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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02923193




Registration number
NCT02923193
Ethics application status
Date submitted
28/09/2016
Date registered
4/10/2016
Date last updated
20/12/2023

Titles & IDs
Public title
Shockwave Medical Peripheral Lithoplasty System Study for PAD (Disrupt PAD III)
Scientific 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
Secondary ID [1] 0 0
CP 60892
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral Arterial Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Shockwave Lithoplasty® Peripheral Lithoplasty System
Treatment: Drugs - Medtronic IN.PACT (DCB)

Experimental: 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

Active comparator: 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.


Treatment: Devices: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Procedural Success
Timepoint [1] 0 0
Peri-Procedural, approximately 2 hours
Secondary outcome [1] 0 0
Number of Participants With Major Adverse Events (MAEs)
Timepoint [1] 0 0
30 days
Secondary outcome [2] 0 0
Clinical Success ABI
Timepoint [2] 0 0
30 days
Secondary outcome [3] 0 0
Clinical Success Quality of Life
Timepoint [3] 0 0
30 days
Secondary outcome [4] 0 0
Clinical Success Rutherford Category
Timepoint [4] 0 0
30 days
Secondary outcome [5] 0 0
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
Timepoint [5] 0 0
30 days
Secondary outcome [6] 0 0
Number of Participants With Major Adverse Events (MAEs)
Timepoint [6] 0 0
6 months
Secondary outcome [7] 0 0
Clinical Success Rutherford Category
Timepoint [7] 0 0
6 months
Secondary outcome [8] 0 0
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
Timepoint [8] 0 0
6 months
Secondary outcome [9] 0 0
Clinical Success ABI
Timepoint [9] 0 0
6 months
Secondary outcome [10] 0 0
Clinical Success Quality of Life
Timepoint [10] 0 0
6 months
Secondary outcome [11] 0 0
Number of Participants With Primary Patency
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Number of Participants With Major Adverse Events (MAEs)
Timepoint [12] 0 0
12 months
Secondary outcome [13] 0 0
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
Timepoint [13] 0 0
12 months
Secondary outcome [14] 0 0
Clinical Success ABI
Timepoint [14] 0 0
12 months
Secondary outcome [15] 0 0
Clinical Success Rutherford Category
Timepoint [15] 0 0
12 months
Secondary outcome [16] 0 0
Clinical Success Quality of Life
Timepoint [16] 0 0
12 months
Secondary outcome [17] 0 0
Number of Participants With Primary Patency
Timepoint [17] 0 0
24 months
Secondary outcome [18] 0 0
Number of Participants With Major Adverse Events (MAEs)
Timepoint [18] 0 0
24 months
Secondary outcome [19] 0 0
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
Timepoint [19] 0 0
24 months
Secondary outcome [20] 0 0
Clinical Success ABI
Timepoint [20] 0 0
24 months
Secondary outcome [21] 0 0
Clinical Success Rutherford Category
Timepoint [21] 0 0
24 months
Secondary outcome [22] 0 0
Clinical Success Quality of Life
Timepoint [22] 0 0
24 months

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/02/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/06/2022
Sample size
Target
Accrual to date
Final
306
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
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United States of America
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Maine
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United States of America
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Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
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Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Rhode Island
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
West Virginia
Country [25] 0 0
Austria
State/province [25] 0 0
Graz
Country [26] 0 0
Austria
State/province [26] 0 0
Vienna
Country [27] 0 0
Germany
State/province [27] 0 0
Arnsberg
Country [28] 0 0
Germany
State/province [28] 0 0
Bad Krozingen
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Bonn
Country [31] 0 0
Germany
State/province [31] 0 0
Bruchsal
Country [32] 0 0
Germany
State/province [32] 0 0
Hamburg
Country [33] 0 0
Germany
State/province [33] 0 0
Leipzig
Country [34] 0 0
Germany
State/province [34] 0 0
Mainz
Country [35] 0 0
Germany
State/province [35] 0 0
Munster
Country [36] 0 0
Germany
State/province [36] 0 0
Mülheim
Country [37] 0 0
Germany
State/province [37] 0 0
Rosenheim
Country [38] 0 0
New Zealand
State/province [38] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Shockwave Medical, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02923193
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Gunnar Tepe, MD
Address 0 0
RoMed Klinikum Rosenheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02923193