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

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 1000 subjects at the same 60 sites will be enrolled in the
observational study. Procedural success defined as residual stenosis <30% prior to DCB or
stenting by angiographic core lab. Enrollment in the observational study is anticipated to
last approximately 16 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.

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.