Prospective Multi-Center, Single Arm Post-Market Study (PMS) of the Shockwave Medical, Inc. Coronary Lithoplasty® System in Coronary Arteries
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Shockwave Medical, Inc.

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
 
 
Study Title: Prospective Multi-Center, Single Arm Post-Market Study 
(PMS) of the Shockwave Medical, Inc. Coronary Lithoplasty® System 
in Coronary Arteries  (Disrupt CAD II) 
 
NCT Number: 03328949 
 
Date: October 18, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
 
Investigational 
Plan/Study/Protocol Number: 
Disrupt CAD II Study - CP 61774 
Study Title: 
Prospective Multi-Center, Single Arm Post-Market Study 
(PMS) of the Shockwave Medical, Inc. Coronary Lithoplasty® 
System in Coronary Arteries 
Study Objective: 
The objective of the study is to assess the safety and 
performance of the Shockwave Medical, Inc. Coronary 
Lithoplasty® System to treat calcified, stenotic, de novo 
coronary lesions prior to stenting in a real-world post-market 
study. 
Study Device: 
Coronary Intravascular Lithotripsy (IVL) (previously referred 
to as Lithoplasty®) System by Shockwave Medical, Inc. 
Indications for Use: 
The Shockwave Medical Coronary IVL System is indicated for 
lithotripsy-enhanced, low-pressure balloon dilatation of 
calcified, stenotic de novo coronary arteries prior to stenting.  
Study Design: 
Prospective, multi-center, single arm post market study to 
evaluate the real-world safety and performance of the Coronary 
IVL System for lithotripsy-enhanced, low-pressure balloon 
dilatation of calcified, stenotic de novo coronary arteries prior 
to stenting.  
Enrollment/ Number of Sites: 
Maximum of 120 subjects at up to 15 sites in Europe. 
Subject Population: 
Patients ≥18 years of age scheduled for a coronary stent 
procedure who have angiographic evidence of significant 
calcified stenosis of the left main coronary artery (LMCA), left 
anterior descending artery (LAD), right coronary artery (RCA), 
or left circumflex (LCX). 
Study Duration/ Follow-Up 
Period: 
Approximately 8 to 10 months of enrollment at 15 European 
sites. Subjects will be followed through discharge and at 30 
days by phone follow-up. 
Primary Safety Endpoint: 
In-hospital major adverse cardiac events (MACE) 
Secondary Endpoints: 
Performance will be assessed by the ability of the Lithoplasty 
System to produce acceptable residual stenosis (<50%) after 
stenting with no evidence of in-hospital MACE.  Each patient 
that achieves both of these requirements will be considered a 
“clinical success”, and the rate of clinical success among 
subjects will be evaluated. 
Angiographic success defined as success in facilitating stent 
delivery with <50% residual stenosis and without serious 
angiographic 
complications. 
Serious 
angiographic 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
complications are defined as severe dissection (Type D to F), 
perforation, abrupt closure, and persistent slow flow or 
persistent no reflow. 
Cardiac death at 30 days. 
Inclusion Criteria: 
1. Patient is > 18 years of age 
2. Troponin must be less than or equal to the upper limit of 
lab normal value within 24 hours prior to the procedure 
OR if troponin is elevated, concomitant CK must be 
normal. 
3. The target vessel must have a TIMI flow 3 at baseline 
4. Patients with significant (≥ 50% diameter stenosis) 
native coronary artery disease including stable or 
unstable angina and silent ischemia, suitable for PCI 
5. Ability to tolerate dual antiplatelet agent (i.e. aspirin, 
clopidogrel,  prasugrel, or ticagrelor for 1 year and 
single antiplatelet therapy for life 
6. Single lesion stenosis of protected LMCA, or LAD, 
RCA or LCX artery ≥50% in a reference vessel of 2.5 
mm - 4.0 mm diameter and ≤ 32 mm length 
7. Presence of calcification within the lesion on both sides 
of the vessel as assessed by angiography 
8. Planned treatment of single lesion in one vessel 
9. Ability to pass a 0.014” guide wire across the lesion  
10. Patient, or authorized representative, signs a written 
Informed Consent form to participate in the study, prior 
to any study-mandated procedures 
11. Patient is able and willing to comply with all 
assessments in the study 
Exclusion Criteria: 
1. Concomitant use of Atherectomy, specialty balloon, or 
investigational coronary devices 
2. Prior PCI procedure within the last 30 days of the index 
procedure 
3. Patient has planned cardiovascular interventions within 
30 days post index procedure 
4. Second lesion with ≥50% stenosis in the same target 
vessel 
5. Left ventricular ejection fraction < 40% 
6. Patient refusing or not a candidate for emergency 
coronary artery bypass grafting (CABG) surgery 
7. Uncontrolled severe hypertension (systolic BP >180 mm 
Hg or diastolic BP >110 mm Hg) 
8. Severe renal failure with serum creatinine >2.5 mg/dL, 
unless on chronic dialysis 
9. Untreated pre-procedural hemoglobin <10 g/dL 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
10. Coagulopathy manifested by platelet count <100,000 or 
International Normalized ratio (INR) >1.7 (INR is only 
required in patients who have taken warfarin within 2 
weeks of enrollment) 
11. Patients in cardiogenic shock 
12. Acute myocardial infarction (MI) within the past one (1) 
month, and/or signs of active myocardial ischemia at the 
time of enrollment including elevated Troponin-I or T 
(with concomitant elevation of CK), ischemic ECG 
changes or chest pain 
13. History of a stroke or transient ischemic attack (TIA) 
within 3 months 
14. NYHA class III or IV heart failure 
15. Active peptic ulcer or upper gastrointestinal (GI) 
bleeding within 6 months 
16. Patients with a life expectancy of less than 1 year 
17. Target vessel < 2.4 mm in diameter 
18. Target lesion > 32 mm in length 
19. Chronic Total Occlusion (CTO) 
20. Previous stent procedure within 5 mm of target lesion 
21. Angiographic evidence of a target lesion severe 
dissection prior to Coronary Lithoplasty treatment 
22. Unprotected Left Main diameter stenosis ≥ 50% 
23. Visible thrombus (by angiography) at target lesion site 
24. Target lesion is located in a native vessel distal to 
anastomosis with a saphenous vein graft or 
LIMA/RIMA bypass 
25. Patient has active systemic infection 
26. Patient has connective tissue disease (e.g., Marfan’s 
syndrome) 
27. Patient has a hypercoagulable disorder 
28. Uncontrolled insulin dependent diabetes 
29. Patient has allergy to imaging contrast media for which 
they cannot be pre-medicated 
30. Evidence of aneurysm in target vessel 
31. Patient is pregnant or nursing 
Sponsor: 
Shockwave Medical, Inc. 
5403 Betsy Ross Drive 
Santa Clara, CA 95054 
United States of America 
 
 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
1 INTRODUCTION 
 Background 
Challenges in Treating Calcified Plaque  
Calcified coronary lesions are associated with age, diabetes and chronic kidney disease.(1)     
Approximately 38% and 73% of all coronary artery lesions display calcification as detected 
by angiography and intravascular ultrasound (IVUS), respectively.  As IVUS is not routinely 
used as a diagnostic modality, coronary calcification is most likely underestimated.(2)  
Calcification adversely impacts interventional outcomes by complicating device delivery(3), 
damaging the drug-eluting polymer(4) and impairing stent expansion and apposition(5).   
Current Therapies 
Current therapies used to overcome these limitations include high-pressure balloon dilation 
and atherectomy.  However, balloon angioplasty is limited in its ability to modify calcific 
plaque.  Dilatation in eccentric calcium may be biased by the guidewire towards the non-
calcified segments of the artery, and in concentric calcium may be of insufficient pressure-
generated force to lead to calcium fracture and vessel expansion.   
Rotational and orbital atherectomy selectively ablate superficial calcium increasing stent 
deliverability but have limited impact on deep calcium that limits vessel expansion during 
stent implantation(5,6).  In addition, peri-procedural complications including perforation, slow 
flow and peri-procedural myocardial infarction (MI) are still significantly higher with 
atherectomy than balloon-based therapies.(7,8,9,10,11) 
Abdel-Waheb et al reported a 1.7% perforation rate following treatment with rotablator plus 
drug eluting stent (DES).  At 9 months, rotational atherectomy (RA) had similar rates of 
binary restenosis, target lesion revascularization (TLR), stent thrombosis and MACE, despite 
a higher procedural acute gain over PTCA.  Chambers et al reported the 30-day orbital 
atherectomy (OA) results from the ORBIT II Study.  OA procedural success, defined as less 
than 50% residual stenosis after stenting and no in-hospital MACE, was 88.9%.  In addition, 
percent residual stenosis following stenting was low at 5.8%.  Angiographic complications 
included severe dissection and abrupt closure of 3.4% and 1.8%, and in-hospital non-Q wave 
MI’s occurred in 8.6% of the subjects.(12) 
Shockwave Medical Coronary Intravascular Lithotripsy (IVL)  
Intravascular Lithotripsy (IVL) is a technique based on lithotripsy, an established treatment 
strategy for renal calculi, in which multiple lithotripsy emitters mounted on a traditional 
balloon catheter platform create diffusive pulsatile mechanical energy to disrupt calcium 
within the vessel wall at low inflation pressures.  The completed Disrupt CAD I Study 
reported the safety and performance of coronary IVL in vessel preparation for calcified, 
stenotic, de novo coronary lesions prior to stent implantation.  
 
 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
Disrupt CAD I Study 
Successful delivery of the IVL balloon was achieved in 59 (98.5%) subjects with reduction in 
residual stenosis to less than 50% in all 60 (100%) subjects.  The angiographic luminal acute 
gain following stent implantation was 1.7 mm and residual stenosis was 13.3%.  Freedom 
from MACE was present in 57 (95%) subjects due to 3 (5%) non-Q wave MI at 30 days.  At 
6 months, freedom from MACE was present in 54 of 59 (91.5%) subjects due to 2 additional 
subjects suffering cardiac death.  Results of the optical coherence tomography (OCT) sub-
study identified modification with fracture as a major mechanism of action of IVL in vivo 
and demonstrated efficacy in the achievement of significant acute area gain and favorable 
stent expansion.(13) 
As a result of the CAD I study meeting its primary and secondary endpoints and being able 
to demonstrate a strong safety profile throughout the study, the coronary IVL system 
received CE marking in Europe on 18 April 2017.  
 Rationale for Disrupt CAD II Study 
The Disrupt CAD II post-market surveillance study was initiated in May 2018 to evaluate the 
real-world safety and performance of the Coronary IVL System and to ensure that pre-market 
study outcomes from CAD I were generalizable to a broader population with a larger number 
of physician users. 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
2 STUDY DEVICE DESCRIPTION 
The Coronary Lithoplasty System is a proprietary balloon catheter system designed to enhance 
PTCA by enabling delivery of the calcium disrupting capability of lithotripsy prior to balloon 
dilatation at low pressures. The Coronary Lithoplasty System consists of a Lithoplasty Balloon 
Catheter with two integrated pairs of lithotripsy emitters, a Lithoplasty Generator, Connector 
Cable, and related accessories.  
The Lithoplasty Catheter consists of a standard PTCA catheter with two lithotripsy emitters 
incorporated into the 12 mm balloon section of the catheter. The balloon is inflated at a lower 
than nominal pressure and the lithotripsy emitters are energized thereby generating pulsatile 
mechanical energy within the balloon at the target treatment site, disrupting calcium within the 
lesion, and allowing subsequent dilation of a coronary artery stenosis using low balloon pressure 
prior to stenting.   
The Lithoplasty Catheters are  available in 7 sizes: 2.5 mm, 2.75mm, 3.0 mm, 3.25 mm, 3.5mm, 
3.75 mm, and 4.0 mm diameter and 12 mm length. The Rapid Exchange (Rx) Catheter has a 
working length of 138 cm and is compatible with 190 or 300 cm length 0.014” guidewires.  The 
Lithoplasty Catheter has compatibility with guide catheters as specified in the Instructions for 
Use (IFU). The Lithoplasty Catheter dual-lumen hub contains an inflation lumen, and the 
Catheter Connector. The inflation port is used for inflation of the balloon with 50/50 
saline/contrast medium, as is standard practice with standard PTCA balloons. The Catheter 
Connector port facilitates connection to the Connector Cable.  
The Lithoplasty Generator design is used to support all sizes of Lithoplasty Catheters and the 
software can detect the different Lithoplasty Catheter types and sizes through a unique PCB 
incorporated inside the Lithoplasty Catheter.  The Connector Cable connects the Generator to the 
Lithoplasty Catheter and includes a remote actuator used to activate the energy delivery from the 
Generator to the Lithoplasty Catheter.  The Lithoplasty Catheter is used exclusively with the 
Shockwave Medical Lithoplasty Generator and Connector Cable.  
The Lithoplasty Catheter is supplied sterile via e-beam sterilization.  It is intended for single use 
only and is not intended for reuse or re-sterilization. The Lithoplasty Generator and Connector 
Cable are non-sterile and reusable. 
 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
3 STATISTICAL CONSIDERATIONS 
 Statistical Methods  
 Sample Size Justification 
The primary objective of the study is to confirm if the true primary endpoint rate meets the 
upper bound of the 95% confidence interval. 
Key assumptions: 
 One-sided alpha = 0.05 
 True rate of 7.7% 
 Upper bound of 95% confidence interval = 13% 
 Sample size = 120 subjects 
 Maximum number of events with 120 subjects = 9 
 Analysis Populations 
The primary analysis dataset was the Intent-To-Treat (ITT) population which included all 
enrolled subjects.   
The secondary analysis set was the Per-Protocol (PP) population which included subjects 
with no pre-specified inclusion or exclusion violations.  
No imputation of or adjustments for missing data were performed for the primary or 
secondary analyses.   
 Primary Endpoint Analysis 
The primary safety endpoint was the frequency of in-hospital major adverse cardiac events 
(MACE).  MACE was defined as the following: 
 Cardiac death 
 MI - defined as a CK-MB level > 3 times the upper limit of lab normal (ULN) value with 
or without new pathologic Q wave 
 TVR - defined as revascularization at the target vessel (inclusive of the target lesion) after 
the completion of the index procedure 
Number and proportions of subjects with any type of MACE were reported. No formal 
hypothesis testing was performed; however, 95% confidence intervals were provided for the 
primary safety endpoint.   
 Secondary Endpoint Analyses 
Clinical Success: The number and proportion of subjects achieving clinical success were 
defined by subjects achieving both of the following requirements: 
 Ability of the Coronary Lithotripsy System to produce acceptable residual stenosis 
(<50%) after stenting 
 No evidence of in-hospital MACE 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
Angiographic Success: The number and proportion of subjects achieving angiographic 
success were defined as success in facilitating stent delivery with <50% residual stenosis 
without 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. 
Cardiac Death: The number and proportion of subjects who experience cardiac death within 
30 days of the lithotripsy procedure. 
The lower 95% CI limit for clinical success and 2-sided 95% CI limit for angiographic 
success and cardiac death rate within 30 days of the lithotripsy procedure were reported. 
 Study Assessments 
 Schedule of Events 
Table 1 summarizes the schedule of events and assessments for study subjects required by 
protocol Revision C. 
Table 1.  Schedule of Events 
Assessment 
Screening/ 
Baseline 
(Day -14 to 
Day 0) 
Enrollment 
and 
Procedure 
(Day 0) 
Post 
Treatment 
Discharge 
30 Days 
(+/- 7D)3 
Informed Consent 
X 
 
 
 
 
Medical History  
X 
 
 
 
 
Physical Examination 
X 
 
 
X 
 
NYHA Classification 
X 
 
 
 
 
Canadian Cardiovascular Society (CCS) 
Angina Classification 
X 
 
 
 
 
Laboratory Assessments 
CK, Platelets, 
Creatinine, 
Hemoglobin, 
BUN 
Troponin2 
 
Troponin, 
CK, 
CK-MB, 
Creatinine, 
Hemoglobin 
 
Urine pregnancy test, if female of 
childbearing potential within 7 days of 
procedure 
X 
 
 
 
 
LVEF 
X1 
 
 
 
 
ECG 
X 
 
 
X 
 
Coagulation Studies: PT/PTT INR 
X 
 
 
 
 
Angiographic Lesion Assessment 
 
X 
X 
 
 
Medication regimen per protocol 
X 
 
 
X 
X 
Adverse Event Assessment 
 
X 
X 
X 
X 
1 Screening/baseline LVEF results must be within 90 days of procedure 
2 Troponin to be collected and analyzed within 24 hours prior to procedure 
3 Telephone Follow-Up 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
 Shockwave Medical Coronary IVL Procedure 
A full description of the procedure is detailed in the Instructions for Use (IFU). The 
appropriately sized IVL balloon catheter was selected per the IFU.  Once the IVL balloon 
was placed in the target lesion area, the balloon was inflated to 4 ATM and IVL treatment 
delivered for the pre-programmed time of 10 seconds to deliver 10 pulses.  Note that the 
generator was programmed to force a minimum pause time of 10 seconds following every 10 
pulses delivered.  Following the IVL treatment, the balloon was inflated to the reference size 
using the balloon compliance chart (refer to IFU) and the lesion response was recorded on 
fluoroscopy.  The balloon was deflated and the physician waited 30 seconds to re-establish 
blood flow.  The steps above were repeated to complete a minimum single treatment with 20 
pulses.  If additional lesion areas needed to be treated, the treatment steps as identified above 
and per the IFU were repeated.  The pulse maximum for each catheter was 80 pulses. If more 
pulses were needed, an additional catheter was used.  
If the Investigator was able to pass a guidewire but was unable to pass the IVL balloon 
catheter across the lesion, then an adjunctive tool (i.e. 1.5 mm PTCA balloon, Guide Liner 
guide extension catheter, or buddy wire) was used prior to re-insertion of the IVL Coronary 
Balloon. The eligible lesion was then treated directly per the IFU with the IVL device.  
The residual stenosis was assessed by the physician following the IVL procedure.  The IVL 
procedure was considered successful if the residual stenosis was <50% by visual estimate, as 
determined by the Investigator, prior to stent placement. If the residual stenosis was >50%, a 
non-compliant balloon was used to dilate the lesion prior to stenting.  This information was 
recorded in the case report form.   
The stent was delivered using a standard approach. If needed, the stent was post-dilated using 
PTCA balloons.  Following delivery of the coronary stent, angiography was performed to 
determine the final residual stenosis.  
Use of intravascular imaging, including optical coherence tomography (OCT), was allowed 
per standard of care as clinically needed. 
 
 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
4 LIST OF REFERENCES  
 
1 Lee M et al.  The impact and pathophysiologic consequences of coronary artery calcium 
deposition in percutaneous coronary interventions.  J Invasive Cardiol 2016; 28(4): 160-167. 
2 Bhatt P, Parikh P, Patel A, et al.  Orbital atherectomy system in treating calcified coronary 
lesions: 3-Year follow-up in first human use study (ORBIT I trial).  Cardiovasc Revasc Med  
2014; 15:204–208. 
3 Mori S, Yasuda S, Kataoka Y, Morii I, Kawamura A, Miyazaki S. Significant association of 
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4 Wiemer M, Butz T, Schmidt W, Schmitz KP, Horstkotte D, Langer C. Scanning electron 
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5 Kini AS, Vengrenyuk Y, Pena J, et al. Optical coherence tomography assessment of the 
mechanistic effects of rotational and orbital atherectomy in severely calcified coronary lesions. 
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6 Karimi Galougahi K, Shlofmitz RA, Ben-Yehuda O, et al. Guiding Light: Insights Into 
Atherectomy by Optical Coherence Tomography. JACC Cardiovasc Interv 2016;9:2362-3.  
7 Abdel-Wahab M, Richardt G, Joachim Buttner H, et al. High-speed rotational atherectomy 
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randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex 
Native Coronary Artery Disease) trial. JACC Cardiovasc Interv 2013;6:10-9. 
8 Iwasaki K, Samukawa M, Furukawa H. Comparison of the effects of nicorandil versus 
verapamil on the incidence of slow flow/no reflow during rotational atherectomy. Am J 
Cardiol 2006;98:1354-6. 
9 Matsuo H, Watanabe S, Watanabe T, et al. Prevention of no-reflow/slow-flow phenomenon 
during rotational atherectomy--a prospective randomized study comparing intracoronary 
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10 Sakakura K, Ako J, Wada H, et al. Beta-blocker use is not associated with slow flow during 
rotational atherectomy. J Invasive Cardiol 2012;24:379-84. 
11 Sakakura K, Ako J, Wada H, et al. Comparison of frequency of complications with on-label 
versus off-label use of rotational atherectomy. Am J Cardiol 2012;110:498-501. 
12 Chambers J, Feldman R, et al. Pivotal Trial to Evaluate the Safety and Efficacy of the Orbital 
Atherectomy System in Treating De Novo, Severely Calcified Coronary Lesions (ORBIT II). J 
Am Coll Cariol Intv 2014; 7: 510-8. 
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Götberg M, Whitbourn R, Van Mieghem N, Meredith IT, Di Mario C, Fajadet J. Optical 

 
Disrupt CAD II Protocol Synopsis 
NCT03328949 
 
Confidential –This document is property of Shockwave Medical, Inc. 
 
 
Coherence Tomography Characterization of Coronary Lithoplasty for Treatment of Calcified 
Lesions: First Description. JACC Cardiovasc Imaging. 2017 Aug;10(8):897-906.