New Enrollment Post Approval Registry for the Shockwave Intravascular Lithotripsy (IVL) System With Shockwave C2 Coronary Intravascular Lithotripsy (IVL) Catheter
Conditions: Coronary Artery Disease, Myocardial Infarction
Sponsor: Shockwave Medical, Inc.

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
Study Title: New Enrollment Post Approval Registry for the Shockwave Intravascular Lithotripsy 
(IVL) System with Shockwave C2 Coronary Intravascular Lithotripsy (IVL) Catheter (Disrupt 
CAD III PAS Study) 
 
NCT Number:  NCT05021757 
 
Protocol Date: May 4, 2021 
 
Revision: B 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
Investigational 
Plan/Study/Protocol 
Number:  
Disrupt CAD III PAS Study – CP 64647 
Study Title: 
New Enrollment Post Approval Registry for the Shockwave 
Intravascular Lithotripsy (IVL) System with Shockwave C2 Coronary IVL 
Catheter 
Study Objective:  
The objective of this Post Approval Registry is to better understand the 
utilization, safety, and effectiveness of the Shockwave Coronary IVL 
System in a ”real-world” setting. 
Study Devices: 
Shockwave IVL System with Shockwave C2 Coronary IVL Catheter 
Indications for Use:  
The Shockwave IVL System with Shockwave C2 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, observational, single-arm post-approval study 
using data collected in the National Cardiovascular Data Registry 
(NCDR®) CathPCI Registry®.  
Enrollment/ 
Number of Sites: 
Approximately 1000 patients in the CathPCI Registry® (including a 
minimum of 30 patients with permanent pacemakers [PPM] or 
implantable cardioverter defibrillators [ICDs]) will be enrolled. 
Subject Population: 
Patients with severely calcified, stenotic de novo coronary artery 
lesions presenting with stable, unstable, or silent ischemia that are 
suitable for percutaneous coronary intervention (PCI) and with clinical 
characteristics similar to the Disrupt CAD III IDE study (IDE G180146). 
Study Duration / 
Follow-Up Period:  
Subjects will be followed through discharge. A minimum of 150 patients 
will be followed 30 days post-procedure. 
Safety Endpoints: 
Mortality and procedure-related adverse events 
IVL-specific data reporting 
• 
IVL-related ventricular arrhythmia 
• 
IVL balloon loss of pressure and related serious dissections  
• 
Safety of IVL in patients with PPM/ICD 
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. Left ventricular ejection fraction >25% within 6 months  
4. The target lesion must be a de novo coronary lesion that has not 
been previously treated with any interventional procedure 
5. LAD, RCA or LCX (or of their branches) with: 
• 
Stenosis of ≥70% and <100% or  

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
• 
Stenosis ≥50% and <99% (visually assessed) with evidence of 
ischemia via positive stress test, or fractional flow reserve 
(FFR) value ≤0.80, or iFR <0.90 or IVUS or OCT minimum 
lumen area ≤4.0 mm² 
6. The lesion length must not exceed 40 mm 
7. The target vessel must have TIMI flow 3 at baseline (visually 
assessed; may be assessed after pre-dilatation) 
8. Evidence of calcification at the lesion site by 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  
Exclusion Criteria: 
1. Subject experienced an acute MI (STEMI or non-STEMI) within 30 
days prior to index procedure  
2. New York Heart Association (NYHA) class III or IV heart failure 
3. Renal failure with serum creatinine >2.5 mg/dL or chronic dialysis 
4. Subjects in cardiogenic shock or with clinical evidence of acute 
heart failure 
5. Target lesion is located in a native vessel that can only be 
reached by going through a saphenous vein or arterial bypass 
graft 
6. Previous stent within target lesion (in-stent restenosis) 
Statistical Methods: 
Interim results and final results will be analyzed using descriptive 
statistics; there is no formal hypothesis testing for the PAS.  
Sponsor: 
Shockwave Medical, Inc. 
5403 Betsy Ross Drive 
Santa Clara, CA 95054 
USA 
 
 
 
 
 
 
 
 
 
 
 

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
1.0 
INTRODUCTION/BACKGROUND 
1.1 Disrupt CAD III IDE Study  
The objective of the Disrupt CAD III investigational device exemption (IDE) study was to 
assess the safety and effectiveness of the Shockwave Intravascular Lithotripsy (IVL) 
System with Shockwave C2 Coronary Intravascular Lithotripsy (IVL) Catheter, hereafter 
referenced as the Shockwave Coronary IVL System, to treat de novo, calcified, stenotic, 
coronary lesions prior to stenting against objective performance goals.  
A total of 431 subjects (47 roll-in, 384 pivotal) were enrolled from 47 centers in the United 
States, France, Germany and the UK. Enrollment began in January 2019 and was 
completed in March 2020. The primary safety endpoint was freedom from major adverse 
cardiac events (MACE) through 30 days and the primary effectiveness endpoint of 
Procedural Success (defined as stent delivery with a residual stenosis < 50% without in-
hospital MACE) was evaluated at discharge. The Pivotal Analysis Set (n=384) was the 
primary analysis cohort used to assess the primary safety and effectiveness endpoints. 
The study met its primary safety endpoint. The observed freedom from 30-day MACE was 
92.2% (353/383) and the lower bound of the one-sided 95% confidence interval was 89.9%, 
greater than the performance goal of 84.4%. As such, the null hypothesis was rejected, and 
the primary safety endpoint was met (p<0.0001).  The study also met its primary 
effectiveness endpoint. The observed rate of Procedural Success was 92.4% (355/384) and 
the lower bound of the one-sided 95% confidence interval was 90.2%, greater than the 
performance goal of 83.4%. As such, the null hypothesis was rejected, and the primary 
effectiveness endpoint was met (p<0.0001). 
On February 12, 2021, the Shockwave Coronary IVL System was granted FDA approval. 
As part of the FDA Conditions of Approval, Shockwave Medical is conducting a Post 
Approval Registry leveraging the ACC NCDR® CathPCI Registry®.  Established registries 
like the CathPCI Registry® are an efficient way to collect objective clinical endpoint data on 
large, real-world populations from a broad spectrum of institutions. 
1.2 NCDR® CathPCI Registry® 
Developed in 1997 by the American College of Cardiology (ACC), the NCDR® was created 
as an exploration into strategies for improving cardiovascular care through the use and 
application of clinical data. Today, the NCDR® is a reputable and dependable quality 
improvement resource that continues to evolve to meet the demands of the changing health 
care environment. 
Currently, the NCDR® suite of cardiovascular data registries covers several clinical areas 
including acute myocardial infarction (MI) treatment, diagnostic cardiac catheterization and 
percutaneous coronary intervention (PCI), and transcatheter valve therapy procedures. 

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
The CathPCI Registry® assesses the characteristics, treatments and outcomes of cardiac 
disease patients who receive diagnostic catheterization and/or PCI procedures. The tool 
captures the data that measure adherence to ACC/AHA clinical practice guideline 
recommendations, procedure performance standards and appropriate use criteria (AUC) 
for coronary revascularization.  Over 1700 institutions currently participate in the CathPCI 
Registry®, representing over 95% of US centers performing PCI procedures. Data on over 
750,000 patients undergoing PCI are collected annually. The CathPCI Registry® is 
approved as non-exempt human subject research under 45 CFR 46 Subpart A with a waiver 
of informed consent. 
1.3 Study Rationale 
The Coronary IVL New Enrollment Post Approval Registry is being conducted to better 
understand the utilization, safety, and effectiveness of the Shockwave Coronary IVL System 
in a ”real-world” setting following FDA approval. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
2.0 
DATA COLLECTION AND ANALYSIS 
2.1 Data Collection Forms 
Hospitals enter information from PCI procedures using an online form based on the CathPCI 
Registry® Data Collection Form. All data in the registry is site-reported; there is no independent 
adjudication of adverse events or core lab assessment of angiographic characteristics. 
The CathPCI Registry® data collection form will be used for this study and captures information 
on each PCI case including:  
• 
Demographics 
• 
History and Risk Factors 
• 
Pre-Procedure information (diagnostics, medications) 
• 
Procedural details 
o Concomitant procedures 
o Target lesion characteristics (site-reported) 
o Devices used 
o Post-intervention stenosis (site-reported) 
• 
Intra and post-procedure adverse events 
• 
Discharge information 
• 
Follow-up information at 30 days (adverse events, medications) (for sites that have 
opted in to report data beyond discharge)  
Observational information on IVL-specific data will be collected on a separate IVL Addendum 
developed by ACC to support the PAS.  The IVL Addendum form captures procedural 
information including: 
• 
Ventricular arrhythmias during IVL pulses 
• 
IVL balloon loss pressure or burst/rupture 
• 
Serious dissections related to IVL burst/rupture 
• 
Inappropriate ICD shocks during delivery of IVL pulses 
• 
Adverse interactions between IVL and the PPM 
2.2 Data Processing 
The ACC will provide quarterly reports to Shockwave on procedures in the CathPCI Registry® 
where a Shockwave C2 Coronary IVL catheter was used.  The reports will include all fields 
contained in the Data Collection form and all fields in the IVL Addendum.   
Shockwave will filter the data to identify patients with clinical characteristics similar to the 
population studied in the Disrupt CAD III study using the eligibility criteria outlined above.   
 
 
 

 
DISRUPT CAD III POST-APPROVAL STUDY (PAS) PROTOCOL SYNOPSIS 
NCT05021757 
 
Confidential – This document is property of Shockwave Medical, Inc. 
2.3 Data Integrity 
To ensure the validity of this dataset, the registries within the NCDR® employ a multipronged 
approach to ensure that high quality data are captured by the participating facilities as follows: 
(1) National audit program, (2) data quality checks and system alerts, (3) trained data capture 
personnel, (4) data capture software rules, and (5) data dictionary development. 
1. National Audit Program 
Each registry within the NCDR® has a data audit conducted annually. Facilities are 
randomly selected for participation in the audit, which compares the medical record data 
provided to the auditor by the facility against the data collected in the registry.  
2. Data Quality Checks and System Alerts 
Patient data are entered directly and securely to the registries through a web-based data 
collection tool. The Data Quality Check function provides real-time alerts that identify 
out-of-range errors and incomplete data so that participants may return to the relevant 
fields and correct/complete them. 
Prior to any large-scale analysis of any registry data, a number of additional range and 
logic checks will be conducted to ensure data completeness and validity. 
3. Trained Data Collection Personnel 
Facilities participating in the NCDR® may employ varied personnel for data capture and 
entry. Physicians provide clinical and programmatic oversight and each facility has an 
assigned Registry Site Manager (RSM) to oversee data collection and registry reporting.  
4. Data Capture Software Rules 
The NCDR® provides participating facilities a web-based tool to capture patient data that 
conforms to clinical and technical specifications for core elements, definitions, coding, 
editing, transmission, and encryption protocols. The rigor of these technical 
specifications explicitly impacts the quality of data captured by employing a series of 
rules that create a uniform platform for data to be collected across multiple facilities.  
5. Data Dictionary Development 
The selection of registry data elements are based on input from clinical experts, 
regulatory agencies, and industry. These evidence-based elements are intended to 
measure clinical practice and patient outcomes for each patient, as well as identify 
patterns of clinical care and facilitate risk judgment.  
2.4 Statistical Analysis 
Interim results and final results will be analyzed using descriptive statistics; there is no formal 
hypothesis testing for the PAS.  The sample size of 1000 is sufficient to accommodate 
approximately 30 PPM/ICD patients.