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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02923193
Ethics application status
Date submitted
28/09/2016
Date registered
4/10/2016
Date last updated
28/08/2019

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 FreePacâ„¢ 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
Procedural success is defined as residual stenosis =30% without flow-limiting dissection (= grade D) prior to DCB or stenting by angiographic core lab. - Procedural success is defined as residual stenosis =30% without flow-limiting dissection (= grade D) prior to DCB or stenting by angiographic core lab.
Timepoint [1] 0 0
Peri-Procedural
Secondary outcome [1] 0 0
Primary patency defined as freedom from clinically-driven target lesion revascularization (TLR) and freedom from restenosis determined by duplex ultrasound or angiogram greater than or equal to 50% stenosis. - Acute PTA failure requiring a stent at any time during the index procedure will be counted as a loss of primary patency.
Timepoint [1] 0 0
Peri-Procedural
Secondary outcome [2] 0 0
Composite of new-onset Major Adverse Events (MAEs) - Need for emergency surgical revascularization of target limb
Unplanned target limb major amputation (above the ankle)
Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization
Perforations that require an intervention, including bail-out stenting
Timepoint [2] 0 0
Within 30 days, 6, 12 and 24 months post procedure
Secondary outcome [3] 0 0
Primary patency - Defined as freedom from clinically-driven target lesion revascularization (TLR)
Timepoint [3] 0 0
30 days, 6, 12 and 24 months
Secondary outcome [4] 0 0
Clinical Success ABI - Defined as ankle-brachial index ABI reported as change from baseline
Timepoint [4] 0 0
30 days, 6, 12 and 24 months
Secondary outcome [5] 0 0
Clinical Success Rutherford Category - Defined as Rutherford Category reported as change from baseline
Timepoint [5] 0 0
30 days, 6, 12 and 24 months
Secondary outcome [6] 0 0
Clinical Success Quality of Life - Defined by Quality of Life assessed by EQ5D questionnaire reported as change from baseline
Timepoint [6] 0 0
30 days, 6, 12 and 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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Connecticut
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District of Columbia
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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Tennessee
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Texas
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West Virginia
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Austria
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Graz
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Austria
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Vienna
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Germany
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Arnsberg
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Germany
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Bad Krozingen
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Berlin
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Germany
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Bonn
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Bruchsal
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Hamburg
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Leipzig
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Mainz
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Munster
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Germany
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Mülheim
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Germany
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Rosenheim
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New Zealand
State/province [41] 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 1000 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.
Trial website
https://clinicaltrials.gov/show/NCT02923193
Trial related presentations / publications
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
Alexis Brash
Address 0 0
Country 0 0
Phone 0 0
1-510-624-9093
Fax 0 0
Email 0 0
abrash@shockwavemedical.com
Contact person for scientific queries

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