Shockwave Medical Peripheral Lithoplasty System Study for PAD (Disrupt PAD III)

Randomized Study of the Shockwave Medical Peripheral Lithoplasty® System Used in Combination With DCB Versus Standard Balloon Angioplasty Used in Combination With DCB to Treat Moderate and Severely Calcified Femoropopliteal Arteries

Shockwave Medical Inc. intends to conduct a prospective, multi-center, single blind, randomized (1:1) study of Lithoplasty treatment used in combination with DCB versus standard balloon angioplasty used in combination with DCB to treat moderate and severely calcified femoropopliteal arteries. Assuming that roughly 15% of the subjects will be lost-to-follow-up, a total of up to 400 subjects (200 per treatment arm) will be enrolled in the study at up to 60 sites in Europe, the United States and New Zealand.

In addition to the randomized study, an observational study of subjects who do not meet the inclusion/exclusion criteria for the randomized study will be conducted. The objective of the observational study is to assess the real-world acute performance of the Shockwave Medical Peripheral Lithoplasty System in the treatment of calcified, stenotic, peripheral arteries.

The observational study is a prospective, multi-center, single arm observational study for subjects who do not meet the inclusion/exclusion criteria of the randomized study.

A maximum of 1500 subjects at the same 60 sites will be enrolled in the observational study. Once enrollment in the randomized portion of the study is complete, subjects may continue to be enrolled in the observational study provided they meet OS eligibility criteria.

Results for the observational study will be reported in a separate record under NCT05881421.

Shockwave Medical Inc. intends to conduct a prospective, multi-center, single blind, randomized (1:1) study of Lithoplasty treatment used in combination with DCB versus standard balloon angioplasty used in combination with DCB to treat moderate and severely calcified femoropopliteal arteries. The Shockwave Medical Peripheral Lithoplasty System is indicated for lithotripsy-enhanced, low-pressure balloon dilatation of calcified, stenotic peripheral arteries in patients who are candidates for percutaneous therapy. Up to 400 subjects at 60 sites in Europe, the United States and New Zealand.

Subjects will be followed through discharge, 30 days, and 6, 12 and 24 months. DUS assessments will be completed at 12 and 24 months. Procedural success is defined as residual stenosis ≤30% without flow-limiting dissection (≥ grade D) prior to DCB or stenting by angiographic core lab.

Subjects who do not meet the randomized study inclusion and exclusion criteria, but meet the inclusion and exclusion criteria for the observational study may be enrolled in the observational study. The objective of the observational study is to assess the real-world acute performance of the Shockwave Medical Lithoplasty System in the treatment of calcified, stenotic, peripheral arteries.The observational study is a prospective, multi-center, single arm observational study for subjects who do not meet the inclusion/exclusion criteria of the randomized study. A maximum of 1500 subjects at the same 60 sites will be enrolled in the observational study. Procedural success is defined as residual stenosis ≤30% without flow-limiting dissection (≥ grade D) prior to DCB or stenting by angiographic core lab. Enrollment in the observational study is anticipated to last approximately 22 months. Subjects in the observational study will be followed through hospital discharge. Once enrollment in the randomized portion of the study is complete, subjects may continue to be enrolled in the observational study provided they meet OS eligibility criteria. Results for the observational study will be reported in a separate record under NCT05881421.

Randomized Study Arm Eligibility Criteria

General Inclusion Criteria

1. Subject is able and willing to comply with all assessments in the study.

2. 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.

3. Age of subject is greater than or equal to 18.

4. Rutherford Clinical Category 2, 3, or 4 of the target limb.

5. Estimated life expectancy >1 year.

6. Subject is a suitable candidate for angiography and endovascular intervention in the opinion of the investigator or per hospital guideline.

7. Subject is intended to undergo treatment with Lithoplasty followed by DCB, or DCB with standard balloon pre-dilatation.

   Angiographic Inclusion Criteria

8. Target lesion that is located in a native, de novo superficial femoral artery (SFA) or popliteal artery (popliteal artery extends to and ends proximal to the ostium of the anterior tibial artery).

9. Target lesion reference vessel diameter is between 4.0mm and 7.0mm by visual estimate.

10. Target lesion is ≥70% stenosis by investigator via visual estimate.

11. Target lesion length is ≤180mm for lesions 70-99% stenosed. Target lesion can be all or part of the 180mm treated zone.

12. Chronic total occlusion, lesion length is ≤100mm of the total ≤180 mm target lesion.

13. Subject has at least one patent tibial vessel on the target leg with runoff to the foot, defined as no stenosis >50%.

14. 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

1. Rutherford Clinical Category 0, 1, 5 and 6.

2. Subject has active infection requiring antibiotic therapy.

3. Planned target limb major amputation (above the ankle).

4. History of prior endovascular or surgical procedure on the index limb within the past 30 days or planned within 30 days of the index procedure.

5. Subject has a known coagulopathy or has bleeding diatheses, thrombocytopenia with platelet count less than 100,000/microliter.

6. Subject in whom antiplatelet or anticoagulant therapy is contraindicated.

7. Subject has known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pre-treated.

8. Subject has known allergy to urethane, nylon, or silicone.

9. Myocardial infarction within 60 days prior to enrollment.

10. History of stroke within 60 days prior to enrollment.

11. History of thrombolytic therapy within two weeks of enrollment.

12. Subject has acute or chronic renal disease defined as serum creatinine of >2.5 mg/dL or >220 umol/L, or on dialysis.

13. Subject is pregnant or nursing.

14. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint.

15. 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.

16. The use of specialty balloons, re-entry or atherectomy devices.

    Angiographic Exclusion Criteria

17. In-stent restenosis within 10mm of the target zone.

18. Lesions within 10mm of the ostium of the SFA or within 10mm of the ostium of the anterior tibial artery.

19. Evidence of aneurysm or thrombus in target vessel.

20. No calcium or mild calcium in the target lesion.

21. Target lesion within native or synthetic vessel grafts.

22. Subject has significant stenosis (>50% stenosis) or occlusion of inflow tract before target treatment zone (e.g. iliac or common femoral) not successfully treated.

23. Subject requires treatment of a peripheral lesion on the ipsilateral limb distal to target site at the time of the index procedure.

24. 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.

Subjects who do not meet the inclusion/exclusion criteria for the randomized study may satisfy the eligibility criteria for the observational study.

Observational Study Eligibility Criteria

Inclusion Criteria

1. Subjects intended to be treated with the Shockwave Medical Peripheral Lithoplasty® System for de-novo or restenotic lesions of the femoral, ilio-femoral, popliteal, and infra-popliteal arteries.
2. Subjects presenting with claudication or CLI by Rutherford Clinical Category 2,3,4,5, or 6 of the target limb.
3. Age of subject is > 18.
4. Subject or subject's legal representative have been informed of the nature of the study, agrees to participate, and has signed the approved study consent form.
5. 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.

Exclusion Criteria

1. Subjects with any medical condition that would make him/her an inappropriate candidate for treatment with Shockwave Medical Peripheral Lithoplasty® System as per Instructions for Use (IFU) or investigator's opinion.
2. Subject is already enrolled in other investigational (interventional) studies that would interfere with study endpoints.