Prospective, Multicenter, Single-Arm Study of the SWM-1234 in Calcified Coronary Arteries (Disrupt CAD IV Study - Japan)
Phase: NA
Conditions: Coronary Artery Disease, Myocardial Infarction
Sponsor: Shockwave Medical, Inc.

 
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Study Title: Prospective, Multicenter, Single-Arm Study of the SWM-1234 in Calcified Coronary 
Arteries (Disrupt CAD IV Study-Japan) 
 
NCT Number:  NCT 04151628 
 
Protocol Date: June 19, 2019 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

 
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Study Title: 
Prospective, Multicenter, Single-Arm Study of the SWM-1234 in Calcified 
Coronary Arteries (Disrupt CAD IV Study - Japan) 
Study Objective:  
The objective of this study is to assess the safety and effectiveness of 
SWM-1234 to treat de novo, calcified, stenotic, coronary lesions prior to 
stenting. 
Study Design: 
Prospective, multicenter, single-arm study 
Number of sites/ 
Sample Size 
The study will be conducted at up to 8 sites in Japan. It is anticipated that 
up to 64 subjects will be enrolled in the SWM-1234 study, in addition to 8 
roll-in subjects (1 per study site).  
Subject Population: 
The study will enroll subjects with de novo, calcified coronary artery 
lesions presenting with stable, unstable or silent ischemia that are 
suitable for percutaneous coronary intervention (PCI). All potential 
subjects must complete the consent process prior to undergoing any 
trial specific procedures and evaluations.  
Study Duration / 
Follow-Up Period:  
Enrollment duration: approximately 7 months 
Study duration: approximately 3 years 
Subjects will be followed through discharge, 30 days, 6, 12 and 24 months 
OCT/OFDI Sub-
study 
An Optical Coherence Tomography (OCT) / Optical frequency domain 
imaging (OFDI) sub-study will be conducted on all subjects. The 
objective is to further understand the mechanism of action of SWM-
1234 for the treatment of de novo, calcified, stenotic, coronary lesions 
prior to stenting. OCT or OFDI imaging will be completed at three time-
points during the index procedure.  
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) defined as CK-MB level > 3 times the 
upper limit of lab normal (ULN) value with or without new 
pathologic Q wave at discharge (periprocedural MI) and using the 
Fourth Universal Definition of Myocardial Infarction beyond 
discharge (spontaneous MI); or 
• 
Target Vessel Revascularization (TVR) defined as 
revascularization at the 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 
<50% (core laboratory assessed) and without in-hospital MACE. 

 
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Secondary 
Endpoints: 
• 
Device Crossing Success is defined as the ability to deliver the SWM-
1234 catheter across the target lesion, and delivery of lithotripsy 
without serious angiographic complications immediately after 
treatment.  
• 
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 
<30% (core laboratory assessed) and without in-hospital MACE. 
• 
Angiographic Success defined as stent delivery with ≤30% residual 
stenosis and 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. 
• 
MACE at 6, 12 and 24 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 and 24 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).  
• 
Sensitivity analyses will be reported for MI using the Fourth Universal 
definition of MI and the Society for Cardiovascular Angiography and 
Interventions (SCAI) definitions at 30 days, 6, 12 and 24 months. 
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. 
a. 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). 

 
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b. 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  
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: 
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) 

 
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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 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.  
  
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 

 
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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 ≥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. Unprotected left main diameter stenosis >30% 
25. Target vessel is excessively tortuous defined as the presence of 
two or more bends >90º or three or more bends >75º 
26. Definite or possible thrombus (by angiography or intravascular 
imaging) in the target vessel 
27. Evidence of aneurysm in target vessel within 10 mm of the target 
lesion 
28. Target lesion is an ostial location (LAD, LCX, or RCA, within 5 mm 
of ostium) or an unprotected left main lesion 
29. Target lesion is a bifurcation with ostial diameter stenosis ≥30% 

 
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30. Second lesion with >50% stenosis in the same target vessel as the 
target lesion including its side branches 
31. Target lesion is located in a native vessel that can only be reached  
by going through a saphenous vein or arterial bypass graft 
32. Previous stent within the target vessel implanted within the last 
year 
33. Previous stent within 10 mm of the target lesion regardless of the 
timing of its implantation 
34. Angiographic evidence of a dissection in the target vessel at 
baseline or after guidewire passage 
Statistical Methods: An Investigational Device Exemption (IDE G180146) study called Disrupt 
CAD III will enroll 392 subjects at 50 US and European sites. The Disrupt 
CAD III population is intended to support the US FDA approval.  
The primary safety and effectiveness endpoints in this CAD IV study will 
be compared to a similar set of subjects from the CAD III study using a 
propensity-score matched analysis. To maximize power and take 
advantage of the larger CAD III study, 1:5 matching will be done.  
 
Primary Safety Endpoint:  
Safety will be assessed by freedom from major adverse cardiac events 
(MACE) within 30 days of the index procedure. 
Statistical Hypothesis: 
• 
H0: πS CAD IV ≤ πS CAD III - δ 
• 
HA: πS CAD IV > πS CAD III - δ 
• 
πS CAD IV = 30-day freedom from MACE in CAD IV 
• 
πS CAD III = 30-day freedom from MACE in CAD III 
• 
δ = Margin of non-inferiority, 9.36% 
• 
Expected 30-day freedom from MACE in CAD IV = 89.6% 
• 
Expected 30-day freedom from MACE in CAD III = 89.6% 
• 
Statistical significance: one-sided α = 0.1 
• 
1:5 matching (CAD IV: CAD III) 
Based on the above assumptions 60 evaluable CAD IV subjects will be 
needed to achieve a statistical power of 72%. To account for a possible 
5% attrition rate, 64 subjects will be enrolled. 
Primary Effectiveness Endpoint:  

 
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Procedural Success defined as stent delivery with a residual stenosis 
<50% and without in-hospital MACE.  
Statistical Hypothesis: 
• 
H0: πe CAD IV ≤ πe CAD III - δ 
• 
HA: πe CAD IV > πe CAD III - δ 
• 
πe CAD IV = Procedure success rate in CAD IV 
• 
πe CAD III = Procedure success rate in CAD III 
• 
δ = Margin of non-inferiority, 10.0% 
• 
Expected 30-day Procedure Success in CAD IV = 88.9% 
• 
Expected 30-day Procedure Success in CAD III = 88.9% 
• 
Statistical significance: one-sided α = 0.1 
• 
1:5 matching (CAD IV: CAD III) 
Based on the above assumptions 60 evaluable CAD IV subjects will be 
needed to achieve a statistical power of 75%. To account for a possible 
5% attrition rate, 64 subjects will be enrolled.  
 
Sponsor: 
Shockwave Medical, Inc. 
5403 Betsy Ross Drive 
Santa Clara, CA 95054 
USA 

 
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1.0 
 INTRODUCTION/BACKGROUND 
1.1 Calcified Coronary Lesions  
Calcified coronary lesions are associated with advanced age, diabetes and chronic 
kidney disease.(1)   Approximately 38% and 73% of all 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)   
Coronary artery calcification impacts interventional outcomes by adversely affecting 
stent delivery(3), damaging the drug-eluting polymer(4) and impairing stent expansion 
and apposition.(5) 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; in concentric calcium, the 
pressure-generated force may be insufficient for 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, rates of 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 nine months, rotational atherectomy (RA) had similar 
rates of binary restenosis, target lesion revascularization (TLR), stent thrombosis and 
 
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 coronary artery calcification in stent 
  delivery route with restenosis after sirolimus-eluting stent implantation. Circ J 2009; 73:1856-63. 
4 Wiemer M, Butz T, Schmidt W, Schmitz KP, Horstkotte D, Langer C. Scanning electron microscopic analysis of different drug 
  eluting stents after failed implantation: from nearly undamaged to major damaged polymers. Catheter Cardiovasc Interv 2010:75: 
  905-911. 
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. Catheter Cardiovasc Interv 2015;86:1024-32. 
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 before paclitaxel-eluting stent 
  implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent 
  Treatment for Complex Native Coronary Artery Disease) trial. JACC Cardiovasc Interv 2013;6:10-19. 
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 continuous infusion of verapamil and nicorandil. Am Heart J 
   2007;154:994.e1-6. 
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. 
 

 
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MACE, despite a higher procedural acute gain over percutaneous transluminal coronary 
angioplasty PTCA. (7)  Chambers et al. reported the 30-day orbital atherectomy (OA) 
results from the ORBIT II Study.  Orbital atherectomy 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%, 
respectively, while in-hospital non-Q wave MIs occurred in 8.6% of the subjects.( 12) 
1.2 Coronary Intravascular Lithotripsy 
The completed Disrupt CAD I Study conducted by Shockwave Medical Inc. reported the 
safety and performance of coronary intravascular lithotripsy (IVL) in vessel preparation 
for de novo, calcified, stenotic, coronary lesions prior to stent implantation in 60 subjects 
followed for six months. Successful delivery of the IVL catheter 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 patients suffering cardiac 
death.  Results of the optical coherence tomography (OCT) sub-study (n=31) identified 
modification with fracture as a major mechanism of action of IVL in vivo and 
demonstrated effectiveness in the achievement of significant acute area gain and 
enabled stent apposition and expansion.(13) 
The Disrupt CAD II study was a post-market clinical follow-up trial designed to evaluate 
the safety and performance of the Shockwave Coronary Intravascular Lithotripsy 
System using real world data. The study was conducted at 15 sites in Europe with up to 
120 subjects. Subjects were followed for 30 days post procedure and the primary safety 
endpoint was in-hospital major adverse cardiac events (MACE). Enrollment in the 
Disrupt CAD II study started in May 2018.  
1.3 Study Rationale 
Disrupt CAD IV is a single arm study enrolling Japanese subjects with similar inclusion 
and exclusion criteria to the Disrupt CAD III IDE study. The primary safety and 
effectiveness endpoints in CAD IV will be compared to a similar set of subjects from the 
CAD III study using a propensity-score matched analysis. To maximize power and take 
advantage of the larger CAD III study, 1:5 matching will be done. Non-inferiority of CAD 
IV primary safety and effectiveness endpoints to CAD III will be assessed. The rationale 
for this global IDE study is to assess the safety and effectiveness of the Shockwave 
Coronary IVL System with up to 24 months of follow-up.   
 
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 Cardiol Intv 2014; 7: 510-518. 
13 Ali ZA, Brinton TJ, Hill JM, Maehara A, Matsumura M, Karimi Galougahi K, Illindala U, Götberg M, Whitbourn R, Van Mieghem N, 
    Meredith IT, Di Mario C, Fajadet J. Optical Coherence Tomography Characterization of Coronary Lithoplasty for Treatment of 
    Calcified Lesions: First Description. JACC Cardiovasc Imaging. 2017 Aug;10(8):897-906. 

 
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2.0 
Study Device Description   
The study device being evaluated is SWM-1234.  
2.1 Study Device System 
SWM-1234 is a proprietary 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 system consists of an IVL Catheter with two lithotripsy 
emitters enclosed within an integrated balloon, an IVL Generator, IVL Connector Cable, 
and related accessories.  
The IVL 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  sonic pressure waves 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 C² IVL Catheter is available in 4 sizes: 2.5 mm,  3.0 mm, 3.5 mm, and 4.0 mm 
diameter, and are all 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 
IVL Catheter has compatibility with guide catheters as specified in the Instructions for 
Use (IFU).  The IVL 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 IVL Generator is used to support all sizes of IVL Catheters and the software can 
detect the different IVL Catheter types and sizes through a unique PCB incorporated 
inside the IVL Catheter.  The IVL Connector Cable connects the IVL Generator to the 
IVL Catheter and includes a remote actuator used to activate the energy delivery from 
the IVL Generator to the IVL Catheter.  The IVL Catheter is used exclusively with the 
Shockwave IVL Generator and IVL Connector Cable.  
 
The IVL 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 IVL Generator and IVL 
Connector Cable are non-sterile and reusable. 
 
2.2 Indication for Use 
The SWM-1234 is an investigational device that is not currently commercially available 
in Japan. 
The SWM-1234 is indicated to facilitate coronary intervention by removal of calcified de 
novo coronary artery lesions 

 
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3.0 
STATISTICAL CONSIDERATIONS 
3.1  Evaluation of Primary Endpoints  
CAD IV will be single arm study enrolling Japanese subjects with similar inclusion and exclusion 
criteria to the Disrupt CAD III IDE study. The primary safety and effectiveness endpoints in CAD 
IV will be compared to a similar set of subjects from the CAD III study using a propensity-score 
matched analysis. To maximize power and take advantage of the larger CAD III study, 1:5 
matching will be done.  
Primary Safety Endpoint: 
Safety will be assessed by freedom from major adverse cardiac events (MACE) within 30 days 
of the procedure. MACE is defined as the composite occurrence of:  
• 
Cardiac death; or 
• 
Myocardial Infarction (MI)- defined as CK-MB level > 3 times the upper limit of lab 
normal (ULN) value with or without new pathologic Q wave at discharge (periprocedural 
MI) and using the Fourth Universal Definition of Myocardial Infarction beyond discharge 
(spontaneous MI); or 
• 
Target vessel revascularization-defined as revascularization at the target vessel 
(inclusive of the target lesion) after the completion of the index procedure  
For the primary safety endpoint, the non-inferiority of CAD IV freedom from MACE to CAD III 
freedom from MACE within 30 days of the procedure will be assessed. Specifically, the null and 
alternative hypotheses are listed below.  
 
Statistical Hypothesis:  
• H0: πS CAD IV ≤ πS CAD III - δ  
• HA: πS CAD IV > πS CAD III - δ  
• πS CAD IV = 30-day freedom from MACE in CAD IV  
• πS CAD III = 30-day freedom from MACE in CAD III  
• δ = Margin of non-inferiority, 9.36%  
• Expected 30-day freedom from MACE in CAD IV = 89.6%  
• Expected 30-day freedom from MACE in CAD III = 89.6%  
• Statistical significance: one-sided α = 0.1  
• 1:5 matching (CAD IV : CAD III)  
• Based on the above assumptions 60 evaluable CAD IV subjects will be needed to achieve a 
statistical power of 72%. To account for a possible 5% attrition rate, 64 subjects will be enrolled.  
 
 
 

 
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Primary Effectiveness Endpoint: 
Procedural Success defined as stent delivery with a residual stenosis <50% (by angiographic 
core laboratory analysis) and without in-hospital MACE.  
For the primary effectiveness endpoint, the non-inferiority of CAD IV procedural success to CAD 
III procedural success will be assessed. For the primary effectiveness endpoint, the null and 
alternative hypotheses are listed below.  
 
Statistical Hypothesis:  
• H0: πe CAD IV ≤ πe CAD III - δ  
• HA: πe CAD IV > πe CAD III - δ  
• πe CAD IV = Procedure success rate in CAD IV  
• πe CAD III = Procedure success rate in CAD III  
• δ = Margin of non-inferiority, 10.0%  
• Expected 30-day Procedure Success in CAD IV = 88.9%  
• Expected 30-day Procedure Success in CAD III = 88.9%  
• Statistical significance: one-sided α = 0.1  
• 1:5 matching (CAD IV: CAD III)  
• Based on the above assumptions 60 evaluable CAD IV subjects will be needed to achieve a 
statistical power of 75%. To account for a possible 5% attrition rate, 64 subjects will be enrolled.  
 
3.2  Populations for Analyses 
The primary analysis dataset for all study outcomes will be the intent-to-treat (ITT) population 
wherein data from all enrolled subjects will be analyzed.  
Study outcomes will also be analyzed using a per-protocol (PP) population.  The PP population 
includes all subjects who had no pre-specified inclusion and exclusion violations and were 
treated with IVL therapy.  
3.3  Analysis Strategy 
 
General Approach 
Continuous variables will be summarized using the mean, standard deviation (SD), median, first 
and third quartiles, minimum, and maximum. Categorical data will be summarized as a 
frequency and percentage. The number of events, Kaplan-Meier estimated event rates, and log-
rank test will summarize time to event data greater than 30 days.  
 
Analysis of Primary Endpoints 
 
For the primary safety endpoint analysis, the non-inferiority of CAD IV freedom from MACE rate 
at 30 days to CAD III freedom from MACE rate at 30 days will be assessed using the 

 
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Farrington-Manning test of non-inferiority for two binomial proportions with a non-inferiority 
margin of δ = 9.36% at the 0.1 level of significance (one-sided).  
Propensity score matching will identify a covariate-unbiased population of subjects between the 
CAD IV and CAD III populations. To maximize power and take advantage of the larger CAD III 
study, 1:5 matching will be done.  
A logistic regression will be used to model the likelihood of study enrollment in CAD IV versus 
CAD III as a function of the baseline characteristics. The covariates are chosen a priori based 
on their suspected relationship to MACE, possible relationship to study, and the ability to obtain 
comparable values from the two trials. The full list of baseline characteristics is present below.  
 
• Age (at enrollment)  
• Gender (male vs female)  
• Site geography (US vs outside of US)  
• Diabetes mellitus (medically treated)  
• Prior CABG  
• Estimated glomerular filtration rate (eGFR)  
• Reference vessel diameter (angiographic core lab assessed)  
• Lesion length (angiographic core lab assessed)  
• Bifurcated lesions (angiographic core lab assessed)  
 
Every CAD IV patient will be matched with up to 5 of the closest CAD III patients based on the 
absolute difference in propensity scores. Unmatched patients will be excluded from the primary 
analysis. Finally, the proportion of freedom from MACE at 30-days along with the corresponding 
exact 95% CIs will be presented for the CAD IV group and the matched CAD III group. 
Farrington-Manning one-sided p-value and lower bound of the one-sided 90% CI of the 
difference in proportion between matched CAD III and CAD IV groups will be presented.  
Similar to the primary safety endpoint, for the primary effectiveness endpoint analysis, the non-
inferiority of CAD IV procedure success to CAD III procedure success will be assessed using the 
Farrington-Manning test of non-inferiority for two binomial proportions with a non-inferiority margin 
of δ = 10.0% at the 0.1 level of significance (one-sided). Comparison between the two studies will 
be performed on the same set of propensity-score matched subjects as in the primary safety 
analysis. 
In addition to the analysis of primary endpoints, all comprehensive Disrupt CAD IV results will be 
reported to assess CAD IV as a standalone study as well. 
 
3.4  Analysis of Secondary Endpoints 
Secondary endpoints will be presented as descriptive statistics. A description of each endpoint 
is summarized in this section.  
 
• 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  

 
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• 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 <30% (core laboratory 
assessed) and without in-hospital MACE  
• Angiographic Success defined as stent delivery with <30% residual stenosis and 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  
• MACE at 6, 12 and 24 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 and 24 months  
• At each time period: All death, cardiac death, MI, TV-MI, procedural and nonprocedural MI, ID-
TVR, ID-TLR, ID-non-TLR TVR, ID-non-TVR, all revascularizations (ID and non-ID), and stent 
thrombosis (ARC definite, probable, definite or probable)  
• Sensitivity analyses will be reported for MI using the Fourth Universal Definition of MI and the 
Society for Cardiovascular Angiography and Interventions (SCAI) definitions at 30 days, 6, 12 
and 24 months  
 

 
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4.0 
 Schedule of Evaluations 
Table 1 lists the schedule of evaluations required for this study. 
 
Table 1: Schedule of Evaluations 
Assessment 
Screening/ 
Baseline1 
(Day -14 to Day 0) 
Enrollment
/ Procedure 
(Day 0) 
12-24 hours 
post-procedure, 
or at discharge2  
30 Days 
(±7 days) 
6, 12, 24 
Months 
(±30 days) 
Informed Consent 
X 
 
 
 
 
Medical History  
X 
 
 
 
 
Physical Examination/Vital Signs 
X 
 
 
 
NYHA Classification 
X 
 
 
 
 
Canadian Cardiovascular Society 
(CCS) Angina Classification 
X 
 
 
X 
X 
Laboratory Assessments 
Platelet count, 
creatinine, 
hemoglobin 
CK-MB3,  
troponin4  
CK-MB3, 
troponin, 
creatinine, 
hemoglobin 
 
 
Urine/serum pregnancy test is 
required for women of child-
bearing potential within 7 days prior 
to enrollment 
X 
 
 
 
 
LVEF (within 6-months of 
procedure) 
X5 
 
 
 
 
12-lead ECG 
X 
 
X 
 
Coagulation Studies: PT/PTT and 
INR (only required for patients who 
have taken warfarin within two 
weeks of enrollment) 
X 
 
 
 
 
Angiography 
 
X 
 
X6 
X6 
Sub-study: OCT/OFDI imaging  
 
 X 
 
 
 
Medication use 
X 
X 
X 
X 
X 
Adverse Event Assessment 
 
X 
X 
X 
X 
1 Screening/Baseline data collection can occur any time within 14 days of the procedure 
2 Laboratory assessments may be drawn at 12-24 hours post-procedure or at discharge, whichever is earlier, but at least 6 hours post procedure 
in patients with early discharge.  
3 For centers unable to perform the CK-MB assessment on-site, a blood sample must be drawn and sent to the central lab 
4 Patients presenting with stable angina may have biomarkers drawn from the side port of the sheath at the time of the procedure and the 
results do not need to be analyzed prior to enrollment.  
5 LVEF may be assessed during the baseline cardiac catheterization, prior to enrollment. 
6 If a revascularization procedure occurs during the follow-up period (planned or unplanned), angiographic images must be submitted to the 
core lab.  
 

 
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5.0 
Index Procedure 
5.1  Coronary Intravascular Lithotripsy Procedure 
 
 A full description of the procedure is detailed in the Instructions for Use (IFU). The appropriate 
sized SWM-1234 catheter should be selected per the IFU. A summary of the procedural steps is 
provided below. Angiographic images captured during the procedure will be sent to the core lab 
for analysis. 
 
• 
If the Investigator is able to pass a guidewire but is unable to pass the IVL Catheter across 
the lesion, an adjunctive tool (e.g., a GuideLiner or comparable guide extension catheter, 
+/- a buddy wire or buddy balloon) should be used prior to re-insertion of the IVL Catheter. 
The lesion will then be treated per the IFU with the IVL Catheter. If the IVL catheter will 
still not cross the lesion, the lesion may be pre-dilated with a 1.5 mm or occasionally 2.0 
mm PTCA balloon, after which the IVL catheter should be re-inserted.  
 
           Note: The subject is considered enrolled once the IVL Catheter has been inserted over a 
           0.014” guidewire which had previously passed across the study lesion. 
 
• 
If the Investigator is not able to cross the lesion with the IVL Catheter after exhausting 
adjunctive tools, this will be defined as a Device Delivery failure. Any further treatment will 
be done per standard care without the use of IVL. In the case of Device Delivery Failure, 
the patient is considered enrolled; as such, the subject should be followed per the 
Schedule of Evaluations and will be included in the intent-to-treat analysis.  
Note: To avoid Device Delivery Failures, the adjunctive tools noted above may be used 
before the IVL catheter is initially inserted.  
Note: Use of IVL is not permitted if non-conventional PTCA treatments, including 
atherectomy, laser or cutting/scoring balloons, were previously used to treat the lesion. 
 
• 
Once the IVL catheter is placed in the target lesion area, the balloon should be inflated to 
4 atm and IVL treatment delivered for the pre-programmed time of 10 seconds to deliver 
10 pulses.  
            Note: The IVL Generator is programmed to force a minimum pause time of 10 seconds 
            following every 10 pulses delivered.  
 
• 
Following IVL, inflate the balloon to the reference size using the balloon compliance chart 
(refer to IFU) and record lesion response on fluoroscopy.  
• 
Deflate the balloon to re-establish blood flow.  
• 
Repeat the steps above to complete a minimum single treatment with 20 pulses.  

 
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• 
If additional lesion area needs to be treated, follow the treatment steps identified above 
and per the IFU to ensure appropriate overlap between segments.  
 
          Note: The pulse maximum for each catheter is 80 pulses. If more pulses are needed, an  
         additional catheter must be used. The maximum number of pulses to treat a single arterial 
        segment is 80 pulses and therefore 160 pulses in an overlap segment. 
  
 
• 
The residual stenosis will be assessed by the physician following the IVL procedure. The 
IVL procedure is considered successful when the residual stenosis is <50%, by visual 
estimate, as determined by the Investigator prior to stent placement.  
• 
If the residual stenosis is >50% following IVL, a non-compliant balloon must be used to 
dilate the lesion prior to stenting. This information will be recorded in the case report form.  
• 
The stent will then be delivered using a standard approach.  
• 
Following stent implantation, post-dilatation with a non-compliant balloon with inflation 
pressure >=16 atm is mandatory.  
• 
Following delivery of the coronary stent and post-dilatation, angiography will be performed 
to determine the final residual stenosis for assessment of the primary effectiveness 
endpoint.  
• 
In addition, all subjects will be evaluated for life-threatening arrhythmias during the 
study. Baseline heart rhythm including the presence of baseline ectopy will be 
assessed. An assessment of ectopy and blood pressure in temporal association with 
IVL pulses will be recorded during the IVL procedure including any sustained ventricular 
tachycardia or fibrillation.  
 
 
5.2  Optical Coherence Tomography (OCT) Sub-study 
An OCT/Optical Frequency Domain Imaging (OFDI) sub-study will be conducted on all subjects. 
The objective is to further understand the mechanism of action ofSWM-1234 for the treatment of 
de novo, calcified, stenotic, coronary lesions prior to stenting. OCT or OFDI imaging will be 
completed at three time points: 1) pre-procedure, 2) immediately post-IVL treatment and 3) at 
the end of procedure following angiography. All OCT/OFDI images will be analyzed at the OCT 
core laboratory. OFDI or OCT may be used.