A Prospective Randomized Multicenter Trial Comparing Performance of Two Intracorporeal Lithotripters for Removal of Large Renal Calculi
Phase: NA
Conditions: Kidney Calculi
Sponsor: Indiana University

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Protocol Version 7.27.2020 
A Prospective Randomized Multicenter Trial Comparing Performance of Two 
Intracorporeal Lithotripters for Removal of Large Renal Calculi 
 
The ShockPulse-SE vs. Trilogy Trial 
 
 
 
 
CLINICAL INVESTIGATION PLAN 
 
 
Coordinating Principal 
Investigator 
Amy E. Krambeck, MD 
Michael O. Koch Professor of Urology 
Indiana University Health Physicians 
1801 N. Senate Boulevard, Suite 220 
Indianapolis, IN 46202 
 
Tel: 317-962-3700 
Email: akrambeck@iuhealth.org 
 
 

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Protocol Version 7.27.2020 
Protocol Synopsis 
A Prospective Randomized Multicenter Trial Comparing Performance of Two 
Intracorporeal Lithotripters for Removal of Large Renal Calculi - The 
ShockPulse-SE vs. Trilogy Trial 
Study 
Objective(s) 
To compare the performance, as measured by the stone clearance rate at 
time of percutaneous nephrolithotomy, of the ShockPulse-SE Lithotripsy 
System to the Trilogy Lithotrite. 
Study Devices 
1. ShockPulse-SE Lithotripsy System with the 3.76 mm probe 
2. Trilogy Lithotrite with 3.9 mm probe 
Indications for 
Use 
Both devices are cleared for use in the USA for the following indications: 
1. The ShockPulse-SE Lithotripsy System is intended to be used for 
fragmentation of urinary tract calculi in the kidney, ureter, and 
bladder. 
2. The Trilogy Lithotrite is intended to be used to fragment urinary 
tract calculi in the kidney, ureter, and bladder. 
Device Sizes 
1. Shock Pulse-SE 3.76 mm lithotripsy probe 
2. Trilogy 3.9 mm Probe 
Study Design 
Prospective, randomized, multicenter, 2 arm, comparative trial 
Planned Number 
of Subjects 
N=100 
 
Planned Number 
of 
Investigational 
Sites / Countries 
A total of 3 sites in the USA 
Primary 
Endpoint 
Stone clearance rate defined as the kidney stone surface area measured by 
pre-operative computed tomography (CT) scan divided by the time to 
remove the targeted stone burden.   
• Time to remove the targeted stone burden is measured at time the 
lithotripter unit starts fragmenting the stone to time all fragments 
are removed from the kidney based on visual inspection.  This is 
prior to final visual inspection of the kidney with a flexible 
nephroscope. 

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Protocol Version 7.27.2020 
Additional 
Endpoints 
Additional endpoints include the following: 
1. Device malfunctions 
2. All complications measured by the Clavien Classification of 
Surgical Complications 
3. Stone free status as defined by the presence or absence of stone 
material on postoperative CT imaging and at final follow up  
• Stone free status must be assessed postoperative day 1 by 
CT scan. 
Method of 
Assigning 
Patients to 
Treatment 
The patients will be block randomized 1:1 to either stone removal with the 
Trilogy or the ShockPulse –SE device. 
Follow-up 
Schedule 
1. Baseline (Clinic Visit) – within 3 months prior to surgical procedure 
2. Procedure (Hospital Visit) 
• Stone free status may be assessed at this time by CT scan on 
Postoperative day 1 
3. 6-12 Week Follow-up Visit (Clinic Visit) 
• Stone free status may be assessed at this time by KUB scan 
and/or ultrasound, or CT scan 
4. End of Study 
• End of study will be reached after completion of the 6-12 Weeks 
Follow-up Visit, subject withdrawal or lost to follow-up, 
whichever occurs first. 
Study Duration 
It is anticipated that this study will take 12 months to complete once IRB 
approval is obtained at all participating locations. 
 
 
 

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Key Inclusion 
Criteria 
1. ≥ 18 years of age 
2. Stone burden > 1.5 cm as measured on preoperative CT scan 
3. Patient is scheduled to undergo a percutaneous nephrolithotomy 
procedure 
4. Willing and able to provide informed consent 
Key Exclusion 
Criteria 
1. Pregnant 
2. Active urinary tract infection 
3. Prior shock wave lithotripsy within 3 months of study procedure 
4. Multiple percutaneous access sites are anticipated 
5. Unable or unwilling to provide informed consent 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
We hypothesize that the Trilogy will increase the stone clearance rate by 
25% compared to the Shockpulse-SE 
Statistical Test 
Method 
Outcomes between treatment groups will be assessed using a t-test to 
compare means.  Values of p<0.05 will be considered significant. 
Sample Size 
Parameters 
For simplicity, sample size calculations were performed using a two-sided 
Student t-test with a power of 90% and a significance level of alpha = 0.05.  
The primary outcome of interest is the clearance rate of the targeted stone 
burden.  Preliminary in vitro data shows a reduction of approximately 50% 
in the average lithotripter clearance time of a 1 cm3 BegoStone for the 
Trilogy lithotrite compared to the ShockPulse-SE.  Given the increased 
variability of use in vivo and across subjects, a more conservative 
difference was considered for sample size estimation.  Assuming a 25% 
improvement in clearance rate that results in an effect size of 0.7, a sample 
size of 44 subjects in each group is required. To account for the possibility 
of unevaluable data a total of 100 patients, 50 in each group will be 
enrolled. 
 
 

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Protocol Version 7.27.2020 
Introduction 
Large and complex renal calculi, defined as those with a maximum diameter of ≥ 1.5 cm, can be 
removed from the upper urinary tract by percutaneous nephrolithotomy but the stones usually require 
fragmentation in order to remove them through the access site.  There are a number of commercially 
available intracorporeal lithotripters used to fragment or break kidney stones to allow elimination 
including pneumatic, ultrasonic, and combination devices.  Each technology has its own relative 
advantages and disadvantages. 
New versions of intracorporeal lithotripter devices have been introduced with improvements meant to 
address prior functional limitations such as probe clogging or breaking and cumbersome hand piece 
design. 
 
The Trilogy lithotrite is the newest generation device stone fragmentation device from Boston Scientific. 
The Trilogy device uses unique technology to efficiently fragment and remove stone material, superior 
to other devices on the market based on preliminary bench testing.   From Olympus, the ShockPulse-SE 
Lithotripsy System (Cybersonics, Erie, PA, USA is a constant ultrasonic wave energy lithotripter with 
intermittent shock wave (ballistic/mechanical) energy.  The ShockPulse-SE has a single probe design with 
an OD of 3.76 mm which allows for larger sized stone fragments to be vacuumed from the urothelium.  
The larger, single lumen also allows for a high flow rate to reduce probe clogging events.  The end result 
is faster stone clearance rates based on in vitro studies (company brochure).2 
 
The objective of this study is to compare the performance, as measured by the stone clearance rate at 
time of percutaneous nephrolithotomy, of the ShockPulse-SE Lithotripsy System to the Trilogy lithotrite 
when used for large complex renal calculi. 
2. Device Description 
The Trilogy has been FDA cleared for fragmentation of urinary tract calculi in the kidney, ureter, and 
bladder.  Trilogy is a combined piezoelectric/pneumatic device capable of fragmenting calculi and 
aspirating stone debris.  The novel technology in Trilogy has been demonstrated in bench testing to 
more quickly disintegrate stones compared to other devices.  The following components are included in 
the Trilogy System: 
 
 

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Protocol Version 7.27.2020 
REF 
Description 
Trilogy Parts 
Trilogy Lithotrite 
M0068402010 
Swiss LithoClast® Trilogy Console 
M0068402030 
Swiss LithoClast® Trilogy Handpiece Kit 
M0068402050 
Swiss LithoClast® Trilogy Foot Switch  
M0068403590 
Trilogy Reusable Torque Wrench 
M0068401890 
Quick Guide 
M0068401810 
Stone Catcher Holder 
M0068401800 
HDMI-VDI cable (10m)  
M0068401820 
Filling Bottle 
M0068401830 
Bottle of Demineralized Water (2.5l) 
M0068401850 
Power Cord (US - 6m) 
M0068401860 
Swiss LithoClast® Trilogy System IFU  
M0068403540 
3.9mm x 350mm Trilogy Probe Kit  
M0068403550 
3.9mm x 440mm Trilogy Probe Kit  
M0068402980 
Stone Catcher for Trilogy 
 
The ShockPulse-SE Lithotripsy System has been FDA cleared fragmentation of urinary tract calculi in the 
kidney, ureter, and bladder.  The ShockPulse-SE System is an electromechanical device capable of 
fragmenting calculi and aspirating stone debris.  The novel technology in the ShockPulse-SE Lithotripsy 
System uses a single transducer and proprietary ShockPulse technology to generate both low-frequency 
mechanical impacts and high-frequency ultrasonic energy which quickly disintegrates stones.  The 
following components are included in the ShockPulse System: 
 
REF 
Description 
SPL-S 
ShockPulse-SE Lithotripsy System 
SPL-T 
ShockPulse Lithotripsy Transducer 
SPL-CSL 
ShockPulse Lithotripsy Cleaning Stylet - Large 
SPL-W 
ShockPulse Lithotripsy Wrench 
SPL-PC 
ShockPulse Lithotripsy Power Cord 
SPL-G 
ShockPulse Lithotripsy Generator 

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SPL-NC 
ShockPulse Lithotripsy Nose Cone 
SPL-IFU 
ShockPulse Lithotripsy Instructions for Use 
SPL-PDBX376 
ShockPulse Lithotripsy Probe, Sterile Single Use, 3.76 mm 
(3/Box) 
 
Study Objectives 
To compare the performance, as measured by the stone clearance rate at time of percutaneous 
nephrolithotomy, of the ShockPulse-SE Lithotripsy System to the Trilogy Lithotrite. 
Study Endpoints 
Primary Endpoint 
Stone clearance rate defined as the kidney stone surface area measured by preoperative computed 
tomography (CT) scan divided by the time to remove the targeted stone burden.  
 Time to remove the targeted stone burden is measured at time the lithotripter unit starts fragmenting 
the stone to time all fragments are removed from the kidney based on visual inspection.  This is prior to 
final visual inspection of the kidney with a flexible nephroscope. 
Additional Endpoints 
1. Device malfunctions 
2. All complications measured by the Clavien Classification of Surgical Complications 
Stone free status as defined by the presence or absence of stone material on 
postoperative day 1 CT imaging 
This study is a post-market, prospective, randomized, multicenter, 2-arm, comparative trial. 
Scale and Duration 
A total of 100 subjects will be enrolled and treated at 3 study sites across the USA.  Each subject will be 
followed for approximately 6-12 weeks after the study procedure.  It is anticipated for the entire study 
to last approximately 12 months. 
 
 
*All sites will perform 10 independent PCNL cases, outside of the study period, using the Trilogy 
lithotrite to become accustomed with the device prior to enrolling patients. 

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Protocol Version 7.27.2020 
Treatment Assignment 
The patients will be block randomized 1:1 to either stone removal with the Trilogy or the ShockPulse–SE 
device.  All randomization will occur at the central study site via computer randomization by the 
statistician to limit selection bias.   
Justification for the Study Design 
This study will compare performance of two devices for the treatment of large renal calculi.  The study 
has been designed as a prospective, multi-centric, randomized, comparative study.  The intent of this 
design is to minimize bias and to allow for statistical comparison of the two treatment groups. 
Subject Selection  
Study Population and Eligibility  
Patients who meet all of the inclusion criteria and none of the exclusion criteria will be considered for 
inclusion in theis study. 
Inclusion Criteria 
1. ≥ 18 years of age 
2. Stone burden  ≥ 1.5 cm as measured on preoperative CT scan 
3. Patient is scheduled to undergo a percutaneous nephrolithotomy procedure 
4. Willing and able to provide informed consent 
Exclusion Criteria 
1. Pregnant 
2. Active urinary tract infection 
3. Prior shock wave lithotripsy within 3 months of study procedure 
4. Multiple percutaneous access sites are anticipated 
5. Unable or unwilling to provide informed consent 
Subject Accountability 
Point of Enrollment 
A subject will be considered enrolled in the study if they meet all eligibility criteria and after the subject 
signs and dates the informed consent form (ICF).  No study-related procedures can take placed until the 
ICF is signed.  

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Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study or lost to 
follow-up) shall be accounted for and documented. If a subject withdraws from the clinical investigation, 
the reason(s) shall be reported. If such withdrawal is due to problems related to study device safety or 
performance, the investigator shall ask for the subject’s permission to follow his/her status/condition 
outside of the clinical study.  
 
Reasons for withdrawal include:    
• 
Physician discretion 
• 
Subject choice to withdraw consent 
• 
Lost to follow-up 
• 
If the subject dies due to any cause 
 
While study withdrawal is discouraged, subjects may withdraw from the study at any time, with or 
without reason, and without prejudice to further treatment.   
If any treated study patient is unable to return to the study center after treatment, efforts will be made 
to obtain complete follow-up information from the patient’s primary physician. The reason for a 
patient's failure to return for the necessary follow-up visits or for a patient's discontinuance from the 
study must be determined and recorded in the case report forms (CRF).  
All applicable CRFs up to the point of subject withdrawal must be completed.  Subjects who are “lost to 
follow up” should have documented attempts to contact them. 
Additional data may no longer be collected after the point at which a subject has been withdrawn from 
the study or withdraws his/her consent, for whatever reason.  Data collected up to the point of subject 
withdrawal may be used for study analysis. 
Study Methods 
Data Collection 
The schedule of data collection is illustrated in Table 2.

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Procedure/Assess
ment 
Screening/Base
line 
(Clinic Visit) 
ShockPulse-SE or 
Trilogy Procedure 
(Hospital Visit) 
Follow-up Visits 
6-12 Week Visit3 
(Clinic Visit) 
Unscheduled 
Visit2 
(Clinic Visit) 
Visit Window 
Within 90 Days 
Prior to 
Procedure 
 
 
 
Informed Consent 
Form 
X 
 
 
 
Selection Criteria 
X 
 
 
 
Randomization 
X 
 
 
 
Demographics 
X 
 
 
 
CT Scan& Stone 
Information  
X 
 
 
 
Medical History 
X 
 
 
 
Pre-operative 
Physical Exam 
and Laboratory 
Data 
X 
 
 
 
Lithotripsy 
Procedure 
 
X 
 
 
Stone Free Status 
 
X1 
X1 
 
Post-operative 
Stone and 
Laboratory Data 
 
X 
 
 
Device 
Malfunctions 
 
X 
 
 
Adverse Events 
 
X 
X 
X 
 
1 Stone Free Status must be assessed on POD 1 by CT.  2 Unscheduled Visits may be performed between protocol specified visits as deemed 
appropriate by the investigator.3 End of study will be reached after completion of the 6-12 Week Follow-up visit, subject withdrawal, or lost 
to follow-up, whichever occurs first.

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Informed Consent 
All subjects taking part in this clinical study must undergo the informed consent process. Subjects must 
be allowed adequate time to review the consent, raise questions, and make a voluntary decision to 
participate in the clinical study. Each subject must sign and date the IRB approved informed consent 
form before any clinical study-related procedures are performed. A copy of signed informed consent 
form will be provided to the subject for his/her records. A subject’s participation in the clinical study 
begins with the signing and dating of the informed consent form.  
Screening (Clinic Visit): 
The following data will be captured during the Screening Visit: 
• 
Informed consent process 
• 
Inclusion / exclusion criteria 
• 
Randomization 
o All randomization will occur at the central study site via computer randomization by the 
statistician to limit selection bias 
Baseline (Within 90 Days Prior to Procedure) (Clinic Visit): 
 
The following data will be captured during the Baseline Visit: 
• 
Demographics 
• 
CT scan 
• 
Stone burden 
• 
Stone size (cm) 
o Axial x Coronal 
• 
Targeted stone surface area (mm2) 
o This measurement is determined by outlining the CT image of the stone using a digital 
system such as PACS) 
• 
Previous treatment of targeted stone 
• 
Medical history 
• 
Pre-operative physician exam 
o Height, weight, and BMI 
• 
Pre-operative laboratory data  
o Serum creatinine (mg/dl) 
o Hemoglobin (g/dl) 
o Hematocrit (%) 
o Na (mEq/l) 
o Urine culture 
ShockPulse-SE or Trilogy Procedure (Hospital Visit): 
The following data will be captured during the Lithotripsy Procedure Visit: 
 

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Intraoperative Data: 
o Date of surgery 
o Device accountability 
 
The lot number of the disposable devices used shall be captured. 
o Type of Anesthesia 
 
General 
 
IV Sedation 
 
Regional 
o ASA Level 
 
1:  A normal, healthy patient 
 
2:  A patient with mild systemic disease 
 
3:  A patient with severe systemic disease 
 
4:  A patient with severe systemic disease that is a constant threat to life 
o Number and location of access sites for lithotripsy procedure 
o Total procedure time as measured in minutes from induction of anesthesia to end of 
anesthesia 
 
Please ensure these time points exists in the subject’s source documentation 
o Time to clearance of targeted stone burden as measured in minutes 
 
Start time: When the investigator begins to use the lithotriptor on the targeted 
stone 
 
Stop time:  When the investigator has cleared all fragments and prior to final 
inspection of the kidney with the flexible nephroscope 
 
Please ensure these time points exists in the subject’s source documentation 
o Use of other intracorporeal lithotripsy devices including laser 
o Settings utilized for each lithotripter device 
o Stone Free Status 
 
Assessed by CT scan performed postoperative day 1. 
o Estimated blood loss (EBL) 
o Device malfunctions 
o Adverse events 
2.1.1.Post-operative Data: 
o Length of hospitalization measured in days 
o Need for blood transfusion 
o Assessment of nephrostomy tube 
o Adverse events 
o Stone Free Status  
 
Date of imaging study should be provided.   
o Stone analysis 
o Stone culture results 
o Post-operative laboratory data 
 
Serum creatinine (mg/dl) 
 
Hemoglobin (g/dl) 
 
Hematocrit (%) 

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 
Na (mEq/l) 
 
6-12 Week Follow-up Visit (Clinic Visit): 
The following data will be captured during the 6-12 Week Follow-up Visit: 
• 
Stone Free Status  
o Date of imaging study should be provided.  Either a CT or KUB and/or Ultrasound is 
required prior to or during the 6-12 Week Follow-up Visit. 
• 
Adverse events 
Unscheduled Visit (Clinic Visit): 
Unscheduled visits may be performed between visits required by the protocol as deemed necessary by 
the investigator.  Data for unscheduled visits will be captured on the Adverse Event case report form 
(CRF). 
End of Study 
End of study will be reached after completion of the 6-12 Week Follow-up visit, subject withdrawal, or 
lost to follow-up, whichever occurs first. 
Source Documents 
Source documents are the patient records maintained at the study site. In most cases, the source 
documents will be the physician’s or hospital’s patient chart. In some cases, the source documents may 
be electronic. In both cases, the information captured in the CRF must match the information in the 
chart or electronic source document. 
Statistical Considerations 
Endpoints 
 
Primary Endpoint 
Stone clearance rate. 
Hypothesis 
It is hypothesized that the Trilogy will reduce the stone clearance rate by 25% compared to the 
Shockpulse-SE.   
 
 
Additional Endpoints 
Additional endpoints include the following: 
1. Device malfunctions 

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Protocol Version 7.27.2020 
2. All complications measured by the Clavien Classification of Surgical Complications 
3. Stone free status as defined by the presence or absence of stone material on postoperative 
imaging  
• 
Stone free status must be assessed prior POD #1 by CT scan. 
Analysis Sets 
The Intent-To-Treat (ITT) dataset will consist of all patients who were randomized and is defined by all 
subjects being grouped by their initial randomization, regardless of the actual treatment received. 
The Per Protocol (PP) dataset will consist of all randomized subjects who underwent their assigned 
treatment and full outcome assessment. 
The Safety Analysis (SA) dataset consists of all subjects who received any amount of treatment on 
protocol. 
 
Sample Size  
For simplicity, sample size calculations were performed using a two-sided Student t-test with a power of 
90% and a significance level of alpha = 0.05.  The primary outcome of interest is the clearance rate of the 
targeted stone burden.  Preliminary in vitro data shows a reduction of approximately 50% in the average 
lithotripter clearance time of a 1 cm3 BegoStone for the Trilogy lithotrite compared to the ShockPulse-
SE.  Given the increased variability of use in vivo and across subjects, a more conservative difference was 
considered for sample size estimation.  Assuming a 25% improvement in clearance rate that results in an 
effect size of 0.7, a sample size of 44 subjects in each group is required. To account for the possibility of 
unevaluable data a total of 100 patients, 50 in each group will be enrolled. 
 
Statistical Methods 
All demographic data will be summarized using descriptive statistics (for continuous 
measures; mean, standard deviation, median, min and max and for categorical measures; count 
and percent) and tabulated by treatment group. Distributions of continuous measures will be 
investigated and if found to be significantly non-normal appropriate transformations will be 
sought. Demographics will be compared between groups using Student t-tests and Fisher’s exact 
tests, as appropriate. If any demographics measures are found to be unbalanced between 
groups, they will be considered as possible covariates when analyzing the primary outcome.  
The primary outcome, clearance rate, will be calculated by dividing the stone surface 
area by the clearance time. To compare the clearance rate between groups a mixed effects 
model will be used including treatment group as a fixed effect and site (hospital) as a random 
effect.  Any demographics that were found to be unbalanced between groups may also be 
included in the model as covariates.  

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Device malfunctions will be recorded and summarized by treatment group.  The 
proportion of cases experiencing device malfunctions will be compared between groups using 
Fisher’s Exact test. All subject complications will be recorded and summarized using the Clavien 
Classification of Surgical Complications. The proportions of subjects experiencing complications 
will also be compared between groups using Fisher’s Exact test.  The number (and percent) of 
patients found to be stone free at 6-12 weeks post-op will be summarized and compared 
between groups using Fisher’s Exact test. 
The main analysis of the primary endpoint will be performed on the ITT dataset. Supportive analyses 
may be performed on the PP dataset.  All reporting and analysis of adverse events and complications 
will be done using the SA data set.  
Control of Systematic Error/Bias 
To minimize selection bias there will be a single randomization schedule managed at the lead 
investigative site.  Upon subject enrollment, all participating sites will contact the main site for 
experimental group randomization.  The randomization will be a permuted block randomization that will 
help ensure a reasonable balance of group assignment throughout the study enrollment period. 
Number of Subjects per Investigative Site 
The maximum number of subjects for any single site is 85. 
Data Management 
Data Collection, Processing, and Review 
Subject data will be recorded in a limited access, secure, web-based electronic data capture (EDC) 
system called REDCap.  REDCap is designed to comply with HIPAA regulations. REDCap is not 21 CFR Part 
11 compliant; however, this data will not be submitted to the FDA as it is part of a post-market study 
comparing two commercialized devices for their cleared intended uses. 
The conduct of clinical studies pertaining to the use of electronic records and signatures. Database 
backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case report forms 
(eCRFs) in compliance with local regulations. A written signature on printouts of the eCRFs must also be 
provided if required by local regulation. Changes to data previously submitted to the sponsor require a 
new electronic signature by the Investigator acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data discrepancies. Manual 
and/or automatic queries will be created in the EDC system and will be issued to the site for appropriate 
response. Site staff will be responsible for resolving all queries in the database. 
Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain, at the investigative 
site, all essential study documents and source documentation that support the data collected on the 

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study subjects in compliance with regulatory guidelines.  Documents must be retained for at least 2 
years after the last approval of a marketing application or until at least 2 years have elapsed since the 
formal discontinuation of the clinical investigation of the product.  
 
Data Safety Review 
Individual Investigators will conduct continuous review of data and patient safety. Summaries submitted 
to the lead site should include review of data, the number of patients, significant adverse events as 
described in the risks, and responses observed. A combined summary for all sites will be submitted half 
way through enrollment (50 subjects) and at the completion of enrollment (100 subjects) for review by 
the DSMC. 
Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or scientific 
integrity of the data, an amendment is required. Appropriate approvals (e.g., IRB) of the revised 
protocol must be obtained prior to implementation. 
Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency. An investigator shall notify the sponsor and the 
reviewing IRB of any deviation from the investigational plan to protect the life or physical well-being of a 
subject in an emergency, and those deviations which affect the scientific integrity of the clinical 
investigation. Such notice shall be given as soon as possible, but no later than 5 working days after the 
emergency occurred, or per prevailing local requirements, if sooner than 5 working days. 
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor. Sites may also be required to report 
deviations to the IRB/EC, per local guidelines and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate corrective 
and preventive actions (including IRB notification, site re-training, or site discontinuation/termination) 
will be put into place by the sponsor. 
Device/Equipment Accountability 
The study devices/equipment shall be securely maintained, controlled, and used only in this clinical 
study. 

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Protocol Version 7.27.2020 
Compliance 
Statement of Compliance 
This study will be conducted in accordance with ICH Guidelines, Good Clinical Practices ISO 14155, 
ethical principles that have their origins in the Declaration of Helsinki, and pertinent individual country 
laws and regulations. The study shall not begin until the required approval/favorable opinion from the 
IRB authority has been obtained. Any additional requirements imposed by the IRB shall be followed, if 
appropriate.  
Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study is 
conducted in accordance with the Clinical Study Agreement, the clinical investigation plan, ISO 14155, 
ethical principles that have their origins in the Declaration of Helsinki, any conditions of approval 
imposed by the reviewing IRB, and prevailing local and/or country laws and/or regulations, whichever 
affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• 
Prior to beginning the study, sign the Clinical Study Agreement and comply with the Investigator 
responsibilities as described in such Agreement.   
• 
Prior to beginning the study, sign the Protocol Signature page documenting his/her agreement to 
conduct the study in accordance with the protocol. 
• 
Provide his/her qualifications and experience to assume responsibility for the proper conduct of the 
study and that of key members of the site team through up-to-date curriculum vitae or other 
relevant documentation and disclose potential conflicts of interest, including financial, that may 
interfere with the conduct of the clinical study or interpretation of results. 
• 
Make no changes in or deviate from this protocol, except to protect the life and physical well-being 
of a subject in an emergency; document and explain any deviation from the approved protocol that 
occurred during the course of the clinical investigation. 
• 
Create and maintain source documents throughout the clinical study and ensure their availability 
with direct access during monitoring visits or audits; ensure that all clinical-investigation-related 
records are retained per requirements. 
• 
Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in 
the CRFs and in all required reports. 
• 
Record, report, and assess (seriousness and relationship to the device/procedure) every adverse 
event as applicable per the protocol and observed device deficiency. 
• 
Allow and support regulatory authorities and the IRB/EC when performing auditing activities. 
• 
Ensure that informed consent is obtained in accordance with applicable laws, this protocol and local 
IRB/EC requirements. 
• 
Provide adequate medical care to a subject during and after a subject’s participation in a clinical 
study in the case of adverse events, as described in the ICF. 

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Protocol Version 7.27.2020 
• 
Inform the subject of the nature and possible cause of any adverse events experienced. 
• 
Inform the subject of any new significant findings occurring during the clinical investigation, 
including the need for additional medical care that may be required. 
• 
Provide the subject with well-defined procedures for possible emergency situations related to the 
clinical study, and make the necessary arrangements for emergency treatment, including decoding 
procedures for blinded/masked clinical investigations, as needed. 
• 
Ensure that clinical medical records are clearly marked to indicate that the subject is enrolled in this 
clinical study. 
• 
Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided with some 
means of showing their participation in the clinical investigation, together with identification and 
compliance information for concomitant treatment measures (contact address and telephone 
numbers shall be provided). 
• 
Inform, with the subject’s approval or when required by national regulations, the subject’s personal 
physician about the subject’s participation in the clinical investigation. 
• 
Make all reasonable efforts to ascertain the reason(s) for a subject’s premature withdrawal from 
clinical investigation while fully respecting the subject’s rights. 
• 
Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
• 
Ensure that maintenance and calibration of the equipment relevant for the assessment of the 
clinical investigation is appropriately performed and documented, where applicable. 
Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting the 
informed consent process, the Principal Investigator is responsible for providing appropriate training 
and adequate supervision of those to whom tasks are delegated. The investigator is accountable for 
regulatory violations resulting from failure to adequately supervise the conduct of the clinical study.  
 
Institutional Review Board/Ethics Committee 
The protocol and informed consent document must have the approval of a properly constituted 
committee ("Institutional Review Board" / “Ethics Committee”) responsible for approving clinical trials.  
The signed IRB/EC approval letter must identify the documents approved (i.e., list the Investigator's 
name, the protocol title, and date of approval, and informed consent document). A copy of the approval 
of the protocol (or permission to conduct the study) and Informed Consent Form, must be received by 
the sponsor before recruitment of subjects into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study as required 
by local/country or IRB/EC requirements. Copies of the Investigator’s reports and the IRB/EC 
continuance of approval must be provided to the sponsor.  

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Potential Risks and Benefits 
Anticipated Adverse Device Effects  
The following adverse events (AEs) are considered anticipated during percutaneous nephrolithotomy 
procedures and are reflected in the commercial instructions for use (IFU) for each lithotripsy device: 
o Infection 
o Bleeding 
o Damage to the kidney or surrounding organs 
o Other adverse events associated with anesthesia 
 
Each participating site is responsible for recording AEs and classifying them based on the below Clavien 
Classification system: 
Clavien Classification of Surgical Complications 
All adverse events that occur intra-operatively or within the 30 day postoperative period will be 
assessed using the Clavien Classification of Surgical Complications: 
Grade I:   
Any deviation from the normal post-operative course without the need for 
pharmacological treatment or surgical, endoscopic, and radiological interventions. 
 
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics, diuretics, 
electrolytes, and physiotherapy.  This grade also includes wound infections opened at 
bedside. 
Grade II:   Requiring pharmacological treatment with drugs other than such allowed for Grade I 
complications. Blood transfusions and total parenteral nutrition are also included. 
Grade III:   Requiring surgical, endoscopic or radiological intervention. 
 
Grade IIIa:  Intervention not under general anesthesia 
 
Grade IIIb:  Intervention under general anesthesia 
Grade IV: Life-threatening complication (including CNS complications) requiring IC/ICU 
management. 
 
Grade IVa:  Single organ dysfunction (including dialysis) 
 
Grade IVb:  Multi-organ dysfunction 
Grade V: 
Death of a patient 
Suffix “d”: If the patient suffers from a complication at the time of discharge the suffix “d” (for 
disability) is added to the respective grade of complication.  This label indicates the need 
for a follow-up to fully evaluate the complication. 

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Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC Approval 
Any investigator, or IRB/ EC in this Study may discontinue participation in the study or withdrawal 
approval of the study, respectively. Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
 
Abbreviation 
Definition 
AE 
Adverse Event 
CA 
Competent Authority 
CRF / eCRF 
Case Report Form / Electronic Case Report Form 
CRO 
Clinical Research Organization 
CT 
Computed Tomography 
EBL 
Estimated Blood Loss 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISO 
Internal Organization for Standardization 
ITT 
Intent-to-Treat 
KUB 
Kidney, Ureter, and Bladder 

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NEMA 
National Electrical Manufacturers Association 
OD 
Outer Diameter 
PP 
Per Protocol 
SA 
Safety Analysis 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
USA 
United States of America