Disrupt PAD+ Study With the Shockwave Medical M5+ Peripheral IVL System

Study Overview
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Brief Summary
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Prospective, multi-center, single-arm study of the M5+ Peripheral IVL system to treat calcified peripheral arteries.

Detailed Description
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The objective of this study is to assess the safety and performance of the Shockwave M5+ Peripheral IVL System to treat calcified peripheral arteries in pre-market countries, and to assess continued safety and effectiveness in the US. A minimum of 40 lesions in up to 40 subjects at up to 10 sites in Australia, New Zealand and the US will be enrolled with the aim of treating at least 20 target lesions with the 8.0 mm IVL catheter. A maximum of three target lesions may be treated per subject. Subjects with moderate and severely calcified iliac and femoropopliteal artery disease presenting with Rutherford Category 2 to 5. Approximately 6 months of enrollment at up to 10 sites in Australia, New Zealand and the US. Study subjects will be followed through discharge, 30 days, 6 and 12 months. Duplex Ultrasound (DUS) assessments will be completed at 12 months. Total anticipated study duration is 18 months. The primary safety endpoint is Major Adverse Events (MAE) at 30 days defined as: need for emergency surgical revascularization of target limb; unplanned target limb major amputation (above the ankle); symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization ; or perforations that require an intervention, including bail-out stenting. The primary performance endpoint is technical success defined as final residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion by angiographic core lab.

Official Title
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Prospective, Multi-center, Single-arm Study of the Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) System in Calcified Peripheral Arteries

Conditions
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Peripheral Arterial Disease, Vascular Disease, Peripheral

Intervention / Treatment
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* Device: Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL)


Participation Criteria
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Eligibility Criteria
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General 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, 4 or 5 of the target limb(s). Estimated life expectancy >1 year. Subject is intended to undergo treatment with Shockwave M5+ Peripheral IVL System for de novo lesions of the ilio-femoropopliteal arteries. Angiographic Inclusion Criteria Single or multiple de novo target lesion(s) located from the common iliac to the femoropopliteal artery, in one or both limbs. Target lesion reference vessel diameter is between 3.5mm and 8.0mm by visual estimate. Target lesion is ≥70% stenosis by investigator via visual estimate. Target lesion length is ≤200mm for lesions 70-99% stenosed. Target lesion can be all or part of the 200mm treated zone. Chronic total occlusion, lesion length is ≤100mm of the total ≤200 mm target lesion. Subject has at least one patent tibial vessel on the target leg with runoff to the foot, defined as no stenosis >50%. Calcification is at least moderate defined as presence of fluoroscopic evidence of calcification: 1) on parallel sides of the vessel and 2) extending > 50% the length of the lesion if lesion is ≥50mm in length; or extending for minimum of 20mm if lesion is <50mm in length. General Exclusion Criteria Rutherford Clinical Category 0, 1, and 6. Subject has active infection requiring antibiotic therapy. History of endovascular or surgical procedure on the target limb within the last 30 days or planned within 30 days of the index procedure. Note: Concomitant IVL treatment to facilitate large bore access at the time of procedure is allowed. Subject in whom antiplatelet or anticoagulant 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. Subject has acute or chronic renal disease defined as serum creatinine of >2.5 mg/dL or >220 umol/L, unless 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. The planned use of specialty balloons, re-entry or atherectomy devices in the target lesion(s). Angiographic Exclusion Criteria In-stent restenosis within 10mm of the target zone. Target lesions distal to the popliteal artery. Evidence of aneurysm or thrombus in target vessel. No calcium or mild calcium in the target lesion. Target lesion within native or synthetic vessel grafts. Subject has more than three target lesions requiring treatment. Subject has significant non-target lesion (>50% stenosis or occlusion) within the target limb (e.g. iliac, common femoral or below-the-knee) not successfully treated prior to treatment of the target lesions. Failure to successfully cross the guidewire across the target lesion; successful crossing defined as tip of the guidewire distal to the target lesion in the absence of flow limiting dissections or perforations.

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: Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL)<br> | Device: Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL)<br>* The Shockwave Medical M5+ Peripheral IVL System is indicated for lithotripsy-enhanced, low-pressure balloon dilatation of lesions, including calcified lesions, in the peripheral vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, and renal arteries. This device is not intended for use in coronary, carotid, or cerebrovascular arteries.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major Adverse Events (MAE) | Defined as: Need for emergency surgical revascularization of target limb Unplanned target limb major amputation (above the ankle) Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization Perforations that require an intervention, including bail-out stenting | 30 days | 
| Number of Lesions With Technical Success | Defined as final residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion by angiographic core lab. | Peri-procedural, approximately 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Lesions With IVL Technical Success | Defined as residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion post-IVL by angiographic core lab | Peri-procedural, approximately 2 hours | 
| Number of Participants With Procedural Success | Defined as final residual stenosis ≤30% without any flow-limiting dissection (≥ Grade D) in all target lesions by angiographic core lab | Peri-procedural, approximately 2 hours | 
| Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography. | 30 days | 
| Rutherford Category Reported as Change From Baseline | Rutherford category at 30 days reported as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene. | 30 days | 
| Number of Participants With Major Adverse Events (MAE) | Need for emergency surgical revascularization of target limb Unplanned target limb major amputation (above the ankle) Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization Perforations that require an intervention, including bail-out stenting | 6 months | 
| Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography. | 6 months | 
| Rutherford Category Reported as Change From Baseline | Rutherford Category at 6 months reported as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene. | 6 months | 
| Number of Participants With Primary Patency | Defined as freedom from clinically-driven target lesion revascularization (TLR) and freedom from restenosis determined by duplex ultrasound or angiogram ≥50% stenosis | 12 months | 
| Number of Participants With Major Adverse Events (MAE) | Need for emergency surgical revascularization of target limb Unplanned target limb major amputation (above the ankle) Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization Perforations that require an intervention, including bail-out stenting | 12 months | 
| Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography. | 12 months | 
| Ankle-brachial Index (ABI) Reported as Change From Baseline | ABI at 12 months reported as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease. | 12 months | 
| Rutherford Category Reported as Change From Baseline | Rutherford Category at 12 months reported as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene. | 12 months |