Shockwave C2+ 2Hz Coronary IVL Catheter in Calcified Coronary Arteries (Disrupt CAD DUO)

Study Overview
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Brief Summary
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This investigational device exemption (IDE) study is to assess the safety and effectiveness of the Shockwave Coronary Intravascular Lithotripsy (IVL) System with the Shockwave C2+ 2Hz Coronary IVL Catheter to treat de novo, calcified, stenotic, coronary lesions prior to stenting.

Detailed Description
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The Shockwave Coronary Intravascular Lithotripsy (IVL) System with the Shockwave C2+ 2Hz Coronary IVL Catheter is indicated for lithotripsy-enabled, low-pressure balloon dilatation of severely calcified, stenotic de novo coronary arteries prior to stenting. Up to 145 subjects (138 evaluable) subjects with de novo, calcified coronary artery lesions presenting with stable, unstable, or silent ischemia that are suitable for percutaneous coronary intervention (PCI) will be enrolled at up to 20 US sites. Enrollment duration will be approximately 10-12 months and study duration will be approximately 2 years. Each subject will be followed through discharge, 30 days, 6, and 12 months.

Official Title
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Prospective, Multicenter, Single-Arm IDE Study of the Shockwave Coronary Intravascular Lithotripsy (IVL) System With the Shockwave C2+ 2Hz Coronary IVL Catheter in Calcified Coronary Arteries (Disrupt CAD Duo Study)

Conditions
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Coronary Artery Disease, Myocardial Infarction

Intervention / Treatment
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* Device: IVL with Shockwave C2+ 2Hz Coronary IVL Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Subjects are required to meet all of the following inclusion criteria in order to be enrolled in the clinical study. General Inclusion Criteria Subject is ≥18 years of age Subjects with native coronary artery disease (including stable or unstable angina and silent ischemia) suitable for PCI For subjects with unstable ischemic heart disease, biomarkers (CK-MB and troponin) must be less than or equal to the upper limit of the laboratory normal within 12 hours prior to the procedure (note: both must be normal) For subjects 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 If drawn prior to the procedure, biomarkers (CK-MB and troponin) must be less than or equal to the upper limit of the laboratory normal within 12 hours of the procedure (note: both must be normal) If 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 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 criterion; may be assessed at time of index procedure) Subject or legally authorized representative, signs a written Informed Consent form to participate in the study, prior to any study-mandated procedures Non-target lesions requiring PCI may be treated either >30 days prior to the study procedure if the procedure was unsuccessful or complicated; or >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 >30 days after the study procedure Angiographic Inclusion Criteria The target lesion must be a de novo coronary lesion that has not been previously treated with any interventional procedure Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX (or of their branches) with Stenosis of ≥70% and <100%, or 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 The target vessel reference diameter must be ≥2.5 mm and ≤4.0 mm The lesion length must not exceed 40 mm The target vessel must have TIMI flow 3 at baseline (visually assessed; may be assessed after pre- dilatation) 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 Ability to pass a 0.014 guide wire across the lesion Exclusion Criteria: Subjects who meet any of the following exclusion criteria may not be enrolled in the study: General Exclusion Criteria Any comorbidity or condition which may reduce compliance with this protocol, including follow-up visits Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint Subject is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrollment) Unable to tolerate antiplatelet/anticoagulation therapy per society guidelines Subject has an allergy to imaging contrast media which cannot be adequately pre-medicated 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 greater than 1 times the local laboratory's upper limit of normal New York Heart Association (NYHA) class III or IV heart failure Subject has acute or chronic renal disease with eGFR <30 ml/min/1.73m2 (using CKD-EPI formula) History of a stroke or transient ischemic attack (TIA) within 60 days, or any prior intracranial hemorrhage or permanent neurologic deficit Active peptic ulcer or upper gastrointestinal (GI) bleeding within 3 months Untreated pre-procedural hemoglobin <10 g/dL or intention to refuse blood transfusions if one should become necessary 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) Subject has a hypercoagulable disorder such as polycythemia vera, platelet count >750,000 or other related blood disorders Subject has an active systemic infection on the day of the index procedure with either fever, leukocytosis or requiring intravenous antibiotics Subjects with clinical evidence of cardiogenic shock Uncontrolled severe hypertension (systolic BP >180 mm Hg or diastolic BP >110 mm Hg) Subjects with a life expectancy of less than 1 year 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 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 Subject refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery Planned use of atherectomy, scoring or cutting balloon, or any investigational device other than lithotripsy Angiographic Exclusion Criteria Unprotected left main diameter stenosis >30% Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel Evidence of aneurysm in target vessel within 10 mm of the target lesion Target lesion is located in a native vessel that can only be reached by going through a saphenous vein or arterial bypass graft Previous stent within 5 mm of the target lesion regardless of the timing of its implantation Angiographic evidence of a dissection or perforation in the target vessel at baseline or after guidewire passage

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Shockwave C2+ 2Hz Coronary IVL Catheter with Shockwave Intravascular Lithotripsy (IVL) System
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Arm<br>Subjects with de novo, calcified coronary artery lesions presenting with stable, unstable, or silent ischemia that are suitable for percutaneous coronary intervention (PCI). | Device: IVL with Shockwave C2+ 2Hz Coronary IVL Catheter<br>* Lithotripsy-enabled, low-pressure balloon dilatation of severely calcified, stenotic de novo coronary arteries prior to stenting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Freedom From Major Adverse Cardiac Events (MACE) Within 30 Days Post-procedure | The primary safety endpoint was freedom from MACE within 30 days of the index procedure. MACE is defined as a composite occurrence of: 1) Cardiac death; or 2) Myocardial Infarction (MI) (using the SCAI definition for peri-procedural MI; using the 4th Universal Definition for spontaneous MI beyond discharge); or 3) Target Vessel Revascularization (TVR) defined as revascularization at the target vessel (inclusive of the target lesion) after the completion of the index procedure | 30 days of the index procedure | 
| Number of Participants With Procedural Success (Residual Stenosis <30%) | The primary effectiveness endpoint will be evaluated as the following: Procedural Success defined as stent delivery with a residual stenosis ≤30% (core laboratory assessed) and without in-hospital MACE. | 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Device Crossing Success | Device Crossing Success is defined as the ability to deliver the IVL catheter across the target lesion, and delivery of lithotripsy without serious angiographic complications immediately after IVL. | at the end of procedure | 
| Number of Participants With Angiographic Success (Residual Stenosis <50%) | Angiographic Success defined as stent delivery with <50% residual stenosis and without serious angiographic complications. | at the end of procedure | 
| Number of Participants With Procedural Success (Residual Stenosis <=30%) | Procedural Success defined as stent delivery with a residual stenosis <50% (core laboratory assessed) and without in-hospital MACE. | 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure] | 
| Number of Participants With Angiographic Success (Residual Stenosis <=30%) | Angiographic Success defined as stent delivery with ≤30% residual stenosis and without serious angiographic complications. | at end of procedure | 
| Number of Participants With Serious Angiographic Complications | Serious angiographic complications defined as severe dissection (Type D to F), perforation, abrupt closure, and persistent slow flow or persistent no reflow. | at end of procedure | 
| MACE Rate at 6 Months | MACE at 6 months - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR) - is presented as a Kaplan-Meier estimated event rate. | within 6 months of index procedure | 
| MACE Rate at 12 Months | MACE at 12 months - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR) - is presented as a Kaplan-Meier estimated event rate. | within 12 months of index procedure | 
| Target Lesion Failure (TLF) Rate at 30 Days | Target lesion failure (TLF) is defined as cardiac death, target vessel myocardial infarction (Q wave and non-Q wave), or ischemia-driven target lesion revascularization (ID-TLR) by percutaneous or surgical methods. 30 day rates are presented as proportions. | within 30 days of index procedure | 
| Target Lesion Failure (TLF) Rate at 6 Months | TLF is defined as cardiac death, target vessel myocardial infarction (Q wave and non-Q wave), or ischemia-driven target lesion revascularization (ID-TLR) by percutaneous or surgical methods. For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Target Lesion Failure (TLF) Rate at 12 Months | TLF is defined as cardiac death, target vessel myocardial infarction (Q wave and non-Q wave), or ischemia-driven target lesion revascularization (ID-TLR) by percutaneous or surgical methods. For 12 months, rates are presented as Kaplan-Meier estimated event rates | within 12 months of index procedure | 
| All-Cause Death Rate at 30 Days | 30-day rates are presented as proportions. | within 30 days of index procedure | 
| All-Cause Death Rate at 6 Months | All-cause death at 6 months is presented as a Kaplan-Meier estimated event rate. | within 6 months of index procedure | 
| All-Cause Death Rate at 12 Months | All-cause death at 12 months is presented as a Kaplan-Meier estimated event rate. | within 12 months of index procedure | 
| Cardiac Death Rate at 30 Days | 30-day rates are presented as proportions | within 30 days of index procedure | 
| Cardiac Death Rate at 6 Months | Cardiac death at 6 months is presented as a Kaplan-Meier estimated event rate. | within 6 months of index procedure | 
| Cardiac Death Rate at 12 Months | Cardiac death at 12 months is presented as a Kaplan-Meier estimated event rate. | within 12 months of index procedure | 
| MI Rate at 30 Days | 30-day rates are presented as proportions. | within 30 days of index procedure | 
| MI Rate at 6 Months | MI is presented as a Kaplan-Meier estimated event rate at 6 months. | within 6 months of index procedure | 
| MI Rate at 12 Months | MI is presented as a Kaplan-Meier estimated event rate at 12 months. | within 12 months of index procedure | 
| Target Vessel-Myocardial Infarction (TV-MI) Rate at 30 Days | 30-day rates are presented as proportions. | within 30 days of index procedure | 
| TV-MI Rate at 6 Months | TV-MI is presented as a Kaplan-Meier estimated event rate at 6 months. | within 6 months of index procedure | 
| TV-MI Rate at 12 Months | TV-MI is presented as a Kaplan-Meier estimated event rate at 12 months. | within 12 months of index procedure | 
| Procedural MI Rate at 30 Days | Periprocedural MI defined as fourth universal definition and CK-MB > 3x upper limit of lab normal (ULN). 30-day rates are presented as proportions. | within 30 days of index procedure | 
| Procedural MI Rate at 6 Months | Periprocedural MI defined as fourth universal definition and CK-MB > 3x upper limit of lab normal (ULN). For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Procedural MI Rate at 12 Months | Periprocedural MI defined as fourth universal definition and CK-MB > 3x upper limit of lab normal (ULN). For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Non-Procedural MI Rate at 30 Days | Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). 30-day rates are presented as proportions. | within 30 days of index procedure | 
| Non-Procedural MI Rate at 6 Months | Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Non-Procedural MI Rate at 12 Months | Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Ischemia-Driven Target Vessel Revascularization (ID-TVR) Rate at 30 Days | 30-day rates are presented as proportions. | within 30 days of index procedure | 
| ID-TVR Rate at 6 Months | For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| ID-TVR Rate at 12 Month | For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Ischemia-Driven Target Lesion Revascularization (ID-TLR) Rate at 30 Days | 30-day rates are presented as proportions. | within 30 days of index procedure | 
| ID-TLR Rate at 6 Months | For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| ID-TLR Rate at 12 Months | For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Non-ID-TVR Rate at 30 Days | 30-day rates are presented as proportions | within 30 days of index procedure | 
| Non-ID-TVR Rate at 6 Months | For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Non-ID-TVR Rate at 12 Months | For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Non-ID-TLR Rate at 30 Days | 30-day rates are presented as proportions | within 30 days of index procedure | 
| Non-ID-TLR Rate at 6 Months | For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Non-ID-TLR Rate at 12 Months | For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Any Revascularizations Rate at 30 Days | Any revascularizations (ID and non-ID) at 30 days. 30-day rates are presented as proportions. | within 30 days of index procedure | 
| Any Revascularizations Rate at 6 months | Any revascularizations (ID and non-ID) at 6 months, presented as a Kaplan-Meier estimated event rate. | within 6 months of index procedure | 
| Any Revascularizations Rate at 12 months | Any revascularizations (ID and non-ID) at 12 months, presented as a Kaplan-Meier estimated event rate | within 12 months of index procedure | 
| Stent Thrombosis Rate at 30 Days | Any stent thrombosis (definite, probable, definite or probable) according to Academic Research Consortium (ARC) criteria, as referenced from Cutlip, D.E. et al. Clinical End Points in Coronary Stent Trials. Circ. 2007.115.2344-51. 30-day rates are presented as proportions. | within 30 days of index procedure | 
| Stent Thrombosis Rate at 6 Months | Any stent thrombosis (definite, probable, definite or probable) according to Academic Research Consortium (ARC) criteria, as referenced from Cutlip, D.E. et al. Clinical End Points in Coronary Stent Trials. Circ. 2007.115.2344-51. For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Stent Thrombosis Rate at 12 Months | Any stent thrombosis (definite, probable, definite or probable) according to Academic Research Consortium (ARC) criteria, as referenced from Cutlip, D.E. et al. Clinical End Points in Coronary Stent Trials. Circ. 2007.115.2344-51. For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 
| Rate of MI Using the 4th Universal Definition at 30 Days | 30-day rates are presented as proportions. | within 30 days of index procedure | 
| Rate of MI Using the 4th Universal Definition at 6 months | For 6 months, rates are presented as Kaplan-Meier estimated event rates. | within 6 months of index procedure | 
| Rate of MI Using the 4th Universal Definition at 12 months | For 12 months, rates are presented as Kaplan-Meier estimated event rates. | within 12 months of index procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravasular Lithotripsy, PCI