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

Peripheral Arterial Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02923193
• Other study ID #: CP 60892
• Status: Completed
• Phase: N/A
• Start date: February 22, 2017
• Est. completion date: June 2, 2022

Study information

• Verified date: December 2023
• Source: Shockwave Medical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: June 2, 2022
• Est. primary completion date: May 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Device:
• 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.

Drug:
• 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.

Locations

Country	Name	City	State
Austria	Medizinische Universitaet Graz	Graz
Austria	Gefäßsambulanz	Vienna
Germany	Karolinen-Hospital	Arnsberg
Germany	Universitäts-Herzzentrum Freiburg & Bad Krozingen	Bad Krozingen
Germany	Sankt Gertrauden-Krankenhaus	Berlin
Germany	Leiter Sektion Angiologie	Bonn
Germany	Medizinische Klinik II	Bruchsal
Germany	Klinik für Gefäßmedizin	Hamburg
Germany	Universitätsklinikum Leipzig AoR Leipzig	Leipzig
Germany	Katholisches Klinikum Mainz	Mainz
Germany	Evangelisches Krankenhaus Mühlheim an der Ruhr	Mülheim
Germany	St. Franziskus Hospital	Munster
Germany	RoMed Klinikum Rosenheim	Rosenheim
New Zealand	Auckland City Hospital	Auckland
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	Rocky Mountain Regional VA Medical Center	Aurora	Colorado
United States	St. David's Heart and Vascular dba Austin Heart	Austin	Texas
United States	St. John Clinic	Bartlesville	Oklahoma
United States	Steward St. Elizabeth's Medical Center	Brighton	Maine
United States	Deborah Heart and Lung Center	Browns Mills	New Jersey
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	Ohio Health Research Institute	Columbus	Ohio
United States	Midwest Cardiovascular Research Foundation	Davenport	Iowa
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	PinnacleHealth Harrisburg Hospital	Harrisburg	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Saint Luke's Cardiovascular Consultants	Kansas City	Missouri
United States	Wellmont CVA Heart Institute	Kingsport	Tennessee
United States	Tennova Healthcare - Turkey Creek Medical Center	Knoxville	Tennessee
United States	St. Luke's East Hospital	Lee's Summit	Missouri
United States	Arkansas Heart Hospital	Little Rock	Arkansas
United States	UCHealth Northern Colorado	Loveland	Colorado
United States	Baptist Medical Center	Memphis	Tennessee
United States	Advocate Health and Hospitals Corporation	Naperville	Illinois
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Columbia University Medical Center/New York Presbyterian Hospital	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mount Sinai West	New York	New York
United States	Stanford Hospital	Palo Alto	California
United States	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Providence Heart & Vascular Institute	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	The Miriam Hospital	Providence	Rhode Island
United States	NC Heart & Vascular Research	Raleigh	North Carolina
United States	WakeMed Health & Hospitals	Raleigh	North Carolina
United States	Ascension / St. John Providence	Southfield	Michigan
United States	Prairie Education & Research Cooperative	Springfield	Illinois
United States	Tallahassee Research Institute, Inc.	Tallahassee	Florida
United States	North Mississippi Medical Center	Tupelo	Mississippi
United States	MedStar Cardiovascular Research Network @ Medstar Washington Hospital Center	Washington	District of Columbia
United States	Lankenau Institute for Medical Research	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Shockwave Medical, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Germany,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Procedural Success	Procedural success is defined as residual stenosis =30% without flow-limiting dissection (= grade D) prior to DCB or stenting by angiographic core lab.	Peri-Procedural, approximately 2 hours
Secondary	Number of Participants With 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	30 days
Secondary	Clinical Success ABI	Defined as ankle-brachial index ABI reported at 30 days as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease.	30 days
Secondary	Clinical Success Quality of Life	Defined by Quality of Life assessed by EQ5D questionnaire reported at 30 days as change from baseline. The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The overall summary index (from Shaw et. al.) computed from the 5-dimension sub-scores was applied. It ranges from 0.000 to 1.000; higher scores indicate better patient-reported health status."	30 days
Secondary	Clinical Success Rutherford Category	Defined as Rutherford Category reported at 30 days as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene.	30 days
Secondary	Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)	Any revascularization (endovascular or surgical) within the target femoropopliteal vessel due to symptoms or drop of ABI >20% or >0.15 when compared to the 30-day ABI and associated with an angiographic lesion >50% at the target lesion site	30 days
Secondary	Number of Participants With 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	6 months
Secondary	Clinical Success Rutherford Category	Defined as Rutherford Category reported at 6 months as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene.	6 months
Secondary	Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)	Any revascularization (endovascular or surgical) within the target femoropopliteal vessel due to symptoms or drop of ABI >20% or >0.15 when compared to the 30-day ABI and associated with an angiographic lesion >50% at the target lesion site	6 months
Secondary	Clinical Success ABI	Defined as ankle-brachial index ABI reported at 6 months as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease.	6 months
Secondary	Clinical Success Quality of Life	Defined by Quality of Life assessed by EQ5D questionnaire reported at 6 months as change from baseline. The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The overall summary index (from Shaw et. al.) computed from the 5-dimension sub-scores was applied and ranges from 0.000 to 1.000; higher scores indicate better patient-reported health status.	6 months
Secondary	Number of Participants With 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.	12 months
Secondary	Number of Participants With 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	12 months
Secondary	Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)	Any revascularization (endovascular or surgical) within the target femoropopliteal vessel due to symptoms or drop of ABI >20% or >0.15 when compared to the 30-day ABI and associated with an angiographic lesion >50% at the target lesion site	12 months
Secondary	Clinical Success ABI	Defined as ankle-brachial index ABI reported at 12 months as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease.	12 months
Secondary	Clinical Success Rutherford Category	Defined as Rutherford Category reported at 12 months as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene.	12 months
Secondary	Clinical Success Quality of Life	Defined by Quality of Life assessed by EQ5D questionnaire reported at 12 months as change from baseline. The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The overall summary index (from Shaw et. al.) computed from the 5-dimension sub-scores was applied and ranges from 0.000 to 1.000; higher scores indicate better patient-reported health status.	12 months
Secondary	Number of Participants With 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.	24 months
Secondary	Number of Participants With 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	24 months
Secondary	Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)	Any revascularization (endovascular or surgical) within the target femoropopliteal vessel due to symptoms or drop of ABI >20% or >0.15 when compared to the 30-day ABI and associated with an angiographic lesion >50% at the target lesion site	24 months
Secondary	Clinical Success ABI	Defined as ankle-brachial index ABI reported at 24 months as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease.	24 months
Secondary	Clinical Success Rutherford Category	Defined as Rutherford Category reported at 24 months as change from baseline. Clinical scale identifying three grades of claudication and three grades of critical limb ischemia ranging from rest pain alone to minor and major tissue loss. 0 is asymptomatic and 6 is ulcers/gangrene.	24 months
Secondary	Clinical Success Quality of Life	Defined by Quality of Life assessed by EQ5D questionnaire reported at 24 months as change from baseline. The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The overall summary index (from Shaw et. al.) computed from the 5-dimension sub-scores was applied and ranges from 0.000 to 1.000; higher scores indicate better patient-reported health status.	24 months

External Links

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