Disrupt CAD III With the Shockwave Coronary IVL System

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03595176

Enrollment

431

Registered

2018-07-23

Start date

2019-01-09

Completion date

2022-04-10

Last updated

2023-05-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease, Myocardial Infarction

Keywords

Intravascular Lithotripsy, Percutaneous Coronary Intervention

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.

Interventions

DEVICELithotripsy

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

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.

Eligibility

Sex/Gender

ALL

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Who Experienced Freedom From Major Adverse Cardiac Events (MACE) Within 30 Days Post-procedure	within 30 days of index procedure	The primary safety endpoint was freedom from MACE at 30 days - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR). The primary endpoints were analyzed using the Pivotal Analysis Set.
Number of Participants With Procedural Success (Residual Stenosis <50%)	12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure	The primary effectiveness endpoint was Procedural Success defined as stent delivery with a residual in-stent stenosis \<50% (core laboratory assessed) and without in-hospital MACE. The primary endpoints were analyzed using the Pivotal Analysis Set.

Secondary

Measure	Time frame	Description
Number of Participants With Procedural Success (Residual Stenosis <=30%)	12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure	Procedural Success defined as stent delivery with a residual stenosis \<=30% (core laboratory assessed) and without in-hospital MACE. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Number of Participants With Angiographic Success (Residual Stenosis <=30%)	at end of procedure	Angiographic Success defined as stent delivery with \<=30% residual stenosis and without serious angiographic complications. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Number of Participants With Serious Angiographic Complications	at end of procedure	Serious Angiographic Complications defined as severe dissection (Type D to F), perforation, abrupt closure, and persistent slow flow or persistent no reflow. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MACE Rate at 6 Months	within 6 months of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MACE Rate at 12 Months	within 12 months of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MACE Rate at 24 Months	within 24 months of index procedure	MACE at 24 months - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR) - is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Target Lesion Failure (TLF) Rate at 30 Days	within 30 days of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Target Lesion Failure (TLF) Rate at 6 Months	within 6 months of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Target Lesion Failure (TLF) Rate at 12 Months	within 12 months of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Target Lesion Failure (TLF) Rate at 24 Months	within 24 months of index procedure	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 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
All-Cause Death Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
All-Cause Death Rate at 6 Months	within 6 months of index procedure	All-cause death at 6 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
All-Cause Death Rate at 12 Months	within 12 months of index procedure	All-cause death at 12 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
All-Cause Death Rate at 24 Months	within 24 months of index procedure	All-cause death at 24 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Cardiac Death Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Cardiac Death Rate at 6 Months	within 6 months of index procedure	Cardiac death at 6 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Cardiac Death Rate at 12 Months	within 12 months of index procedure	Cardiac death at 12 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Cardiac Death Rate at 24 Months	within 24 months of index procedure	Cardiac death at 24 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MI Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MI Rate at 6 Months	within 6 months of index procedure	MI is presented as a Kaplan-Meier estimated event rate at 6 months. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MI Rate at 12 Months	within 12 months of index procedure	MI is presented as a Kaplan-Meier estimated event rate at 12 months. The secondary endpoints were analyzed using the Pivotal Analysis Set.
MI Rate at 24 Months	within 24 months of index procedure	MI is presented as a Kaplan-Meier estimated event rate at 24 months. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Target Vessel-Myocardial Infarction (TV-MI) Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
TV-MI Rate at 6 Months	within 6 months of index procedure	TV-MI is presented as a Kaplan-Meier estimated event rate at 6 months. The secondary endpoints were analyzed using the Pivotal Analysis Set.
TV-MI Rate at 12 Months	within 12 months of index procedure	TV-MI is presented as a Kaplan-Meier estimated event rate at 12 months. The secondary endpoints were analyzed using the Pivotal Analysis Set.
TV-MI Rate at 24 Months	within 24 months of index procedure	TV-MI is presented as a Kaplan-Meier estimated event rate at 24 months. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Procedural MI Rate at 30 Days	within 30 days of index procedure	Periprocedural MI defined as CK-MB \> 3x upper limit of lab normal (ULN). 30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Procedural MI Rate at 6 Months	within 6 months of index procedure	Periprocedural MI defined as CK-MB \> 3x upper limit of lab normal (ULN). For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Procedural MI Rate at 12 Months	within 12 months of index procedure	Periprocedural MI defined as CK-MB \> 3x upper limit of lab normal (ULN). For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Procedural MI Rate at 24 Months	within 24 months of index procedure	Periprocedural MI defined as CK-MB \> 3x upper limit of lab normal (ULN). For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-Procedural MI Rate at 30 Days	within 30 days of index procedure	Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). 30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-Procedural MI Rate at 6 Months	within 6 months of index procedure	Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-Procedural MI Rate at 12 Months	within 12 months of index procedure	Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-Procedural MI Rate at 24 Months	within 24 months of index procedure	Non-Procedural MI defined as spontaneous MI beyond discharge (4th Universal Definition). For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Ischemia-Driven Target Vessel Revascularization (ID-TVR) Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
ID-TVR Rate at 6 Months	within 6 months of index procedure	For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
ID-TVR Rate at 12 Months	within 12 months of index procedure	For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
ID-TVR Rate at 24 Months	within 24 months of index procedure	For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Ischemia-Driven Target Lesion Revascularization (ID-TLR) Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
ID-TLR Rate at 6 Months	within 6 months of index procedure	For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
ID-TLR Rate at 12 Months	within 12 months of index procedure	For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
ID-TLR Rate at 24 Months	within 24 months of index procedure	For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TVR Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TVR Rate at 6 Months	within 6 months of index procedure	For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TVR Rate at 12 Months	within 12 months of index procedure	For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TVR Rate at 24 Months	within 24 months of index procedure	For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TLR Rate at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TLR Rate at 6 Months	within 6 months of index procedure	For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TLR Rate at 12 Months	within 12 months of index procedure	For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Non-ID-TLR Rate at 24 Months	within 24 months of index procedure	For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Any Revascularizations Rate at 30 Days	within 30 days of index procedure	Any revascularizations (ID and non-ID) at 30 days. 30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Any Revascularizations Rate at 6 Months	within 6 months of index procedure	Any revascularizations (ID and non-ID) at 6 months, presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Any Revascularizations Rate at 12 Months	within 12 months of index procedure	Any revascularizations (ID and non-ID) at 12 months, presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Any Revascularizations Rate at 24 Months	within 24 months of index procedure	Any revascularizations (ID and non-ID) at 24 months, presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Stent Thrombosis Rate at 30 Days	within 30 days of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Stent Thrombosis Rate at 6 Months	within 6 months of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Stent Thrombosis Rate at 12 Months	within 12 months of index procedure	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. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Stent Thrombosis Rate at 24 Months	within 24 months of index procedure	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 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the 4th Universal Definition at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Number of Participants With Device Crossing Success	at end of procedure	Device Crossing Success defined as the ability to deliver the IVL catheter across the target lesion, and delivery of lithotripsy without serious angiographic complications immediately after IVL. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the 4th Universal Definition at 12 Months	within 12 months of index procedure	For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the 4th Universal Definition at 24 Months	within 24 months of index procedure	For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the Society for Cardiovascular Angiography and Interventions (SCAI) Definition at 30 Days	within 30 days of index procedure	30-day rates are presented as proportions. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the SCAI Definition at 6 Months	within 6 months of index procedure	For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the SCAI Definition at 12 Months	within 12 months of index procedure	For 12 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the SCAI Definition at 24 Months	within 24 months of index procedure	For 24 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Rate of MI Using the 4th Universal Definition at 6 Months	within 6 months of index procedure	For 6 months, rates are presented as Kaplan-Meier estimated event rates. The secondary endpoints were analyzed using the Pivotal Analysis Set.
Number of Participants With Angiographic Success (Residual Stenosis <50%)	at end of procedure	Angiographic Success defined as stent delivery with \<50% residual stenosis and without serious angiographic complications. The secondary endpoints were analyzed using the Pivotal Analysis Set.

Countries

France, Germany, United Kingdom, United States

Participant flow

Recruitment details

Study recruitment and enrollment took place at 47 global centers including 38 in the United States and 9 in Europe between January 9, 2019 and March 27, 2020. A total of 431 subjects with de novo, calcified, stenotic, coronary arteries were enrolled and treated with the Coronary Intravascular Lithotripsy (IVL) System.

Pre-assignment details

431 subjects were enrolled into the study. The definition of enrollment is when the subject signs informed consent, meets all inclusion criteria, none of the exclusion criteria, and the IVL catheter has been inserted over a 0.014 guidewire which had been previously passed across the study lesion.

Participants by arm

Arm	Count
Coronary IVL System (Roll-In) The first subject enrolled at each site is considered a roll-in. Per protocol, data on roll-in subjects were collected through 30 days, at which time subject participation was complete.	47
Coronary IVL System (Pivotal) The pivotal analysis set was the primary analysis cohort used to assess the primary safety and effectiveness endpoints. Data on pivotal subjects was collected through 30 days for primary endpoints. Long-term follow-up for pivotal subjects to 24 months is complete.	384
Total	431

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	0	2
Overall Study	Lost to Follow-up	0	1

Baseline characteristics

Characteristic	Coronary IVL System (Roll-In)	Coronary IVL System (Pivotal)	Total
Age, Continuous	70.3 years STANDARD_DEVIATION 7.6	71.2 years STANDARD_DEVIATION 8.6	71.1 years STANDARD_DEVIATION 8.5
Age, Customized Median (Q1, Q3)	72.0 years	71.0 years	71.0 years
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	16 Participants	17 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants	330 Participants	371 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants	38 Participants	43 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Asian	2 Participants	13 Participants	15 Participants
Race (NIH/OMB) Black or African American	3 Participants	12 Participants	15 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants	38 Participants	45 Participants
Race (NIH/OMB) White	35 Participants	318 Participants	353 Participants
Region of Enrollment Europe	9 Participants	49 Participants	58 Participants
Region of Enrollment United States	38 Participants	335 Participants	373 Participants
Sex: Female, Male Female	12 Participants	90 Participants	102 Participants
Sex: Female, Male Male	35 Participants	294 Participants	329 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 47	2 / 384	7 / 384	22 / 384
other Total, other adverse events	15 / 47	54 / 384	140 / 384	162 / 384
serious Total, serious adverse events	4 / 47	54 / 384	136 / 384	173 / 384

Outcome results

Primary

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 at 30 days - a composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR). The primary endpoints were analyzed using the Pivotal Analysis Set.

Time frame: within 30 days of index procedure

Population: Data collected from the roll-in subjects were not pre-specified to be reported as a Primary Outcome Measure; therefore, only pivotal group is reported. Additionally, one subject was excluded from the primary safety endpoint analysis due to insufficient follow-up (\<23 days).

Arm	Measure	Value (NUMBER)
Coronary IVL System (Pivotal)	Number of Participants Who Experienced Freedom From Major Adverse Cardiac Events (MACE) Within 30 Days Post-procedure	92.2 percentage of participants

Primary

Number of Participants With Procedural Success (Residual Stenosis <50%)

The primary effectiveness endpoint was Procedural Success defined as stent delivery with a residual in-stent stenosis \<50% (core laboratory assessed) and without in-hospital MACE. The primary endpoints were analyzed using the Pivotal Analysis Set.

Time frame: 12-24 hours post procedure or at discharge, whichever is earlier, but at least 6 hours post procedure

Population: Data collected from the roll-in subjects were not pre-specified to be reported as a Primary Outcome Measure; therefore, only pivotal group is reported.

Arm	Measure	Value (NUMBER)
Coronary IVL System (Pivotal)	Number of Participants With Procedural Success (Residual Stenosis <50%)	92.4 percentage of participants

Secondary

All-Cause Death Rate at 12 Months

All-cause death at 12 months is presented as a Kaplan-Meier estimated event rate. The secondary endpoints were analyzed using the Pivotal Analysis Set.

Time frame: within 12 months of index procedure