliteal arteries. Subjects meeting eligibility criteria will be randomized 1:1 to treatment with either the SurVeil DCB or the IN.PACT Admiral DCB, and followed for 60 months.

Official Title
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The Randomized And Controlled Noninferiority Trial to Evaluate Safety and Clinical Efficacy of the SurVeil™ Drug-Coated Balloon iN the Treatment of Subjects With Stenotic Lesions of the Femoropopliteal Artery Compared to the Medtronic IN.PACT® Admiral® Drug-Coated Balloon

Conditions
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Peripheral Arterial Disease, Peripheral Vascular Disease, Artery Disease, Peripheral, Femoropopliteal Artery Occlusion

Intervention / Treatment
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* Device: Surmodics SurVeil DCB
* Device: Medtronic IN.PACT Admiral DCB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥18 years. Subject has target limb Rutherford classification 2, 3 or 4. Subject has provided written informed consent and is willing to comply with study follow-up requirements. De novo lesion(s) or non-stented restenotic lesion(s) occurring >90 days after prior plain old balloon (POBA) angioplasty or >180 days after prior DCB treatment. Target lesion location starts ≥10 mm below the common femoral bifurcation and terminates distally at or above the end of the P1 segment of the popliteal artery. Target vessel diameter ≥4 mm and ≤7 mm. Target lesion must have angiographic evidence of ≥70% stenosis by operator visual estimate. Chronic total occlusions may be included only after successful, uncomplicated wire crossing of target lesion via an anterograde approach and without the use of subintimal dissection techniques. Target lesion must be ≤180 mm in length (one long lesion or multiple serial lesions) by operator visual estimate. Note: combination lesions must have a total lesion length of ≤180 mm by visual estimate and be separated by ≤30 mm. Target lesion is located at least 30 mm from any stent, if target vessel was previously stented. Successful, uncomplicated (without use of a crossing device) wire crossing of target lesion. Successful crossing of the target lesion occurs when the tip of the guide wire is distal to the target lesion without the occurrence of flow-limiting dissection or perforation and is judged by visual inspection to be within the true lumen. After pre-dilatation, the target lesion is ≤70% residual stenosis, absence of a flow limiting dissection and treatable with available device matrix. A patent inflow artery free from significant stenosis (≥50% stenosis) as confirmed by angiography. At least one patent native outflow artery to the ankle or foot, free from significant stenosis (≥50% stenosis) as confirmed by angiography. Exclusion Criteria: Subject has acute limb ischemia. Subject underwent percutaneous transluminal angioplasty (PTA) of the target limb using plain old balloon angioplasty (POBA) or a stent within the previous 90 days. Subject underwent any lower extremity percutaneous treatment using a paclitaxel-eluting stent or a DCB within the previous 90 days. Subject underwent PTA of the target lesion using a DCB within the previous 180 days. Subject has had prior vascular intervention in the contralateral limb within 14 days before the planned study index procedure or subject has planned vascular intervention in the contralateral limb within 30 days after the index procedure. Subject is pregnant, breast-feeding or intends to become pregnant during the time of the study. Subject has life expectancy less than 2 years. Subject has a known allergy to contrast medium that cannot be adequately pre-medicated. Subject is allergic to ALL antiplatelet treatments. Subject has impaired renal function (i.e. serum creatinine level ≥2.5 mg/dL). Subject is dialysis dependent. Subject is receiving immunosuppressant therapy. Subject has known or suspected active infection at the time of the index procedure. Subject has platelet count <100,000/mm3 or >700,000/mm3. Subject has history of gastrointestinal hemorrhage requiring a transfusion within 3 months prior to the study procedure. Subject is diagnosed with coagulopathy that precludes treatment with systemic anticoagulation and/or dual antiplatelet therapy (DAPT). Subject has history of stroke within the past 90 days. Subject has a history of myocardial infarction within the past 30 days. Subject is unable to tolerate blood transfusions because of religious beliefs or other reasons. Subject is incarcerated, mentally incompetent, or abusing drugs or alcohol. Subject is participating in another investigational drug or medical device study that has not completed primary endpoint(s) evaluation or that clinically interferes with the endpoints from this study, or subject is planning to participate in such studies prior to the completion of this study. Subject has had any major (e.g. cardiac, peripheral, abdominal) surgical procedure or intervention unrelated to this study within 30 days prior to the index procedure or has planned major surgical procedure or intervention within 30 days of the index procedure. Subject had previous bypass surgery of the target lesion. Subject had previous treatment of the target vessel with thrombolysis or surgery. Subject is unwilling or unable to comply with procedures specified in the protocol or has difficulty or inability to return for follow-up visits as specified by the protocol. Target lesion has severe calcification (as defined by the PARC classification of calcification). Target lesion involves an aneurysm or is adjacent to an aneurysm (within 5 mm). Target lesion requires treatment with alternative therapy such as stenting, laser, atherectomy, cryoplasty, brachytherapy, re-entry devices, or subintimal dissection techniques. Significant target vessel tortuosity or other parameters prohibiting access to the target lesion. Presence of thrombus in the target vessel. Iliac inflow disease requiring treatment, unless the iliac artery disease is successfully treated first during the index procedure. Success is defined as ≤30% residual diameter stenosis without death or major complications. Presence of an aortic, iliac or femoral artificial graft.

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: Surmodics SurVeil DCB<br>Surmodics SurVeil Drug-Coated Balloon is an investigational device coated with paclitaxel. | Device: Surmodics SurVeil DCB<br>* Angioplasty procedure with a paclitaxel-coated, percutaneous transluminal angioplasty (PTA) balloon catheter.<br>|
| Active Comparator: Medtronic IN.PACT Admiral DCB<br>Angioplasty procedure with a paclitaxel-coated, percutaneous transluminal angioplasty (PTA) balloon catheter. | Device: Medtronic IN.PACT Admiral DCB<br>* Angioplasty procedure with a paclitaxel-coated, percutaneous transluminal angioplasty (PTA) balloon catheter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Lesion Patency | Composite of freedom from clinically-driven target lesion revascularization (TLR) and binary restenosis (restenosis defined as duplex ultrasound [DUS] peak systolic velocity ratio [PSVR] ≥2.4 or ≥50% stenosis as assessed by independent angiographic and DUS core labs) through 12 months post-index procedure. | 12 months | 
| Safety composite of death, amputation, and target vessel revascularization (TVR) | Composite of freedom from device- and procedure-related death through 30 days post-index procedure and freedom from major target limb amputation (above the ankle) and clinically-driven TVR through 12 months post-index procedure. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success | Defined as successful delivery, balloon inflation, deflation and retrieval of the intact study device without burst below rated burst pressure, and achievement of <50% residual stenosis of the target lesion (by core lab-assessed quantitative angiography [QA]) without flow-limiting arterial dissection using only the study device. | Day 0 | 
| Technical Success | Defined as achievement of a final residual diameter stenosis of <50% (by core lab-assessed QA) without flow-limiting arterial dissection at the end of the procedure. | Day 0 | 
| Procedure Success | Defined as evidence of both acute technical success and absence of Peripheral Academic Research Consortium major adverse events (PARC MAEs; e.g., death, stroke, myocardial infarction, acute onset of limb ischemia, index bypass graft or treated segment thrombosis, and or need for urgent/emergent vascular surgery) within 72 hours of the index procedure. | 72 hours | 
| Clinical Success | Freedom from all-cause death, major target limb amputation and TVR through 30 days | 30 days | 
| Primary Lesion Patency | Applicable only if both the primary safety and efficacy hypotheses of noninferiority are met. Primary patency defined as a composite of freedom from clinically-driven target lesion revascularization (TLR) and binary restenosis (restenosis defined as duplex ultrasound [DUS] peak systolic velocity ratio [PSVR] ≥2.4 or ≥50% stenosis as assessed by independent angiographic and DUS core labs). | 24 months | 
| Target Vessel Patency | Defined as freedom from clinically-driven TVR and binary restenosis (restenosis defined as DUS PSVR ≥2.4 or ≥50% stenosis as assessed by independent angiographic and DUS core labs). | 12 months, 24 months | 
| Sustained Clinical Improvement | Defined as freedom from major target limb amputation, TVR and worsening target limb Rutherford class, within 6, 12, and 24 months. | 6 months, 12 months, 24 months | 
| Clinically-driven TLR | Clinically-driven target lesion revascularization, within 6, 12, 24, 36, 48, and 60 months | 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months | 
| Historical MAEs | Major Adverse Events (MAEs) defined as composite of all-cause death, clinically-driven TLR, major target limb amputation, or thrombosis at the target lesion, within 6, 12, 24, 36, 48, and 60 months. | 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months | 
| Major amputation | Major target limb amputation, within 6, 12, 24, 36, 48, and 60 months. | 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months | 
| Thrombosis | Thrombosis at target limb, within 6, 12, 24, 36, 48, and 60 months. | 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months | 
| Rutherford Class | Change in target limb Rutherford class from baseline to 1, 6, 12, and 24 months. | Screening, 1 month, 6 months, 12 months, and 24 months | 
| PARC Class | Change in target limb PARC class from baseline to 1, 6, 12, and 24 months. | Screening, 1 month, 6 months, 12 months, and 24 months | 
| Ankle Brachial Index (ABI) | Decrease in target limb ABI or toe brachial index ≥0.15 from baseline to 6, 12, and 24 months. | Screening, 6 months, 12 months, and 24 months | 
| Walking Impairment Questionnaire (WIQ) | Change in WIQ score from baseline to 1, 12, and 24 months. | Screening, 1 month, 12 months, and 24 months | 
| Six Minute Walk Test (6MWT) | Change in 6MWT from baseline to 12 and 24 months. | Screening, 12 months, and 24 months | 
| Peripheral Artery Questionnaire (PAQ) | Change in PAQ score from baseline to 1, 12, and 24 months. | Screening, 1 month, 12 months, and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous Transluminal Angioplasty, PTA, Peripheral Artery Disease, PAD, Paclitaxel