Disrupt CAD III With the Shockwave Coronary IVL System

NCT ID: NCT03595176

Last Updated: 2023-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 431 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-09
• Study Completion Date: 2022-04-10

Brief Summary

The study design is a prospective, multicenter, single-arm, global IDE study to evaluate the safety and effectiveness of the Shockwave Medical Coronary Intravascular Lithotripsy (IVL) System in de novo, calcified, stenotic coronary arteries prior to stenting. Disrupt CAD III is being conducted as a staged pivotal study.

Detailed Description

Subject Population: Subjects ≥ 18 years of age with de novo, calcified coronary artery lesions presenting with stable, unstable or silent ischemia that are suitable for percutaneous coronary intervention (PCI). Approximately 392 subjects at 50 sites will be enrolled. A minimum of 50% of the total enrollment will come from the United States.Subjects will be followed through discharge, 30 days, 6, 12 and 24 months.

Conditions

Coronary Artery Disease; Myocardial Infarction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Coronary Lithotripsy System

All subjects will receive lithotripsy treatment from the Shockwave Medical Coronary IVL System

Group Type: EXPERIMENTAL

Lithotripsy

Intervention Type: DEVICE

Deliver Lithotripsy to the target vessel prior to placing a coronary stent.

Interventions

Lithotripsy

Deliver Lithotripsy to the target vessel prior to placing a coronary stent.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Subject is ≥18 years of age

2. Subjects with native coronary artery disease (including stable or unstable angina and silent ischemia) suitable for PCI

3. For patients with unstable ischemic heart disease, biomarkers (troponin or CK-MB) must be less than or equal to the upper limit of lab normal within 12 hours prior to the procedure (note: if both labs are drawn, both must be normal).

4. For patients with stable ischemic heart disease, biomarkers may be drawn prior to the procedure or at the time of the procedure from the side port of the sheath.

1. If drawn prior to the procedure, biomarkers (troponin or CK-MB) must be less than or equal to the upper limit of lab normal within 12 hours of the procedure (note: if both labs are drawn, both must be normal).

2. If biomarkers are drawn at the time of the procedure from the side port of the sheath prior to any intervention, biomarker results do not need to be analyzed prior to enrollment (note: CK-MB is required if drawn from the sheath).

5. Left ventricular ejection fraction >25% within 6 months (note: in the case of multiple assessments of LVEF, the measurement closest to enrollment will be used for this criteria; may be assessed at time of index procedure)

6. Subject or legally authorized representative, signs a written Informed Consent form to participate in the study, prior to any study-mandated procedures

7. Lesions in non-target vessels requiring PCI may be treated either:

1. >30 days prior to the study procedure if the procedure was unsuccessful or complicated; or

2. >24 hours prior to the study procedure if the procedure was successful and uncomplicated (defined as a final lesion angiographic diameter stenosis <30% and TIMI 3 flow (visually assessed) for all non-target lesions and vessels without perforation, cardiac arrest or need for defibrillation or cardioversion or hypotension/heart failure requiring mechanical or intravenous hemodynamic support or intubation, and with no post-procedure biomarker elevation >normal; or

3. >30 days after the study procedure

8. The target lesion must be a de novo coronary lesion that has not been previously treated with any interventional procedure

9. Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX (or of their branches) with:

1. Stenosis of ≥70% and <100% or

2. Stenosis ≥50% and <70% (visually assessed) with evidence of ischemia via positive stress test, or fractional flow reserve value ≤0.80, or iFR <0.90 or IVUS or OCT minimum lumen area ≤4.0 mm²

10. The target vessel reference diameter must be ≥2.5 mm and ≤4.0 mm

11. The lesion length must not exceed 40 mm

12. The target vessel must have TIMI flow 3 at baseline (visually assessed; may be assessed after pre- dilatation)

13. Evidence of calcification at the lesion site by, a) angiography, with fluoroscopic radio-opacities noted without cardiac motion prior to contrast injection involving both sides of the arterial wall in at least one location and total length of calcium of at least 15 mm and extending partially into the target lesion, OR by b) IVUS or OCT, with presence of ≥270 degrees of calcium on at least 1 cross section

14. Ability to pass a 0.014" guide wire across the lesion

Exclusion Criteria

1. Any comorbidity or condition which may reduce compliance with this protocol, including follow-up visits

2. Subject is a member of a vulnerable population as defined in 21 CFR 56.111, including individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention

3. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint

4. Subject is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrollment)

5. Unable to tolerate dual antiplatelet therapy (i.e., aspirin, and either clopidogrel, prasugrel, or ticagrelor) for at least 6 months (for patients not on oral anticoagulation)

6. Subject has an allergy to imaging contrast media which cannot be adequately pre-medicated

7. Subject experienced an acute MI (STEMI or non-STEMI) within 30 days prior to index procedure, defined as a clinical syndrome consistent with an acute coronary syndrome with troponin or CK-MB greater than 1 times the local laboratory's upper limit of normal

8. New York Heart Association (NYHA) class III or IV heart failure

9. Renal failure with serum creatinine >2.5 mg/dL or chronic dialysis

10. History of a stroke or transient ischemic attack (TIA) within 6 months, or any prior intracranial hemorrhage or permanent neurologic deficit

11. Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months

12. Untreated pre-procedural hemoglobin <10 g/dL or intention to refuse blood transfusions if one should become necessary

13. Coagulopathy, including but not limited to platelet count <100,000 or International Normalized ratio (INR) > 1.7 (INR is only required in subjects who have taken warfarin within 2 weeks of enrollment)

14. Subject has a hypercoagulable disorder such as polycythemia vera, platelet count >750,000 or other disorders

15. Uncontrolled diabetes defined as a HbA1c greater than or equal to 10%

16. Subject has an active systemic infection on the day of the index procedure with either fever, leukocytosis or requiring intravenous antibiotics

17. Subjects in cardiogenic shock or with clinical evidence of left-sided heart failure (S3 gallop, pulmonary rales, oliguria, or hypoxemia)

18. Uncontrolled severe hypertension (systolic BP >180 mm Hg or diastolic BP >110 mm Hg)

19. Subjects with a life expectancy of less than 1 year

20. Non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion, etc.) within 30 days prior to the index procedure

21. Planned non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion, etc.) within 30 days after the index procedure

22. Subject refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery

23. Planned use of atherectomy, scoring or cutting balloon, or any investigational device other than lithotripsy

24. High SYNTAX Score (≥33) if assessed as standard of care, unless the local heart team has met and recommends PCI is the most appropriate treatment for the patient

25. Unprotected left main diameter stenosis >30%

26. Target vessel is excessively tortuous defined as the presence of two or more bends >90º or three or more bends >75º

27. Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel

28. Evidence of aneurysm in target vessel within 10 mm of the target lesion

29. Target lesion is an ostial location (LAD, LCX, or RCA, within 5 mm of ostium) or an unprotected left main lesion

30. Target lesion is a bifurcation with ostial diameter stenosis ≥30%

31. Second lesion with >50% stenosis in the same target vessel as the target lesion including its side branches

32. Target lesion is located in a native vessel that can only be reached by going through a saphenous vein or arterial bypass graft

33. Previous stent within the target vessel implanted within the last year

34. Previous stent within 10 mm of the target lesion regardless of the timing of its implantation

35. Angiographic evidence of a dissection in the target vessel at baseline or after guidewire passage

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shockwave Medical, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dean J Kereiakes, MD,FACC,FSCAI

Role: STUDY_CHAIR

The Christ Hospital Heart and Vascular Center and The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital

Gregg W Stone, MD,FACC,FSCAI

Role: STUDY_CHAIR

Columbia University

Jonathan Hill, MD

Role: STUDY_CHAIR

Royal Brompton and Harefield NHS Foundation Trust

Locations

Honor Health

Scottsdale, Arizona, United States

Scripps Clinic

La Jolla, California, United States

University of California, San Diego (UCSD) - Medical Center

La Jolla, California, United States

St. Joseph Hospital

Orange, California, United States

VA Palo Alto Health Care System

Palo Alto, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

MedStar Washington Hospital Center

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

Emory University Hospital Midtown

Atlanta, Georgia, United States

Piedmont Heart Institute

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Advocate Health and Hospitals Corporation - Edward Hospital

Oakbrook Terrace, Illinois, United States

St. Vincent Heart Center of Indiana, LLC

Indianapolis, Indiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

MedStar Union Memorial Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

North Mississippi Medical Center

Tupelo, Mississippi, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Deborah Heart and Lung Center

Browns Mills, New Jersey, United States

New York University (NYU) Langone Medical Center

New York, New York, United States

Columbia University Medical Center/ New York Presbyterian

New York, New York, United States

St. Francis Hospital

Roslyn, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Durham VA Health Care System

Durham, North Carolina, United States

NC Heart and Vascular

Raleigh, North Carolina, United States

The Christ Hospital

Cincinnati, Ohio, United States

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Pinnacle Health Cardiovascular Institute Inc.

Wormleysburg, Pennsylvania, United States

The Miriam Hospital

Providence, Rhode Island, United States

Baylor Heart and Vascular Hospital

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Vermont

Burlington, Vermont, United States

University of Washington Medical Center

Seattle, Washington, United States

Charleston Area Medical Center (CAMC) - Health Education & Research Institute

Charleston, West Virginia, United States

Clinique Pasteur

Toulouse, Cedex 3, France

Clinique des Domes - Pole Sante Republique

Clermont-Ferrand, , France

Institute Cardiovasculaire Paris Sud

Massy, , France

Universitaetsklinikum Giessen and Marburg GmbH

Marburg, CET, Germany

Charité - Universitaetsmedizin Berlin

Berlin, , Germany

Rheinland Klinikum Neuss GmbH - Lukaskrankenhaus Neuss

Neuss, , Germany

Golden Jubilee National Hospital

Clydebank, , United Kingdom

St. Bartholomew's Hospital

London, , United Kingdom

King's College Hospital

London, , United Kingdom

Countries

United States; France; Germany; United Kingdom

References

Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, Riley RF, Price MJ, Herrmann HC, Bachinsky W, Waksman R, Stone GW; Disrupt CAD III Investigators. Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease. J Am Coll Cardiol. 2020 Dec 1;76(22):2635-2646. doi: 10.1016/j.jacc.2020.09.603. Epub 2020 Oct 15.

Reference Type: RESULT

PMID: 33069849 (View on PubMed)

Kereiakes DJ, Hill JM, Ben-Yehuda O, Maehara A, Alexander B, Stone GW. Evaluation of safety and efficacy of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: Design and rationale for the Disrupt CAD III trial. Am Heart J. 2020 Jul;225:10-18. doi: 10.1016/j.ahj.2020.04.005. Epub 2020 Apr 18.

Reference Type: RESULT

PMID: 32470635 (View on PubMed)

Kereiakes DJ, Di Mario C, Riley RF, Fajadet J, Shlofmitz RA, Saito S, Ali ZA, Klein AJ, Price MJ, Hill JM, Stone GW. Intravascular Lithotripsy for Treatment of Calcified Coronary Lesions: Patient-Level Pooled Analysis of the Disrupt CAD Studies. JACC Cardiovasc Interv. 2021 Jun 28;14(12):1337-1348. doi: 10.1016/j.jcin.2021.04.015. Epub 2021 May 3.

Reference Type: DERIVED

PMID: 33939604 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://doi.org/10.1016/j.jscai.2021.100001

Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Lesions: 1-Year Results From the Disrupt CAD III Study

Other Identifiers

CP 61982

Identifier Type: -

Identifier Source: org_study_id