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

NCT ID: NCT02923193

Last Updated: 2023-12-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

306 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-22

Study Completion Date

2022-06-02

Brief Summary

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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

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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.

Conditions

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Peripheral Arterial Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Lithoplasty System followed by DCB

Shockwave Lithoplasty® Peripheral Lithoplasty System is a lithotripsy-enhanced, low-pressure balloon dilatation of calcified, stenotic peripheral arteries in patients who are candidates for percutaneous therapy. lithoplasty

Group Type EXPERIMENTAL

Shockwave Lithoplasty® Peripheral Lithoplasty System

Intervention Type DEVICE

The Shockwave Lithoplasty® System is a proprietary lithotripsy-enhanced balloon catheter that is designed to be delivered through the peripheral arterial system of the lower extremities to the site of calcified stenosis. Activating the lithotripsy within the device will generate pulsatile mechanical energy within the target treatment site, disrupt calcium within the lesion and allow subsequent dilation of a peripheral artery stenosis using low balloon pressure. The system consists of a balloon catheter with multiple integrated lithotripsy electrodes, and a generator.

Medtronic IN.PACT (DCB)

Intervention Type DRUG

The IN.PACT Admiral DCB is an over-the-wire (OTW) balloon catheter with a drug-coated balloon at the distal tip. The drug component, referred to as the FreePac™ drug coating, consists of the drug paclitaxel and the excipient urea. The device component physically dilates the vessel lumen by PTA, and the drug is intended to reduce the proliferative response that is associated with restenosis.

Medtronic IN.PACT (DCB)

Medronic IN.PACT Drug Coated Balloon (DBS) is indicated for percutaneous transluminal angioplasty (PTA) in patients with obstructive disease of peripheral arteries, including patients with in-stent restenosis (ISR) and arteriovenous (AV) access to help maintain hemodialysis access in patients with end-stage renal disease.

Group Type ACTIVE_COMPARATOR

Medtronic IN.PACT (DCB)

Intervention Type DRUG

The IN.PACT Admiral DCB is an over-the-wire (OTW) balloon catheter with a drug-coated balloon at the distal tip. The drug component, referred to as the FreePac™ drug coating, consists of the drug paclitaxel and the excipient urea. The device component physically dilates the vessel lumen by PTA, and the drug is intended to reduce the proliferative response that is associated with restenosis.

Interventions

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Shockwave Lithoplasty® Peripheral Lithoplasty System

The Shockwave Lithoplasty® System is a proprietary lithotripsy-enhanced balloon catheter that is designed to be delivered through the peripheral arterial system of the lower extremities to the site of calcified stenosis. Activating the lithotripsy within the device will generate pulsatile mechanical energy within the target treatment site, disrupt calcium within the lesion and allow subsequent dilation of a peripheral artery stenosis using low balloon pressure. The system consists of a balloon catheter with multiple integrated lithotripsy electrodes, and a generator.

Intervention Type DEVICE

Medtronic IN.PACT (DCB)

The IN.PACT Admiral DCB is an over-the-wire (OTW) balloon catheter with a drug-coated balloon at the distal tip. The drug component, referred to as the FreePac™ drug coating, consists of the drug paclitaxel and the excipient urea. The device component physically dilates the vessel lumen by PTA, and the drug is intended to reduce the proliferative response that is associated with restenosis.

Intervention Type DRUG

Other Intervention Names

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drug coated balloon

Eligibility Criteria

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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.

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.


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. 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.

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.


Observational Study Eligibility 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shockwave Medical, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gunnar Tepe, MD

Role: PRINCIPAL_INVESTIGATOR

RoMed Klinikum Rosenheim

William A Gray, MD

Role: PRINCIPAL_INVESTIGATOR

Main Line Health

Locations

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Arkansas Heart Hospital

Little Rock, Arkansas, United States

Site Status

Stanford Hospital

Palo Alto, California, United States

Site Status

Rocky Mountain Regional VA Medical Center

Aurora, Colorado, United States

Site Status

UCHealth Northern Colorado

Loveland, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

MedStar Cardiovascular Research Network @ Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Tallahassee Research Institute, Inc.

Tallahassee, Florida, United States

Site Status

Piedmont Heart Institute

Atlanta, Georgia, United States

Site Status

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Site Status

Alexian Brothers Medical Center

Elk Grove Village, Illinois, United States

Site Status

Advocate Health and Hospitals Corporation

Naperville, Illinois, United States

Site Status

Prairie Education & Research Cooperative

Springfield, Illinois, United States

Site Status

Midwest Cardiovascular Research Foundation

Davenport, Iowa, United States

Site Status

Steward St. Elizabeth's Medical Center

Brighton, Maine, United States

Site Status

St. Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Ascension / St. John Providence

Southfield, Michigan, United States

Site Status

North Mississippi Medical Center

Tupelo, Mississippi, United States

Site Status

Saint Luke's Cardiovascular Consultants

Kansas City, Missouri, United States

Site Status

St. Luke's East Hospital

Lee's Summit, Missouri, United States

Site Status

Deborah Heart and Lung Center

Browns Mills, New Jersey, United States

Site Status

Mount Sinai West

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Columbia University Medical Center/New York Presbyterian Hospital

New York, New York, United States

Site Status

NC Heart & Vascular Research

Raleigh, North Carolina, United States

Site Status

WakeMed Health & Hospitals

Raleigh, North Carolina, United States

Site Status

Ohio Health Research Institute

Columbus, Ohio, United States

Site Status

St. John Clinic

Bartlesville, Oklahoma, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Providence Heart & Vascular Institute

Portland, Oregon, United States

Site Status

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Site Status

PinnacleHealth Harrisburg Hospital

Harrisburg, Pennsylvania, United States

Site Status

Einstein Medical Center Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Lankenau Institute for Medical Research

Wynnewood, Pennsylvania, United States

Site Status

The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Wellmont CVA Heart Institute

Kingsport, Tennessee, United States

Site Status

Tennova Healthcare - Turkey Creek Medical Center

Knoxville, Tennessee, United States

Site Status

Baptist Medical Center

Memphis, Tennessee, United States

Site Status

St. David's Heart and Vascular dba Austin Heart

Austin, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Charleston Area Medical Center

Charleston, West Virginia, United States

Site Status

Medizinische Universitaet Graz

Graz, , Austria

Site Status

Gefäßsambulanz

Vienna, , Austria

Site Status

Karolinen-Hospital

Arnsberg, , Germany

Site Status

Universitäts-Herzzentrum Freiburg & Bad Krozingen

Bad Krozingen, , Germany

Site Status

Sankt Gertrauden-Krankenhaus

Berlin, , Germany

Site Status

Leiter Sektion Angiologie

Bonn, , Germany

Site Status

Medizinische Klinik II

Bruchsal, , Germany

Site Status

Klinik für Gefäßmedizin

Hamburg, , Germany

Site Status

Universitätsklinikum Leipzig AoR Leipzig

Leipzig, , Germany

Site Status

Katholisches Klinikum Mainz

Mainz, , Germany

Site Status

Evangelisches Krankenhaus Mühlheim an der Ruhr

Mülheim, , Germany

Site Status

St. Franziskus Hospital

Münster, , Germany

Site Status

RoMed Klinikum Rosenheim

Rosenheim, , Germany

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Countries

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United States Austria Germany New Zealand

References

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Nagpal S, Altin SE, McGinigle K, Mangalmurti SS, Adams G, Shammas NW, Mehrle A, Soukas P, Bertolet B, Lansky AJ. Sex-specific analysis of intravascular lithotripsy for peripheral artery disease from the Disrupt PAD III observational study. J Vasc Surg. 2024 Feb;79(2):358-365. doi: 10.1016/j.jvs.2023.10.058. Epub 2023 Nov 2.

Reference Type DERIVED
PMID: 37925039 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34167675 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32242768 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://pubmed.ncbi.nlm.nih.gov/32147133/

Intravascular lithotripsy for treatment of calcified, stenotic iliac arteries: A cohort analysis from the Disrupt PAD III Study

Other Identifiers

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CP 60892

Identifier Type: -

Identifier Source: org_study_id