Clinical trial NCT02923193: Shockwave Medical Peripheral Lithoplasty System Study for PAD (Disrupt PAD III)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Arterial Disease
Lead sponsor: Shockwave Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-04
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

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.

Primary outcomes:
measure: Number of Participants With Procedural Success
timeFrame: Peri-Procedural, approximately 2 hours
Secondary outcomes:
measure: Number of Participants With Major Adverse Events (MAEs)
timeFrame: 30 days
measure: Clinical Success ABI
timeFrame: 30 days
measure: Clinical Success Quality of Life
timeFrame: 30 days
measure: Clinical Success Rutherford Category
timeFrame: 30 days
measure: Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
timeFrame: 30 days
measure: Number of Participants With Major Adverse Events (MAEs)
timeFrame: 6 months
measure: Clinical Success Rutherford Category
timeFrame: 6 months
measure: Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
timeFrame: 6 months
measure: Clinical Success ABI
timeFrame: 6 months
measure: Clinical Success Quality of Life
timeFrame: 6 months
measure: Number of Participants With Primary Patency
timeFrame: 12 months
measure: Number of Participants With Major Adverse Events (MAEs)
timeFrame: 12 months
measure: Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
timeFrame: 12 months
measure: Clinical Success ABI
timeFrame: 12 months
measure: Clinical Success Rutherford Category
timeFrame: 12 months
measure: Clinical Success Quality of Life
timeFrame: 12 months
measure: Number of Participants With Primary Patency
timeFrame: 24 months
measure: Number of Participants With Major Adverse Events (MAEs)
timeFrame: 24 months
measure: Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
timeFrame: 24 months
measure: Clinical Success ABI
timeFrame: 24 months
measure: Clinical Success Rutherford Category
timeFrame: 24 months
measure: Clinical Success Quality of Life
timeFrame: 24 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford Hospital
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center
state: Colorado
city: Loveland
country: United States
facility: UCHealth Northern Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Cardiovascular Research Network @ Medstar Washington Hospital Center
state: District of Columbia
city: Tallahassee
country: United States
facility: Tallahassee Research Institute, Inc.
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical Center
state: Illinois
city: Naperville
country: United States
facility: Advocate Health and Hospitals Corporation
state: Illinois
city: Springfield
country: United States
facility: Prairie Education & Research Cooperative
state: Illinois
city: Davenport
country: United States
facility: Midwest Cardiovascular Research Foundation
state: Iowa
city: Brighton
country: United States
facility: Steward St. Elizabeth's Medical Center
state: Maine
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Southfield
country: United States
facility: Ascension / St. John Providence
state: Michigan
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Cardiovascular Consultants
state: Missouri
city: Lee's Summit
country: United States
facility: St. Luke's East Hospital
state: Missouri
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/New York Presbyterian Hospital
state: New York
city: Raleigh
country: United States
facility: NC Heart & Vascular Research
state: North Carolina
city: Raleigh
country: United States
facility: WakeMed Health & Hospitals
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Bartlesville
country: United States
facility: St. John Clinic
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Heart & Vascular Institute
state: Oregon
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Harrisburg
country: United States
facility: PinnacleHealth Harrisburg Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Medical Center Philadelphia
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Institute for Medical Research
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Kingsport
country: United States
facility: Wellmont CVA Heart Institute
state: Tennessee
city: Knoxville
country: United States
facility: Tennova Healthcare - Turkey Creek Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Baptist Medical Center
state: Tennessee
city: Austin
country: United States
facility: St. David's Heart and Vascular dba Austin Heart
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Vienna
country: Austria
facility: Gefäßsambulanz
city: Arnsberg
country: Germany
facility: Karolinen-Hospital
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg & Bad Krozingen
city: Berlin
country: Germany
facility: Sankt Gertrauden-Krankenhaus
city: Bonn
country: Germany
facility: Leiter Sektion Angiologie
city: Bruchsal
country: Germany
facility: Medizinische Klinik II
city: Hamburg
country: Germany
facility: Klinik für Gefäßmedizin
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AoR Leipzig
city: Mainz
country: Germany
facility: Katholisches Klinikum Mainz
city: Munster
country: Germany
facility: St. Franziskus Hospital
city: Mülheim
country: Germany
facility: Evangelisches Krankenhaus Mühlheim an der Ruhr
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: RoMed Klinikum Rosenheim
name: Gunnar Tepe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Main Line Health
name: William A Gray, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tepe G, Brodmann M, Werner M, Bachinsky W, Holden A, Zeller T, Mangalmurti S, Nolte-Ernsting C, Bertolet B, Scheinert D, Gray WA; Disrupt PAD III Investigators. Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Randomized Disrupt PAD III Trial. JACC Cardiovasc Interv. 2021 Jun 28;14(12):1352-1361. doi: 10.1016/j.jcin.2021.04.010.
citation: Adams G, Shammas N, Mangalmurti S, Bernardo NL, Miller WE, Soukas PA, Parikh SA, Armstrong EJ, Tepe G, Lansky A, Gray WA. Intravascular Lithotripsy for Treatment of Calcified Lower Extremity Arterial Stenosis: Initial Analysis of the Disrupt PAD III Study. J Endovasc Ther. 2020 Jun;27(3):473-480. doi: 10.1177/1526602820914598. Epub 2020 Apr 3.