Safety and Performance Study of the Shockwave Lithoplasty System

Study Overview
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Brief Summary
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To study the safety and performance of the Shockwave Medical Lithoplasty System in subjects to demonstrate that the Shockwave device can safely and effectively deliver localized shockwave energy for balloon dilatation of calcified, stenotic, infrainguinal peripheral arteries.

Detailed Description
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Shockwave Medical, Inc. intends to conduct a prospective, single-arm, multi-center, clinical study designed to evaluate the safety and performance of the Shockwave Lithoplasty System in subjects with moderate to heavily calcified peripheral arteries with 3.50mm to 7.0mm reference vessel diameter at the target site. The Shockwave Lithoplasty System is indicated to generate sonic shockwave energy within the target treatment site and disrupt calcium within the lesion to allow for subsequent dilation of a peripheral artery stenosis using low balloon pressure. Up to thirty-five (35) subjects will be enrolled and treated with Lithoplasty to yield thirty (30) evaluable subjects complete the study assuming a 15% lost to follow-up rate.

Official Title
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Safety and Performance Study of the Shockwave Lithoplasty System

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Device: Shockwave Lithoplasty System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is able and willing to comply with all assessments in the study. Subject or subject's legal representative have been informed of the nature of the study, agrees to participate and has signed the approved consent form. Age of subject is >18. Rutherford Clinical Category 2, 3, or 4. Resting ankle-brachial index (ABI) of ≤0.90, or ≤0.75 after exercise, of the target leg. Moderate to severe calcification of target lesion(s) per pre-procedure CT scan. (Calcification must be: 1) ≥180 degrees circumferential at some point in the lesion and 2) extend ≥50 percent length of lesion or absolute length ≥20mm.) Estimated life expectancy >1 year. Exclusion Criteria: Rutherford Clinical Category 5 and 6. Subject has active infection in the target leg. Planned major amputation of the target leg (transmetatarsal or higher). In-stent restenosis within the target lesion(s). Highly tortuous arteries (bends greater than 30 degrees over the arc length of the balloon). Chronic total occlusion of the target lesion(s). Target lesion(s) within native or synthetic vessel grafts. Chronic total occlusion of inflow vessel. Lesion in contralateral limb requiring intervention within the next 30 days. History of prior endovascular or surgical procedure on the index limb within the past 30 days. Subject has significant stenosis (>50% stenosis) or occlusion of inflow tract (upstream disease) not successfully treated with plain old balloon angioplasty or stent and without complications before target lesion(s) treatment. Subject requires treatment of a peripheral lesion on the ipsilateral limb distal to the target lesion(s) at the time of the enrollment / index procedure. Subject has a known coagulopathy or has a bleeding diatheses, thrombocytopenia with platelet count less than 100,000/microliter, or international normalized ratio >1.5. Subject in whom antiplatelet, anticoagulant, or thrombolytic therapy is contraindicated. Subject has known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pre-treated. Subject has known allergy to urethane, nylon, or silicone. Myocardial infarction within 60 days prior to enrollment. History of stroke within 60 days prior to enrollment. History of unstable coronary artery disease or other uncontrollable comorbidity resulting in hospitalization within the last 60 days prior to enrollment. History of thrombolytic therapy within two weeks of enrollment. Subject has acute or chronic renal disease (e.g., as measured by a serum creatinine of >2.5 mg/dL or >220 umol/L), or on dialysis. Subject is pregnant or nursing. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint. Subject has other medical, social or psychological problems that, in the opinion of the investigator, preclude them from receiving this treatment, and the procedures and evaluations pre- and post-treatment.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithoplasty Treatment<br>Shockwave Lithoplasty System | Device: Shockwave Lithoplasty System<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of New-onset Major Adverse Events (MAE) | Need for emergency surgical revascularization of target limb. Unplanned target limb amputation (above the ankle). Symptomatic thrombus or distal emboli, defined as clinical signs or symptoms of thrombus or distal emboli detected in the treated limb in the area of the treated lesion, or distal to the treated lesion, after the index procedure or noted angiographically, and requiring mechanical or pharmacologic means to improve flow. Perforations and dissections of grade D or greater that require an intervention to resolve, including bail-out stenting. | 30 days | 
| Procedural Success: | The ability of the Shockwave Medical Lithoplasty System to achieve a post-Shockwave residual diameter stenosis of <50% (with or without adjunctive Percutaneous Transluminal Angioplasty therapy) as assessed by quantitative angiography via core lab evaluation. | Day of Procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success | The ability of the Shockwave Medical Lithoplasty System to achieve a post-Shockwave residual diameter stenosis of <50% (without adjunctive percutaneous transluminal angioplasty therapy) as assessed via quantitative angiography via core lab evaluation. | Day of Procedure | 
| Clinical Success: | The ability of the Shockwave Medical Lithoplasty System to achieve a post-Shockwave residual diameter stenosis of <50% (with or without adjunctive percutaneous transluminal angioplasty therapy) as assessed by the investigator via visual estimate and freedom from procedural major adverse events. | Day of Procedure | 
| Technical Success: | The ability of the Shockwave Medical Lithoplasty System to delivery ShockWave treatment to the desired location in the target vessel. Up to two Shockwave Medical Lithoplasty Systems maybe used to complete treatment in the target vessel. | Day of Procedure | 
| Freedom From Major Adverse Events | Freedom from Major Adverse Events at 30 days. | 30 days | 
| Freedom From Target Lesion Revascularization (TLR) | Freedom from Target Lesion Revascularization (TLR) at 30 days | 30 days | 
| Patency | Vessel patency at 30 days by Doppler Ultrasound defined as freedom from greater than 50% restenosis (as assessed by Duplex ultrasound peak systolic velocity ratio of ≥2.5). | 30 days | 
| Ankle Brachial Index (ABI) | Change in Ankle Brachial Index (ABI) of the target limb at 30 days. The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. | Baseline and 30 days | 
| Rutherford Clinical Category | Change in Rutherford Clinical Category (RCC) at 30 days. RCC identifies three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. Grade I includes Category 0 - Asymptomatic, Category 1 - Mild claudication, Category 2 - Moderate claudication, and Category 3 - Severe claudication. Grade II includes Category 4 - Ischemic rest pain and Category 5 - Minor tissue loss. Grade III includes Category 6 - Ulceration or grangrene. Change of at least 2 categories considered statistically significant. | Baseline and 30 days | 
| Freedom From Major Adverse Events | Freedom from Major Adverse Events at 6 months | 6 months | 
| Freedom From Target Lesion Revascularization (TLR) | Freedom from Target Lesion Revascularization (TLR) at 6 months | 6 months | 
| Patency | Vessel patency at 6 months at Doppler Ultrasound defined as freedom from greater than 50% restenosis (as assessed by Duplex ultrasound peak systolic velocity ratio of =2.5). | 6 months | 
| Ankle Brachial Index (ABI) | Change in Ankle Brachial Index (ABI) of the target limb at 6 months. The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. | Baseline and 6 months | 
| Rutherford Clinical Category | Change in Rutherford Clinical Category (RCC) at 6 months. RCC identifies three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. Grade I includes Category 0 - Asymptomatic, Category 1 - Mild claudication, Category 2 - Moderate claudication, and Category 3 - Severe claudication. Grade II includes Category 4 - Ischemic rest pain and Category 5 - Minor tissue loss. Grade III includes Category 6 - Ulceration or grangrene. Change of at least 2 categories considered statistically significant. | Baseline and 6 months |