Clinical trial NCT03595176: Disrupt CAD III With the Shockwave Coronary IVL System
Official title: Prospective, Multicenter, Single-Arm, Global IDE Study of the Shockwave Coronary Intravascular Lithotripsy (IVL) System With the Shockwave C2 Coronary IVL Catheter in Calcified Coronary Arteries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Myocardial Infarction
Keywords: Intravascular Lithotripsy
Percutaneous Coronary Intervention
Lead sponsor: Shockwave Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 431
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The Coronary IVL System is a proprietary balloon catheter system designed to enhance stent outcomes by enabling delivery of the calcium disrupting capability of lithotripsy prior to balloon dilatation at low pressures. The Coronary IVL System consists of an IVL Balloon Catheter with two integrated pairs of lithotripsy emitters, a Lithotripsy Generator, and Connector Cable.
Primary purpose: TREATMENT

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.

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

   Angiographic Inclusion Criteria
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

Primary outcomes:
measure: Number of Participants Who Experienced Freedom From Major Adverse Cardiac Events (MACE) Within 30 Days Post-procedure
timeFrame: within 30 days of index procedure
measure: Number of Participants With Procedural Success (Residual Stenosis <50%)
timeFrame: 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure
Secondary outcomes:
measure: Number of Participants With Device Crossing Success
timeFrame: at end of procedure
measure: Number of Participants With Angiographic Success (Residual Stenosis <50%)
timeFrame: at end of procedure
measure: Number of Participants With Procedural Success (Residual Stenosis <=30%)
timeFrame: 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure
measure: Number of Participants With Angiographic Success (Residual Stenosis <=30%)
timeFrame: at end of procedure
measure: Number of Participants With Serious Angiographic Complications
timeFrame: at end of procedure
measure: MACE Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: MACE Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: MACE Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Target Lesion Failure (TLF) Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Target Lesion Failure (TLF) Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Target Lesion Failure (TLF) Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Target Lesion Failure (TLF) Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: All-Cause Death Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: All-Cause Death Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: All-Cause Death Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: All-Cause Death Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Cardiac Death Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Cardiac Death Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Cardiac Death Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Cardiac Death Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: MI Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: MI Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: MI Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: MI Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Target Vessel-Myocardial Infarction (TV-MI) Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: TV-MI Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: TV-MI Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: TV-MI Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Procedural MI Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Procedural MI Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Procedural MI Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Procedural MI Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Non-Procedural MI Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Non-Procedural MI Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Non-Procedural MI Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Non-Procedural MI Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Ischemia-Driven Target Vessel Revascularization (ID-TVR) Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: ID-TVR Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: ID-TVR Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: ID-TVR Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR) Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: ID-TLR Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: ID-TLR Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: ID-TLR Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Non-ID-TVR Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Non-ID-TVR Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Non-ID-TVR Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Non-ID-TVR Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Non-ID-TLR Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Non-ID-TLR Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Non-ID-TLR Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Non-ID-TLR Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Any Revascularizations Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Any Revascularizations Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Any Revascularizations Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Any Revascularizations Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Stent Thrombosis Rate at 30 Days
timeFrame: within 30 days of index procedure
measure: Stent Thrombosis Rate at 6 Months
timeFrame: within 6 months of index procedure
measure: Stent Thrombosis Rate at 12 Months
timeFrame: within 12 months of index procedure
measure: Stent Thrombosis Rate at 24 Months
timeFrame: within 24 months of index procedure
measure: Rate of MI Using the 4th Universal Definition at 30 Days
timeFrame: within 30 days of index procedure
measure: Rate of MI Using the 4th Universal Definition at 6 Months
timeFrame: within 6 months of index procedure
measure: Rate of MI Using the 4th Universal Definition at 12 Months
timeFrame: within 12 months of index procedure
measure: Rate of MI Using the 4th Universal Definition at 24 Months
timeFrame: within 24 months of index procedure
measure: Rate of MI Using the Society for Cardiovascular Angiography and Interventions (SCAI) Definition at 30 Days
timeFrame: within 30 days of index procedure
measure: Rate of MI Using the SCAI Definition at 6 Months
timeFrame: within 6 months of index procedure
measure: Rate of MI Using the SCAI Definition at 12 Months
timeFrame: within 12 months of index procedure
measure: Rate of MI Using the SCAI Definition at 24 Months
timeFrame: within 24 months of index procedure
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD) - Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Advocate Health and Hospitals Corporation - Edward Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Heart Center of Indiana, LLC
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: MedStar Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University (NYU) Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/ New York Presbyterian
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Durham
country: United States
facility: Durham VA Health Care System
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart and Vascular
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Wormleysburg
country: United States
facility: Pinnacle Health Cardiovascular Institute Inc.
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Charleston
country: United States
facility: Charleston Area Medical Center (CAMC) - Health Education & Research Institute
state: West Virginia
city: Toulouse
country: France
facility: Clinique Pasteur
state: Cedex 3
city: Clermont-Ferrand
country: France
facility: Clinique des Domes - Pole Sante Republique
city: Massy
country: France
facility: Institute Cardiovasculaire Paris Sud
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen and Marburg GmbH
state: CET
city: Berlin
country: Germany
facility: Charité - Universitaetsmedizin Berlin
city: Neuss
country: Germany
facility: Rheinland Klinikum Neuss GmbH - Lukaskrankenhaus Neuss
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: The Christ Hospital Heart and Vascular Center and The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital
name: Dean J Kereiakes, MD,FACC,FSCAI
role: STUDY_CHAIR
affiliation: Columbia University
name: Gregg W Stone, MD,FACC,FSCAI
role: STUDY_CHAIR
affiliation: Royal Brompton and Harefield NHS Foundation Trust
name: Jonathan Hill, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.