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)
Phase: NA
Conditions: Coronary Artery Disease, Myocardial Infarction
Sponsor: Shockwave Medical, Inc.

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 1 of 7 
Study Title: 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) 
 
NCT Number: NCT 05966662 
 
IDE Number: G230172 
 
Protocol Number: CP-68277 
 
Protocol Date: 11 AUG 2023 
 
 

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 2 of 7 
Shockwave Disrupt CAD Duo Study Synopsis 
 
Investigational Plan/ 
Study/Protocol 
Number: 
Disrupt CAD Duo Study - CP-68277 
Study Title 
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). 
Study Objective 
The objective of 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. 
Study Device 
Shockwave C2+ 2Hz Coronary IVL Catheter with Shockwave Intravascular Lithotripsy 
(IVL) System 
Manufacturer 
Shockwave Medical, Inc. 
Investigational 
Indication for Use 
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. 
Study Design 
Prospective, multicenter, single-arm, IDE study. It is a confirmatory study designed to 
assess non-inferiority of the primary safety and effectiveness endpoints to a 
propensity-matched cohort from the Disrupt CAD III IDE study. 
Enrollment/ Number 
of Sites 
Up to 145 subjects (138 evaluable) will be enrolled at up to 20 US sites. Each site will 
be allowed to enroll a maximum of 15% (22 subjects) of the total study enrollment. 
Subject Population 
Subjects with de novo, calcified coronary artery lesions presenting with stable, 
unstable, or silent ischemia that are suitable for percutaneous coronary intervention 
(PCI). 
Study Duration/ 
Follow-Up Period 
Enrollment duration: approximately 10-12 months Study duration: approximately       
2 years. Subjects will be followed through discharge, 30 days, 6, and 12 months 
Primary Safety 
Endpoint 
Safety will be assessed by freedom from major adverse cardiac events (MACE) 
within 30 days of the index procedure. MACE is defined as: 
• Cardiac death; or 
• Myocardial Infarction (MI) (using the SCAI definition for peri-procedural MI; 
using the 4th Universal Definition for spontaneous MI beyond discharge); or 
• Target Vessel Revascularization (TVR) defined as revascularization at the 

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 3 of 7 
target vessel (inclusive of the target lesion) after the completion of the index 
procedure 
Primary Effectiveness 
Endpoint 
Procedural Success defined as stent delivery with a residual stenosis ≤30 % (core 
laboratory assessed) and without in-hospital MACE. 
Secondary Endpoints 
• 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. 
• Angiographic Success defined as stent delivery with <50% residual stenosis 
and without serious angiographic complications. 
• Procedural Success defined as stent delivery with a residual stenosis <50% 
(core laboratory assessed) and without in-hospital MACE. 
• Angiographic Success defined as stent delivery with ≤30% residual stenosis and 
withouserious angiographic complications. 
• Serious angiographic complications defined as severe dissection (Type D to F), 
perforation, abrupt closure, and persistent slow flow or persistent no reflow. 
• MACE at 6, and 12 months. 
• Target lesion failure (TLF) 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 at 30 days, 
6, 12 months. 
• At each time period: All death, cardiac death, MI, TV-MI, procedural and 
nonprocedural MI, ID-TVR, ID-TLR, ID-non-TLR ID-non-TVR, all 
revascularizations (ID and non-ID), and stent thrombosis (ARC definite, 
probable, definite or probable). 
• MI at each time period using alternative definitions for peri-procedural MI (Fourth 
Universal Definition and CK-MB > 3x ULN). 
Optical Coherence 
Tomography (OCT) 
Sub-study 
An OCT Sub-study will be conducted on up to 60 subjects at sites that routinely 
perform OCT imaging as standard of care, and OCT images will be analyzed by an 
independent core laboratory. OCT imaging will be completed at three time-points 
during the index procedure. 
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 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) 
4. 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. 
a. 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) 

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 4 of 7 
b. 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. 
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 criterion; 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. Non-target lesions requiring PCI may be treated either: 
a. >30 days prior to the study procedure if the procedure was 
unsuccessful or complicated; or 
b. >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 
c. >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 
a. Stenosis of ≥70% and <100%, or 
b. 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 participating in another research study involving an investigational 

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 5 of 7 
agent (pharmaceutical, biologic, or medical device) that has not reached the 
primary endpoint 
3. Subject is pregnant or nursing (a negative pregnancy test is required for 
women of child- bearing potential within 7 days prior to enrollment) 
4. Unable to tolerate antiplatelet/anticoagulation therapy per society guidelines 
5. Subject has an allergy to imaging contrast media which cannot be 
adequately pre- medicated 
6. 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 
7. New York Heart Association (NYHA) class III or IV heart failure 
8. Subject has acute or chronic renal disease with eGFR <30 ml/min/1.73m2 
(using CKD-EPI formula) 
9. History of a stroke or transient ischemic attack (TIA) within 60 days, or any 
prior intracranial hemorrhage or permanent neurologic deficit 
10. Active peptic ulcer or upper gastrointestinal (GI) bleeding within 3 months 
11. Untreated pre-procedural hemoglobin <10 g/dL or intention to refuse blood 
transfusions if one should become necessary 
12. 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) 
13. Subject has a hypercoagulable disorder such as polycythemia vera, platelet 
count >750,000 or other related blood disorders 
14. Subject has an active systemic infection on the day of the index procedure 
with either fever, leukocytosis or requiring intravenous antibiotics 
15. Subjects with clinical evidence of cardiogenic shock 
16. Uncontrolled severe hypertension (systolic BP >180 mm Hg or diastolic BP >110 
mm Hg) 
17. Subjects with a life expectancy of less than 1 year 
18. 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 
19. 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 
20. Subject refusing or not a candidate for emergency coronary artery bypass 
grafting (CABG) surgery 
21. Planned use of atherectomy, scoring or cutting balloon, or any investigational 
device other than lithotripsy 
Angiographic Exclusion Criteria 
22. Unprotected left main diameter stenosis >30% 
23. Definite or possible thrombus (by angiography or intravascular imaging) in 
the target vessel 
24. Evidence of aneurysm in target vessel within 10 mm of the target lesion 

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 6 of 7 
25.  Target lesion is located in a native vessel that can only be reached by going 
through a saphenous vein or arterial bypass graft 
26. Previous stent within 5 mm of the target lesion regardless of the timing of its 
implantation 
27. Angiographic evidence of a dissection or perforation in the target vessel at 
baseline or after guidewire passage 
Statistical Methods 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The primary safety and effectiveness endpoints in the Disrupt CAD Duo study will be 
compared to a similar set of subjects from the Disrupt CAD III study using a 
propensity-score matched analysis and a non-inferiority design.   
 
Primary Safety Endpoint 
In the Disrupt CAD III study, freedom from 30-day MACE was 96.3% (369/383) using 
the SCAI definition for peri-procedural MI.  
The null and alternative hypotheses for the primary safety endpoint are as follows: 
H0: ΠS,C2+ ≤ ΠS,CAD III – δS 
HA: ΠS,C2+ > ΠS,CAD III – δS 
where ΠS,C2+ is the true 30-day freedom from MACE rate in the Disrupt CAD Duo study, 
ΠS,CAD III is the true 30-day freedom from MACE rate in the propensity-matched Disrupt 
CAD III cohort (using the SCAI definition for peri-procedural MI), and δS is the pre-
specified margin of non-inferiority. The assumptions for the sample size calculations 
are listed below.  
• Expected 30-day freedom from MACE rate for the Disrupt CAD Duo study (ΠS,C2+) 
= 96.3% 
• Expected 30-day freedom from MACE rate in Disrupt CAD III propensity-matched 
cohort (using the SCAI definition for peri-procedural MI) (ΠS,CAD III) = 96.3% 
• Margin of non-inferiority (δS) = 7% 
• One-sided statistical significance level (α) = 0.05 
• Two-sample Farrington-Manning non-inferiority test of binomial proportions 
• 1:2 propensity score matching (Disrupt CAD Duo:Disrupt CAD III) 
Based on the above assumptions, a sample size of 138 evaluable subjects provides a 
statistical power of 90.0% for safety. Up to 145 subjects may be enrolled to account for 
attrition. 
Primary Effectiveness Endpoint 
In the Disrupt CAD III study, Procedural Success was 96.4% (370/384) (defined as 
≤ 30% final residual stenosis with no in hospital MACE using the SCAI definition for 
peri-procedural MI). 
The null and alternative hypotheses for the primary effectiveness endpoint are as 
follows: 
H0: ΠE,C2+ ≤ ΠE,CAD III – δE 
HA: ΠE,C2+ > ΠE,CAD III – δE 

 
 
DISRUPT CAD DUO PROTOCOL SYNOPSIS 
NCT05966662 
 
 
Conﬁdential – This document is property of Shockwave Medical, Inc. 
Page 7 of 7 
 
where ΠE,C2+ is the true Procedural Success rate in the Disrupt CAD Duo study, 
ΠE,CAD III is the true Procedural Success rate in the propensity-matched Disrupt CAD III 
cohort (using the SCAI definition for peri-procedural MI and ≤ 30% final residual 
stenosis), and δE is the pre-specified margin of non-inferiority. The assumptions for the 
sample size calculations are listed below.  
• Expected Procedural Success rate for the Disrupt CAD Duo study (ΠE,C2+) = 96.4% 
• Expected Procedural Success rate in Disrupt CAD III propensity-matched cohort 
(using the SCAI definition for peri-procedural MI) (ΠE,CAD III) = 96.4% 
• Margin of non-inferiority (δE) = 7% 
• One-sided statistical significance level (α) = 0.05 
• Two-sample Farrington-Manning non-inferiority test of binomial proportions 
• 1:2 propensity score matching (Disrupt CAD Duo:Disrupt CAD III) 
Based on the above assumptions, a sample size of 138 evaluable subjects provides 
a statistical power of 90.0% for effectiveness. Up to 145 subjects may be enrolled to 
account for attrition. The study will be deemed a success if both the primary safety 
and effectiveness endpoints are met. 
Study Sponsor / 
Study Management 
Shockwave Medical, Inc.  
5403 Betsy Ross Drive  
Santa Clara, CA 95054 USA 
 
Contact: Tracy Courtney 
Title: Assoc. Director, Clinical Affairs 
Telephone (direct): +1 (650) 244-7699 
E-mail: tcourtn4@its.jnj.com 
Angiographic & 
OCT Core Lab 
Cardiovascular Research Foundation  
1700 Broadway, 9th Floor 
New York, NY 10019 USA 
Clinical Events 
Committee 
Cardiovascular Research Foundation  
1700 Broadway, 9th Floor 
New York, NY 10019 USA 
Independent Data 
Safety Monitoring 
Board 
Cardiovascular Research Foundation  
1700 Broadway, 9th Floor 
New York, NY 10019 USA 
Clinical Research 
Organization (Site 
Management/ 
Monitoring / Central 
Lab) 
Medpace, Inc. 
5375 Medpace Way 
Cincinnati, OH 45227 USA