Flexiva Pulse Laser Fiber Post-Market Patient Registry
Conditions: Urinary Calculi, Benign Prostatic Hyperplasia
Sponsor: Boston Scientific Corporation

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Flexiva Pulse Laser Fiber Post-Market Patient Registry 
Flexiva Pulse Registry 
U0703 
CLINICAL INVESTIGATION PLAN 
 
 
Sponsored By 
Boston Scientific Corporation 
 
300 Boston Scientific Way 
Marlborough, MA 01752, United States 
 
 
Boston Scientific International SA 
Parc Val Saint-Quentin, Bâtiment H 
2 Rue René Caudron 
78960 Voisins le Bretonneux 
France 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
Winnie Chen 
Clinical Project Manager 
Boston Scientific Corporation 
Urology and Pelvic Health 
100 Boston Scientific Way 
Marlborough, MA 01752 
508-561-6931 
Winnie.Chen@bsci.com  
Coordinating Principal 
Investigator 
Mitchell Humphreys, M.D. 
Chair and Professor, Department of Urology 
Dean, Mayo Clinic School of Continuous Professional 
Development 
Endourology Fellowship Director 
 
Mayo Clinic in Arizona 
5777 E Mayo Blvd  
Phoenix, AZ  85054 
480-342-2951    
humphreys.mitchell@mayo.edu   
 
 
 

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Original Release: July 20, 2021 
Current Version: July 20, 2021 
 
 
 
Revision Version 
Protocol Date 
Template 
number and 
version 
Protocol 
Section 
Modified 
Summary of Changes 
 
Justification for 
Modification 
Revision A 
(initial) 
20July2021 
92120219 
Rev/Ver G 
N/A 
N/A 
Initial Release 
 
 
 

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2. Protocol Synopsis 
Flexiva Pulse Laser Fiber Post-Market Patient Registry 
Flexiva Pulse Registry 
Study 
Objective(s) 
To obtain post-market safety and efficacy data for FlexivaTM Pulse High 
Power Single-Use Laser Fibers during lithotripsy and soft tissue 
procedure of holmium laser enucleation of the prostate (HoLEP).  
Indication(s) for 
Use  
Flexiva Pulse ID and Flexiva Pulse ID TracTip laser fibers are intended 
to be used as a device that transmits Ho:YAG laser energy from cleared 
laser consoles to urological anatomy. Flexiva Pulse ID and Flexiva Pulse 
ID TracTip laser fibers are indicated for urologic applications for which 
the laser systems are cleared, limited to endoscopic procedures 
involving vaporization, ablation, hemostasis, coagulation, excision, 
resection, incision of soft tissue, and lithotripsy of urinary calculi. The 
fiber is designed for use with a standard SMA-905 connector and has 
been cleared for surgical use 
(Commercial) 
Device/System 
applied as 
Standard of 
Care and sizes, 
if applicable 
Flexiva Pulse and Flexiva Pulse ID Laser Fibers  
• Flexiva Pulse High Power Single-Use Fiber   
• Flexiva Pulse TracTip High Power Single-Use Fiber  
• Flexiva Pulse ID High Power Single-Use Fiber and  
• Flexiva Pulse ID TracTip High Power Single-Use Laser Fiber  
Study Design 
Multi-center, open label, prospective study to document on-going post-
market safety and performance of Flexiva Pulse High Power Single-Use 
Laser Fibers. 
 
All subjects meeting the enrollment criteria, signing the consent and 
undergoing the lithotripsy/HoLEP procedure with the study device(s) 
will be followed: up to 2 months (60 days) post-discharge from final 
holmium laser lithotripsy procedure for subjects in the lithotripsy cohort 
or up to 6 months (180 days + 60 days) post discharge from HoLEP 
procedure for subjects in the Benign Prostatic Hyperplasia (BPH) 
cohort. 

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Flexiva Pulse Laser Fiber Post-Market Patient Registry 
Flexiva Pulse Registry 
Planned 
Number of 
Subjects 
Approximately 200 subjects will be enrolled and treated for lithotripsy 
of urinary calculi and BPH indications. 
• Lithotripsy Cohort – desired number of subjects: 100 
• BPH Cohort – desired number of subjects: 100 
Planned 
Number of Sites 
/ Countries 
Subjects will be enrolled at approximately 10 sites, starting in the United 
States. Other geographies that have full regulatory approval may be 
considered.  
Primary Safety 
Endpoint 
The primary safety endpoint is the occurrence of Serious Adverse 
Device Effects (SADE) related to Flexiva Pulse Laser Fibers during 
lithotripsy and HoLEP procedures. 
Primary 
Efficacy 
Endpoints 
The primary efficacy endpoints are: 
• In lithotripsy procedures: Stone clearance assessed by stone 
free rates (SFR) at the 1 month follow-up. 
 
Stone free rates are defined as: Clinically nonsignificant, non-
obstructive residual fragments of ≤ 3 mm, asymptomatic and 
no auxiliary procedures performed between the final Flexiva 
Pulse holmium laser lithotripsy procedure and the 1 month 
follow-up. 
 
• In HoLEP procedures:  Improvement in BPH symptoms from 
baseline as measured by favorable change in International 
Prostate Symptom Score (IPSS) at 3 month follow-up. 
Secondary 
Safety Endpoint 
Procedure related adverse events and/or adverse device effects related to 
Flexiva Pulse Laser Fibers, including but not limited to: 
• Perforation 
o For Lithotripsy procedures: anywhere in urinary tract 
o For HoLEP procedures: in prostate capsule, bladder, 
and/or urethra 
• Hemorrhage resulting in blood loss of ≥ 500mL 
• Burn 

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Flexiva Pulse Laser Fiber Post-Market Patient Registry 
Flexiva Pulse Registry 
Secondary 
Efficacy 
Endpoints 
For Lithotripsy procedures: 
• Ability of the laser fiber to deliver energy (successful 
completion of lithotripsy procedure as indicated) 
• Compatibility of the laser fiber with endoscope (including 
successful passage and maneuverability without fracture)  
 
For HoLEP procedures: 
• Improvement in Quality of Life (QoL) from baseline as 
measured by favorable change in International Prostate 
Symptom Score (IPSS) at 3-month follow-up 
• Improvement in uroflowmetry from baseline as measured by 
change in maximum urinary flow rate (Qmax) at 3-month 
follow-up 
• Hemostasis measured by ability to coagulate during HoLEP 
procedure  
• Ability of the laser fiber to deliver energy (successful 
completion of HoLEP procedure as indicated) 
• Compatibility of the laser fiber with endoscope (including 
successful passage and maneuverability without fracture)  
Additional 
Endpoint 
Fiber tip degradation  
Method of 
Assigning 
Patients to 
Treatment 
This is an open label, non-randomized study 
Follow-up 
Schedule 
For Lithotripsy cohort: 
• Baseline: Pre-procedure imaging study report within 60 days 
prior to procedure 
• Lithotripsy Procedure(s): Laser surgery for stone 
fragmentation/removal 
• All follow-up visits within 2 months (60 days) of discharge from 
final holmium laser lithotripsy procedure per site’s Standard of 
Care (SOC) 
 

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Flexiva Pulse Laser Fiber Post-Market Patient Registry 
Flexiva Pulse Registry 
For BPH cohort: 
• Baseline 
• HoLEP Procedure 
• All follow-up visits within 6 months (180 days + 60 days) of 
discharge from HoLEP procedure per site’s SOC 
Study Duration Enrollment is expected to be completed in approximately 12 months; 
therefore, the total study duration is estimated to be approximately 20 
months. 
Participant 
Duration 
The study duration for each subject in the Lithotripsy cohort is expected 
to be up to 2 months (60 days) post discharge from final holmium laser 
lithotripsy procedure. The study duration for each subject in the BPH 
cohort is expected to be up to 6 months (180 days + 60 days) post 
discharge from HoLEP procedure. 
Inclusion 
Criteria 
Enrollment is limited to the following inclusion criteria: 
For Lithotripsy cohort: 
1. Subject is undergoing treatment for urinary calculi 
2. Subject is willing and able to return for all follow-up visits 
 
For BPH cohort: 
1. Subject is ≥ 40 years of age 
2. Subject with a diagnosis of benign prostatic hyperplasia (BPH) 
with lower urinary tract symptoms 
3. IPSS (International Prostate Symptom Score) ≥ 12 
4. Qmax (Peak Flow Rate) ≤ 15 mL/s 
5. Subject is willing and able to return for all follow-up visits 
Exclusion 
Criteria 
Subjects are not permitted to enroll if they meet any of the following 
exclusion criteria: 
For Lithotripsy cohort: 
1. Subject has uncontrolled bleeding disorders and coagulopathy  
2. Subject has untreated urinary tract infection (UTI) 
3. Subject requires simultaneous HoLEP procedure 
 
For BPH cohort: 

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Flexiva Pulse Laser Fiber Post-Market Patient Registry 
Flexiva Pulse Registry 
1. Subject has a diagnosis of bladder cancer 
2. Subject has a diagnosis of prostate cancer 
3. Subject with prostate-specific antigen (PSA) ˃ 10 ng/mL 
suggestive of prostate cancer is not eligible unless patient has 
concomitant negative prostate biopsy 
4. Subject has acute prostatitis, a prostate abscess, or neurogenic 
bladder  
5. Subject has urethral stricture disorder 
6. Subject has uncontrolled bleeding disorders and coagulopathy 
7. Subject has untreated urinary tract infection (UTI) 
8. Subject requires simultaneous upper urinary calculi lithotripsy 
procedure (not applicable to bladder calculi) 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
There is no formal hypothesis test.  
Statistical Test 
Method 
A two-sided 95% confidence interval will be constructed using exact 
(Clopper-Pearson) method to estimate the SADE rate for each treatment 
cohort. 
Sample Size 
Parameters 
The sample size justification is based on a confidence interval (CI) 
approach. As there is limited published literature on the device safety 
measurement in a clinical study setting, a conservative assumption of 
3% SADE rate within 1 month of the procedure for lithotripsy cohort 
and 5% for BPH cohort within 3 months of the HoLEP procedure was 
assumed. Ninety (90) subjects are needed for each cohort to construct a 
95% two-sided CI with a maximum width of8.4% for lithotripsy cohort 
and 10.2% for HoLEP cohort. Assuming 10% attrition within 1 month 
of the procedure for lithotripsy cohort and within 3 months of the 
HoLEP procedure, it is anticipated that 100 treated subjects will be 
required for each procedure cohort.  
 

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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................4 
3. 
TABLE OF CONTENTS .........................................................................................................9 
3.1. Table of Figures .....................................................................................................13 
3.2. Table of Tables ......................................................................................................13 
4. 
INTRODUCTION.................................................................................................................14 
4.1. Background ............................................................................................................14 
4.2. Study Rationale .....................................................................................................15 
5. 
COMMERCIAL DEVICE DESCRIPTION (PART OF STANDARD OF CARE) ..........................16 
5.1. Commercial Device Under Study ........................................................................16 
5.2. Required Medical Equipment ..............................................................................17 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................17 
7. 
STUDY DESIGN .................................................................................................................20 
7.1. Scale and Duration ................................................................................................20 
7.2. Treatment Assignment ..........................................................................................21 
7.3. Justification for the Study Design ........................................................................22 
8. 
SUBJECT SELECTION ........................................................................................................22 
8.1. Study Population and Eligibility ..........................................................................22 
8.2. Inclusion Criteria ..................................................................................................22 
8.3. Exclusion Criteria .................................................................................................22 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................23 
9.1. Point of Enrollment ...............................................................................................23 
9.2. Withdrawal ............................................................................................................23 
9.2.1. 
Voluntary Withdrawal ..............................................................................24 
9.3. Lost to Follow-Up ..................................................................................................24 
9.4. Subject Status and Classification .........................................................................24 
9.5. End-of-Study Definition........................................................................................24 

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10. STUDY METHODS .............................................................................................................25 
10.1. Data Collection ......................................................................................................25 
10.2. Study Candidate Screening ..................................................................................28 
10.2.1. Strategies for Recruitment and Retention .................................................28 
10.3. Informed Consent..................................................................................................28 
10.4. Screening Assessments/Procedures .....................................................................28 
10.5. Baseline Visit..........................................................................................................28 
10.6. Lithotripsy/HoLEP Procedure Visit ....................................................................29 
10.7. Post-Procedure Discharge ....................................................................................30 
10.8. Post Lithotripsy/HoLEP Procedure Follow-up Visits .......................................31 
10.8.1. All SOC Follow-up Visits within 60 days post discharge from final 
Flexiva Pulse holmium laser Lithotripsy procedure .................................31 
10.8.2. All SOC Follow-up Visits within 6 months (180 days + 60 days) post 
discharge from HoLEP procedure ............................................................31 
10.9. Unscheduled Visit ..................................................................................................31 
10.10. 
Study Completion ...................................................................................32 
10.11. 
Source Documents ..................................................................................32 
10.12. 
Local Laboratory documentation .........................................................32 
11. STATISTICAL CONSIDERATIONS ......................................................................................32 
11.1. Endpoints ...............................................................................................................32 
11.1.1. Primary Safety Endpoint ...........................................................................32 
11.1.1.1. Hypotheses ...............................................................................32 
11.1.1.2. Sample Size ..............................................................................32 
11.1.1.3. Statistical Methods ...................................................................33 
11.1.2. Primary Efficacy Endpoints ......................................................................33 
11.1.2.1. Hypotheses ...............................................................................33 
11.1.2.2. Statistical Methods ...................................................................33 
11.2. General Statistical Methods .................................................................................33 
11.2.1. Analysis Sets .............................................................................................33 
11.2.2. Control of Systematic Error/Bias ..............................................................34 
11.2.3. Number of Subjects per Investigative Site ...............................................34 
11.3. Data Analyses ........................................................................................................34 
11.3.1. Secondary Endpoints ................................................................................34 
11.3.1.1. Secondary Safety Endpoint – Procedure related adverse events 
and/or adverse device effects ...................................................34 
11.3.1.2. Secondary Efficacy Endpoint 1 – Ability of the laser fiber to 
deliver energy ...........................................................................34 

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11.3.1.3. Secondary Efficacy Endpoint 2 – Compatibility of the laser 
fiber with endoscope ................................................................35 
11.3.1.4. Secondary Efficacy Endpoint 3 – Improvement in Quality of 
life (QoL) from baseline ..........................................................35 
11.3.1.5. Secondary Efficacy Endpoint 4 – Improvement in uroflow ....35 
11.3.1.6. Secondary Efficacy Endpoint 5 – Hemostasis during HoLEP 
procedure ..................................................................................35 
11.3.2. Additional Endpoint ..................................................................................35 
11.3.2.1. Additional Endpoint – Fiber tip degradation ...........................36 
11.3.3. Interim Analyses .......................................................................................36 
11.3.4. Subgroup Analyses ...................................................................................36 
11.3.5. Justification of Pooling .............................................................................36 
11.3.6. Multivariable Analyses .............................................................................36 
11.3.7. Changes to Planned Analyses ...................................................................36 
12. DATA MANAGEMENT .......................................................................................................36 
12.1. Data Collection, Processing, and Review ............................................................36 
12.2. Data Retention .......................................................................................................37 
13. DEVIATIONS......................................................................................................................37 
14. COMPLIANCE ....................................................................................................................38 
14.1. Statement of Compliance ......................................................................................38 
14.2. Investigator Responsibilities ................................................................................38 
14.2.1. Delegation of Responsibility ....................................................................40 
14.3. Institutional Review Board/ Ethics Committee ..................................................40 
14.4. Sponsor Responsibilities .......................................................................................41 
14.5. General Data Protection Regulations (GDPR) ...................................................41 
14.5.1. Transparency .............................................................................................42 
14.5.2. Rights to Data Subjects .............................................................................42 
14.6. Insurance ................................................................................................................42 
15. MONITORING ....................................................................................................................43 
16. POTENTIAL RISKS AND BENEFITS ...................................................................................43 
16.1. Instructions for Use ...............................................................................................43 
16.2. Risks associated with Participation in the Clinical Study .................................43 
16.3. Risk Minimization Actions ...................................................................................43 
16.4. Anticipated Benefits ..............................................................................................43 

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17. SAFETY REPORTING .........................................................................................................44 
17.1. Reportable Events by investigational site to BSC ..............................................44 
17.2. Definitions and Classification...............................................................................44 
17.3. Relationship to Study Device(s) (Device Under Study and Comparator Device, 
if applicable) and/or Study Procedure ................................................................47 
17.4. Investigator Reporting Requirements .................................................................48 
17.5. BSC Device Deficiencies .......................................................................................50 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators .......50 
17.7. Subject Death Reporting ......................................................................................50 
18. INFORMED CONSENT ........................................................................................................51 
19. COMMITTEES ...................................................................................................................52 
19.1. Safety Monitoring Process ....................................................................................52 
19.2. Clinical Events Committee ...................................................................................52 
20. SUSPENSION OR TERMINATION........................................................................................53 
20.1 Premature Termination of the Study ..................................................................53 
20.1.1 
Criteria for Premature Termination of the Study ......................................53 
20.2 Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC/REB Approval .......................................................................................53 
20.3 Requirements for Documentation and Subject Follow-up ................................53 
20.4 Criteria for Suspending/Terminating a Study Site ............................................54 
21. STUDY REGISTRATION AND RESULTS .............................................................................54 
21.1. Study Registration .................................................................................................54 
21.2. Clinical Investigation Report ...............................................................................54 
21.3. Publication Policy ..................................................................................................54 
22. BIBLIOGRAPHY .................................................................................................................55 
23. ABBREVIATIONS AND DEFINITIONS .................................................................................56 
23.1. Abbreviations.........................................................................................................56 
23.2. Definitions ..............................................................................................................57 
 
 

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3.1. Table of Figures 
Figure 7.1-1: Flexiva Pulse Laser Fiber Post-Market Registry Study Design ........................ 21 
 
3.2. Table of Tables 
Table 5-1: Device Universal Part Numbers (UPNs) ............................................................... 16 
Table 6-1: Overview of Objectives and Endpoints ................................................................. 17 
Table 8.2-1: Inclusion Criteria ................................................................................................ 22 
Table 8.3-1: Exclusion Criteria ............................................................................................... 23 
Table 10.1-1: Data Collection Schedule - Lithotripsy Cohort ................................................ 26 
Table 10.1-2: Data Collection Schedule - BPH Cohort .......................................................... 27 
Table 17.2-1: Safety Definitions ............................................................................................. 45 
Table 17.3-1: Criteria for Assessing Relationship of Study Device(s) (Device Under Study 
and Comparator Device, if applicable) or Procedure to Adverse Event .............. 47 
Table 17.4-1: Investigator Requirements for Reporting ......................................................... 48 
Table 23.1-1: Abbreviations ................................................................................................... 56 
Table 23.2-1: Definitions ........................................................................................................ 57 
 

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4. Introduction 
4.1. Background 
The Holmium:yttrium-aluminum-garnet laser (Ho:YAG), is standard for endourological 
procedures. The Ho:YAG laser is established as the gold standard for endoscopic lithotripsy, 
used efficiently for any stone composition, and can also be used for other applications 
including soft-tissue ablation,  Holmium laser enucleation of the prostate (HoLEP) for Benign 
prostatic hyperplasia (BPH), tumor resections, and management of stricture disease1.  
Urolithiasis is the formation of one or more stones in the bladder or urinary tract. Kidney stones 
are small, hard deposits that can form in the renal pelvis of the kidney. Nonsurgical 
management and treatment of stone disease involves medical relief of pain, and/or medical 
expulsive therapy (MET). Observation of small ureteral stones (< 6 mm) with periodic 
evaluation is feasible in patients who do not develop complications2. Another conservative 
treatment option is MET, which includes the pharmacological use of alpha (α)-blockers, 
calcium channel blockers, or phosphodiesterase type 5 (PDE5) inhibitors.  
Treatment for urolithiasis has evolved from open surgery procedure to now less invasive 
ureteroscopy. As smaller, more flexible endoscopes became available in the 1990s and were 
used in conjunction with holmium laser fibers that can fit and bend in these flexible 
endoscopes, ureteroscopy became a mainstay of urolithiasis treatment3. Miniaturized tools are 
also being used with holmium laser fibers in retrograde intrarenal surgery to treat moderate-
to-large stones rather than using extracorporeal shock wave lithotripsy (ESWL)4. Holmium 
laser fibers may also be used as intracorporeal lithotripters in the smallest of tracts during 
Percutaneous Nephrolithotomy (PCNL) procedures to dust stones of any composition or size5. 
The use of Holmium laser has led to capability of fragmenting all stone types, leading to higher 
stone-free rates while maintaining a safety profile7. 
Another wide application of holmium:YAG laser in endourology is to ablate prostatic tissue in 
BPH patients. A common manifestation of prostate disease is lower urinary tract symptoms 
(LUTS). LUTS can be categorized as storage symptoms (increased frequency, nocturia, 
urgency) and voiding symptoms (feeling of incomplete emptying, intermittency, straining, and 
weak stream)6. Surgical treatment for these symptoms is required in 25-30% of men 50-80 
years of age who suffer from moderate-to-severe LUTS. If left untreated, complications of 
BPH-related benign prostatic obstruction (BPO) may include renal insufficiency, acute urinary 
retention, urinary tract infection, bladder stones, bladder decomposition, urinary incontinence, 
upper urinary tract deterioration and azotemia, and hematuria6. The main goal in treating 
prostatic diseases such as BPO is to alleviate the LUTS. The first step is conservative 
management. Men who are experiencing nonbothersome LUTS may be assessed and managed 
with watchful waiting rather than undergoing medical or surgical treatment right away. These 
patients may also be advised to undergo behavioral (e.g., bladder training, double voiding) and 
dietary changes (e.g., reduction of fluid intake at specific times, avoidance of caffeine or 
alcohol).  
 

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Pharmacological treatment is a common initial step in managing enlarged prostates and 
reducing LUTS. When drug treatments for symptomatic BPH have failed or proven to be 
intolerable due to side effects, surgical options for LUTS are considered. Surgical options 
ranging from minimally invasive to most invasive include prostatic urethral lift (PUL) with 
UroLift, laser procedures (vaporization or enucleation with holmium, thulium, greenlight, or 
diode laser), TUIP (transurethral incision of prostate), TURP (transurethral resection of 
prostate), Rezūm, and open prostatectomy. 
For treatment of BPH, TURP has been considered the gold standard, but the minimally invasive 
procedure of holmium laser enucleation of the prostate is a viable surgical treatment option 
with comparable improvements in IPSS and Qmax to TURP with better hemostasis and in turn, 
a lower risk of blood transfusion. HoLEP is a recommended option by AUA for patients with 
LUTS attributed to BPH as prostate size-independent option, or those who cannot stop 
anticoagulation/antiplatelet therapy.  
In modern-day urology, surgical treatment options have steered away from open surgery for 
both urolithiasis and BPH. Holmium laser is among minimally invasive technologies available 
as alternatives. 
Flexiva Pulse and Flexiva Pulse ID Laser Fibers are state of the art devices for delivering 
holmium laser energy to manage and treat urological pathologies including lithotripsy and 
ablation and coagulation of tissue in urological applications (e.g., BPH).  
4.2. Study Rationale 
Ureteroscopy became a mainstay of urolithiasis treatment as smaller, more flexible endoscopes 
became available that are used in conjunction with holmium laser fibers that can fit and bend 
in these flexible endoscopes8. The holmium laser fibers come in varying sizes. In general, 
larger core fibers (550-1000 µm sizes) are used in a straight configuration with endoscopes 
used in PCNL procedures; whereas, smaller core fibers (≤ 365 µm)  have the greater flexibility 
required for flexible ureteroscopy (fURS) procedures9.  
Holmium laser enucleation of the prostate (HoLEP) is a minimally invasive surgical procedure 
for the treatment of BPH. During a HoLEP procedure, a holmium laser fiber (usually 550 µm 
size10) is passed through an endoscope and used to deliver holmium laser energy for 
enucleation and removal of enlarged prostate tissue away from the prostatic capsule.  
Selecting the right fiber size, and its impact on fiber flexibility and flow rates helps in 
understanding performance of the fiber during clinical use. However, fiber performance and 
safety data in a clinical setting is limited. The objective of the Flexiva Pulse registry is to collect 
on-going post-market safety and performance data for the Flexiva Pulse and Flexiva Pulse ID 
Laser fibers in routine clinical use.  

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5. Commercial Device Description (part of Standard of Care) 
5.1. Commercial Device Under Study 
Flexiva Pulse and Flexiva Pulse ID Laser Fibers are manufactured in multiple sizes and are 
available with either a flat tip or a ball-tip (242 µm size only). The universal product numbers 
(UPNs) for the various models of the subject devices are listed in Table 5-1. 
Flexiva Pulse and Flexiva Pulse ID Laser Fibers are non-implanted, single-use surgical devices 
that transiently penetrates inside the body to deliver holmium laser energy. Their intended 
purpose and indications include urological application for which the laser system is cleared, 
limited to endoscopic procedures involving vaporization, ablation, coagulation, hemostasis, 
excision, resection, incision of soft tissue, and lithotripsy of urinary calculi. Flexiva Pulse and 
Flexiva Pulse ID Laser Fibers are used to treat urinary stones and/or urological soft tissue 
conditions (e.g., benign prostatic hyperplasia). The intended patient population includes 
patients who are candidates for the procedures listed in the indications for use. Flexiva Pulse 
and Flexiva Pulse ID Fibers are contraindicated in patients for whom endoscopic procedures 
are contraindicated. The intended users of this device are physicians and supporting staff 
(surgical technicians and nurses) with experience in urological laser surgery.  
Table 5-1: Device Universal Part Numbers (UPNs) 
Product Description 
UPN Product 
Number 
Quantity 
Maximum 
Power 
Fiber 
Length 
(m) 
Flexiva™ Pulse High Power Single-
Use Laser Fiber, 242 µm 
M006L8405910  
1 
50W 
3.0 
M006L8405911 
5 
Flexiva™ Pulse High Power Single-
Use Laser Fiber, 365 µm 
M006L8405920 
1 
100W 
2.6 
M006L8405921 
5 
Flexiva™ Pulse High Power Single-
Use Laser Fiber, 550 µm 
M006L8405930 
1 
100W 
2.6 
M006L8405931 
5 
Flexiva™ Pulse High Power Single-
Use Laser Fiber, 910 µm 
M006L8405940 
1 
100W 
2.6 
M006L8405941 
5 
Flexiva™ Pulse TracTip™ High 
Power Single-Use Laser Fiber, 242 
µm 
M006L8405960 
1 
50W 
3.0 
M006L8405961 
5 
Flexiva™ Pulse ID High Power 
Single-Use Laser Fiber, 242 µm 
M006L8406910 
1 
50W 
3.0 
M006L8406911 
5 
Flexiva™ Pulse ID High Power 
Single-Use Laser Fiber, 365 µm 
M006L8406920 
1 
100W 
2.6 
M006L8406921 
5 
Flexiva™ Pulse ID High Power 
Single-Use Laser Fiber, 550 µm 
M006L8406930 
1 
100W 
2.6 
M006L8406931 
5 
Flexiva™ Pulse ID High Power 
Single-Use Laser Fiber, 910 µm 
M006L8406940 
1 
100W 
2.6 
M006L8406941 
5 
Flexiva™ Pulse ID TracTip™ High 
Power Single-Use Laser Fiber, 242 
µm 
M006L8406960 
1 
50W 
3.0 
M006L8406961 
5 
Source: Super Fiber Lumenis System Requirements Specification (Windchill 92114496) 

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A copy of the device labeling and Instructions for Use (IFU) will be provided in local 
language(s) as required per national regulation. An Investigational Brochure has not been 
developed and per ISO 14155 is not required for this post-market observational clinical 
investigation as commercial product information is available and study device(s) are used 
within the approved indication. 
5.2. Required Medical Equipment  
Equipment for lithotripsy and BPH HoLEP procedures per standard of care will be used 
including but not limited to a high power holmium laser console.  
6. Study Objectives and Endpoints 
The objective of this study is to obtain post-market safety and efficacy data for Flexiva Pulse 
High Power Single-Use Fiber Laser Fiber during Lithotripsy and soft tissue procedure of 
Holmium Laser Enucleation of the Prostate (HoLEP).  An overview of study objectives and 
endpoints are provided in Table 6-1. 
 
Table 6-1: Overview of Objectives and Endpoints 
Objectives 
Endpoints 
Justification for 
Endpoints 
Primary 
The primary objective is to 
assess the clinical safety and 
efficacy of Flexiva Pulse Laser 
Fibers. 
 
Primary Safety Endpoint: The 
occurrence of Serious Adverse 
Device Effects (SADE), related 
to Flexiva Pulse Laser Fibers 
during lithotripsy and HoLEP 
procedures. 
Collect safety events 
in real-world clinical 
setting. 
 

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Objectives 
Endpoints 
Justification for 
Endpoints 
Primary Efficacy Endpoints: 
 
• In lithotripsy procedures: 
Stone clearance assessed by 
stone free rates (SFR) at 1 
month follow-up. 
 
Stone free rates defined as: 
Clinically nonsignificant, 
non-obstructive residual 
fragments of ≤ 3 mm, 
asymptomatic and no 
auxiliary procedures 
performed between the final 
Flexiva Pulse holmium laser 
lithotripsy procedure and the 
1 month follow-up. 
Stone free rate is 
standard clinical 
outcome measured 
after a URS with 
holmium laser 
lithotripsy procedure.  
• In HoLEP procedures: 
Improvement in BPH 
symptoms from Baseline as 
measured by favorable 
change in International 
Prostate Symptom Score 
(IPSS) at 3 month follow-up. 
IPSS is standard 
clinical measure for 
HoLEP procedure 
Secondary 
 
Secondary Safety Endpoint: 
Procedure related adverse events 
and/or adverse device effects 
related to Flexiva Pulse Laser 
Fibers, including but not limited 
to: 
• Perforation 
o For Lithotripsy 
procedures: anywhere in 
urinary tract 
o For HoLEP procedures: 
in prostate capsule, 
bladder, and/or urethra 
• Hemorrhage resulting in 
blood loss of ≥ 500mL 
• Burn 
 
Procedure related 
AEs and device 
related ADEs will be 
collected in a routine 
clinical setting. The 
overall performance 
of the fibers will be 
collected during the 
lithotripsy and 
HoLEP procedure.  
The IPSS QOL is the 
standard instrument 
for the measurement 
of Lower Urinary 
Tract Symptoms 
(LUTS) severity in 
men with BPH.  
 

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Objectives 
Endpoints 
Justification for 
Endpoints 
Secondary Efficacy Endpoints: 
 
For Lithotripsy procedures: 
• Ability of the laser fiber to 
deliver energy (successful 
completion of lithotripsy 
procedure as indicated) 
• Compatibility of the laser 
fiber with endoscope 
(including successful passage 
and maneuverability without 
fracture)  
  
For HoLEP procedures: 
• Improvement in Quality of 
life (QoL) from baseline as 
measured by favorable 
change in IPSS at 3 month 
follow-up. 
• Improvement in 
uroflowmetry from baseline 
as measured by change in 
maximum urinary flow rate 
(Qmax) at 3 month follow-up 
• Hemostasis measured by 
ability to coagulate during 
HoLEP procedure  
• Ability of the laser fiber to 
deliver energy (successful 
completion of HoLEP 
procedure as indicated) 
• Compatibility of the laser 
fiber with endoscope 
(including successful passage 
and maneuverability without 
fracture)  

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Objectives 
Endpoints 
Justification for 
Endpoints 
Additional 
 
Additional Endpoint: 
• Fiber tip degradation  
Fiber tip degradation 
will be assessed 
subjectively by the 
physician after use of 
the fiber during 
lithotripsy and/or 
HoLEP procedure. 
 
7. Study Design 
This is a multi-center, open label, prospective study to document the safety and performance 
of Flexiva Pulse High Power Single-Use Laser Fiber.  
7.1. Scale and Duration 
This study will include:  
• Approximately 200 subjects will be enrolled at up to 10 sites starting in the United 
States. Other geographies that have full regulatory approval may be considered. 
• There will be about 100 subjects enrolled in the lithotripsy cohort and 100 subjects 
enrolled in the BPH cohort. 
• The enrollment period will be approximately 12 months.  
• This study is expected to take about 20 months from first subject enrollment until the 
study closeout.  
• Each subject will be involved in the study for up to 2 months (60 days) post-discharge 
from final holmium laser lithotripsy procedure for subjects in the lithotripsy cohort or 
up to 6 months (180 days + 60 days) post discharge from HoLEP procedure for subjects 
in the Benign Prostatic Hyperplasia (BPH) cohort. Sites will be encouraged to enroll a 
minimum of 5 subjects per procedure cohort. A maximum of 25 subjects per procedure 
cohort may be enrolled at a site, unless the site has received prior approval from the 
sponsor to enroll additional subjects. 
 
 
 
 

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Figure 7.1-1: Flexiva Pulse Laser Fiber Post-Market Registry Study Design 
 
 
Eligibility and Informed Consent 
Review Eligibility Criteria
Informed consent form and 
HIPAA Authorization signed by patient
Baseline Assessments
Demographics, Medical History, Medications, Physical 
Exam, Laboratory Blood Analysis and Urinalysis/
Culture, Imaging Study Report, COVID-19 Assessment
Lithotripsy Procedure(s)
AEs, Device Deficiency, COVID-19 Assessment
Screen Failure
No further study 
activities
No
Study Exit
Enroll Subject
Yes – Lithotripsy Cohort
Post Procedure Discharge(s)
Medications, AEs, Device Deficiency, 
COVID-19 Assessment
Yes – BPH Cohort
Baseline Assessments
Demographics, Medical History, Medications, Physical 
Exam, Laboratory Blood Analysis and Urinalysis/
Culture, Prostate Volume, PVR, IPSS, Qmax, 
COVID-19 Assessment
HoLEP Procedure 
AEs, Device Deficiency, COVID-19 Assessment
Post Procedure Discharge
Medications, AEs, Device Deficiency, PVR, 
COVID-19 Assessment
Yes
All SOC Follow-up Visits
within 6 Months of Discharge
AEs, IPSS, Qmax, PVR, COVID-19 Assessment
All SOC Follow-up Visits 
within 60 days of Discharge
AEs, Imaging Study Report, COVID-19 Assessment
 
 
7.2. Treatment Assignment 
This is a post-market registry study. Any subject who is indicated for lithotripsy or BPH 
undergoing HoLEP and is willing to provide a written informed consent will be approached 
and considered for enrollment in the study. The subject is considered enrolled in the study once 
the subject has signed the informed consent form and the lithotripsy/HoLEP procedure is 
attempted. Each subject will be assigned a unique subject identifier in the Electronic Data 
Capture (EDC) system.  

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7.3. Justification for the Study Design 
Flexiva Pulse and Flexiva Pulse ID Laser Fibers are commercially available devices that 
transiently penetrate inside the body to deliver holmium laser energy. With a cohort study 
design, enrolling subjects undergoing lithotripsy or HoLEP as standard of care procedure will 
provide real-world safety and performance data. 
8. Subject Selection  
8.1. Study Population and Eligibility  
Approximately 200 subjects will be enrolled and treated for lithotripsy of urinary calculi and 
BPH indications. There will be about 100 subjects enrolled in the lithotripsy cohort and 100 
subjects enrolled in the BPH cohort. 
Subjects will generally be recruited from physician’s practice. Subjects who meet all of the 
inclusion criteria (see Table 8.2-1) and none of the exclusion criteria (see Section 8.3) may be 
given consideration for inclusion in this clinical investigation. 
8.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 8.3) is 
met.  
 
Table 8.2-1: Inclusion Criteria 
Inclusion 
Criteria 
For Lithotripsy cohort: 
1. Subject is undergoing treatment for urinary calculi 
2. Subject is willing and able to return for all follow-up visits 
 
For BPH cohort: 
1. Subject is ≥ 40 years of age 
2. Subject with a diagnosis of benign prostatic hyperplasia with lower 
urinary tract symptoms 
3. IPSS (International Prostate Symptom) Score ≥ 12 
4. Qmax (Peak Flow Rate) ≤ 15 mL/s 
5. Subject is willing and able to return for all follow-up visits 
 
8.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 8.3-1) cannot be included in this 
study or will be excluded from this clinical study. 

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Table 8.3-1: Exclusion Criteria 
Exclusion 
Criteria 
For Lithotripsy cohort: 
1. Subject has uncontrolled bleeding disorders and coagulopathy  
2. Subject has untreated urinary tract infection (UTI) 
3. Subject requires simultaneous HoLEP procedure  
 
For BPH cohort: 
1. Subject has a diagnosis of bladder cancer 
2. Subject has a diagnosis of prostate cancer 
3. Subject with prostate-specific antigen (PSA) ˃ 10 ng/mL suggestive 
of prostate cancer is not eligible unless patient has concomitant 
negative prostate biopsy 
4. Subject has acute prostatitis, a prostate abscess, or neurogenic 
bladder  
5. Subject has urethral stricture disorder 
6. Subject has uncontrolled bleeding disorders and coagulopathy  
7. Subject has untreated urinary tract infection 
8. Subject with simultaneous upper urinary calculi lithotripsy and 
HoLEP procedure (not applicable to bladder calculi) 
 
9. Subject Accountability 
9.1. Point of Enrollment 
A subject will be considered enrolled in the study after the subject signs and dates the informed 
consent form (ICF) and the lithotripsy/HoLEP procedure is attempted. No study specific (non-
standard of care) procedure(s) or assessment(s) can take place until the informed consent is 
signed.    
9.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
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 device safety 
or performance, the investigator shall ask for the subject’s permission to follow the subject’s 
status/condition outside of the clinical study.  
 
Reasons for withdrawal include but are not limited to physician discretion and subject choice 
to withdraw consent. While study withdrawal is discouraged, subjects may withdraw from the 
study at any time, with or without reason, and without prejudice to further treatment. All 
applicable electronic Case Report Forms (eCRFs) up to the point of subject withdrawal and an 
End of Study eCRF must be completed. Additional data may no longer be collected after the 
point at which a subject has been withdrawn from the study or the subject withdraws consent. 

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Data collected up to the point of subject withdrawal may be used for study analysis, unless 
local regulations apply. 
9.2.1. Voluntary Withdrawal 
Subjects may withdraw from the study at any time. At the time of withdrawal, the Investigator 
shall document the reason for the withdrawal. For subjects who withdraw from the study and 
decide to revoke their authorization to use and disclose their medical information, the 
information that has already been collected in the study record may continue to be used; 
however, no new information will be obtained or added. 
9.2.2.  Involuntary Withdrawal 
Subjects may be involuntarily withdrawn from the study if the Investigator determines it is in 
the subject’s best interest. If the subject is withdrawn at the investigator’s discretion, the reason 
for withdrawal must be documented in the subject’s medical records.  
9.3. Lost to Follow-Up 
If a subject fails to return to the clinic and/or is unable to be reached for a follow-up visit the 
site will attempt to contact the subject and reschedule the missed visit and counsel the subject 
on the importance of maintaining the assigned visit schedule and ascertain if the subject wishes 
to and/or should continue in the study.  
Before the subject may be considered lost to follow-up, the investigator must make the 
following attempts to contact the subject: 
• Three documented telephone attempts 
• One certified letter 
If the subject can be reached and no longer wishes to participate in the study, the Investigator 
shall document the reason for the withdrawal and complete the End of Study eCRF. 
If the subject is not able to be reached after the required attempts to contact the subject have 
been made and the subject has missed two consecutive follow-up visits, the subject may be 
considered lost to follow-up. The Investigator should document in the subject’s medical record 
the attempts to contact the subject and the reason for withdrawal. 
9.4. Subject Status and Classification 
A subject will be considered enrolled after a signed informed consent form is obtained and the 
lithotripsy/HoLEP procedure is attempted. A subject’s participation ends when he or she has 
completed all phases of the study including the last visit as shown in the Data Collection 
Schedule (see Table 10.1-1 and Table 10.1-2). 
9.5. End-of-Study Definition  
The study is considered completed when participants are no longer being examined or the last 
participant’s last study visit has occurred, and study closeout activities are completed.  

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A subject is considered to have completed the study after the subject has completed all phases 
of the study including the last visit shown in the Data Collection Schedule (see Table 10.1-1 
and Table 10.1-2). 
The end of the study is defined as completion of the final Clinical Study Report. 
10. Study Methods 
10.1. Data Collection 
The data collection schedule is shown in Table 10.1-1 and Table 10.1-2. Assessments will be 
completed based on standard of care practices at the site. For Lithotripsy Cohort, data from all 
SOC follow-up visits within 60 days of discharge from final Flexiva Pulse holmium laser 
Lithotripsy procedure will be collected. For BPH Cohort, data from all SOC follow-up visits 
within 6 months (180 days + 60 days) of discharge from HoLEP procedure will be collected. 
All study data will be recorded on source documentation and captured within electronic Case 
Report Forms (eCRFs) for the purposes of this study. Study data will be monitored by Boston 
Scientific or representatives and as applicable on a regular basis as outlined in the study 
Monitoring Plan. 
 

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Table 10.1-1: Data Collection Schedule - Lithotripsy Cohort 
 
Procedure/ Assessment 
Screening 
Baseline3 
Lithotripsy 
Procedure2 
Post Procedure 
Discharge2 
Post final Flexiva Pulse 
holmium laser 
Lithotripsy Procedure 
Follow-up (FU) Visits 
Unscheduled 
Visit  
All SOC FU visits within 
2 months (60 days) of 
discharge 
Eligibility criteria 
X 
 
 
 
 
 
Informed consent process, including informed consent 
signature date 
X 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Medical history  
 
X 
 
 
 
 
Physical examination, including weight and height 
 
X 
 
 
 
 
Imaging Study Report 
 
X 
 
 
X4 
 
Medications 
 
X 
 
X 
 
 
Laboratory Blood Analysis for Lithotripsy Cohort: CBC, 
coagulation testing (PT, PTT, INR), serum creatinine, 
uric acid, CRP, BMP 
 
X1 
 
 
 
 
Laboratory Urinalysis/Culture: Pregnancy Test and UTI 
 
X 
 
 
 
 
Adverse Events assessment 
 
 
X 
X 
X 
X 
Device Deficiency assessment 
 
 
X 
X 
 
 
COVID-19 Assessment 
 
X1 
X1 
X1 
X1 
X1 
X = required 
1 = If available 
2 = If additional Flexiva Fiber holmium laser lithotripsy procedure is performed, complete additional procedure and discharge CRF   
3 = Pregnancy test and urinalysis/culture must be completed within 30 days of procedure, and all other baseline data may be within 60 days 
4 = At least one imaging study report required within 60 days of discharge for stone free rate assessment  
 
 

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Table 10.1-2: Data Collection Schedule - BPH Cohort 
 
Procedure/ Assessment 
Screening 
Baseline3 
HoLEP 
Procedure 
Post Procedure 
Discharge 
Post HoLEP Procedure 
Follow-up (FU) Visits 
Unscheduled 
Visit 
All SOC FU visits within 
6 months (180 days + 60 
days) of discharge  
Eligibility criteria 
X 
 
 
 
 
 
Informed consent process, including informed consent 
signature date 
X 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Medical history  
 
X 
 
 
 
 
Physical examination, including weight and height 
 
X 
 
 
 
 
Prostate Volume 
 
X 
 
 
 
 
Medications 
 
X 
 
X 
 
 
Laboratory Blood Analysis for BPH Cohort:  
CBC, coagulation testing (PT, PTT, INR), PSA 
 
X1 
 
 
 
 
Laboratory Urinalysis/Culture: UTI 
 
X 
 
 
 
 
Post Void Residual 
 
X1,2 
 
X1,2 
X1,2 
 
IPSS 
 
X2 
 
 
X2 
 
Maximum urinary flow rate (Qmax) 
 
X1,2 
 
 
X1,2 
 
Adverse Events assessment 
 
 
X 
X 
X 
X 
Device Deficiency assessment 
 
 
X 
X 
 
 
COVID-19 Assessment 
 
X1 
X1 
X1 
X1 
X1 
X = required 
1 = If available 
2 = If subject does not have a catheter 
3 = Urinalysis/culture must be completed within 30 days of procedure, and all other baseline data may be within 60 days 
 

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10.2. Study Candidate Screening 
All interested subjects will undergo screening during which their eligibility for the study will 
be determined. Sites are expected to follow standard of care testing to diagnose and screen 
subjects for inclusion in the study.  
Subjects who do not meet the inclusion/exclusion criteria are considered screen failures.   
If the subject has completed the informed consent process and met all inclusion and none of the 
exclusion criteria, the subject will progress to the Lithotripsy/HoLEP procedure and follow-up 
phase of the study. 
10.2.1. Strategies for Recruitment and Retention 
Subjects will be recruited from clinician practice who are receiving device as standard of care. 
10.3. Informed Consent 
Written informed consent must be obtained from all potential study candidates before any 
study specific, non-standard of care screening tests or procedures are performed. Only current 
Institutional Review Board (IRB), Ethics Committee (EC) or Research Ethics Board (REB) 
approved study specific ICF must be used. Study personnel should explain that even if a subject 
agrees to participate in the study and signs an ICF, certain screening procedures might 
demonstrate that the subject is not eligible to continue participation. Written informed consent 
must be recorded appropriately by means of the subject’s dated signature.   
10.4. Screening Assessments/Procedures 
The Screening and Baseline visits may occur on the same day or on different days. The 
following must be completed prior to collecting baseline data described in section 10.5:  
• Review of Eligibility Criteria 
• Informed Consent Process, including informed consent signature  
10.5. Baseline Visit  
The Baseline Visit and assessments will occur prior to the subject having Lithotripsy/HoLEP 
procedure. Pregnancy test and urinalysis/culture must be completed within 30 days of 
procedure, and all other baseline data may be completed within 60 days of procedure.  
The baseline assessments below can be completed on the same day as Screening. 
Baseline Assessments for both cohorts 
• Demographics: Age, Gender, Race and Ethnicityy 

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• Medical History: Only current medical conditions in the past 12 months prior to Baseline 
assessment and lifetime history of stones and/or BPH (including all surgical and medical 
treatments).  
• Physical Examination 
• Medications: only active medications at Baseline and lifetime history of medications for 
treatment of stones and/or BPH. 
• Urinalysis/culture 
• Urinary Tract Infection status 
• COVID-19 assessment: prior diagnosis, test result, vaccination status (if available) 
 
Baseline Assessments for Lithotripsy cohort only 
• Imaging Study Report: Computed Tomography (CT) or x-ray or ultrasound of kidneys, 
ureters, and bladder (KUB) – Lithotripsy cohort only 
• Laboratory Blood Tests (if available): Complete Blood Count (CBC), coagulation testing 
(Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio), serum 
creatinine, uric acid, C-Reactive Protein, Basic Metabolic Panel 
• Pregnancy test for women of child-bearing potential 
 
Baseline Assessments for BPH cohort only 
• Prostate Volume – BPH cohort only 
• Laboratory Blood Tests (if available): Complete Blood Count, coagulation testing 
(Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio), 
Prostate Specific Antigen 
• International Prostate Symptom Score (IPSS) – except if patient is catheterized and IPSS 
cannot be done. 
• Maximum urinary flow rate (Qmax) – except if patient is catheterized and uroflow test 
cannot be done (if available) 
• Post Void Residual (PVR), except if patient is catheterized and PVR cannot be done (if 
available) 
10.6. Lithotripsy/HoLEP Procedure Visit  
Lithotripsy/HoLEP procedure is defined as the start time of sedation and/or anesthesia and 
includes the entirety of the holmium laser Lithotripsy or HoLEP procedure. The procedure will 
be performed by a trained physician and per the Flexiva Pulse Laser Fiber IFU.  
It is recommended that surgeons perform a second evaluation at the time of the lithotripsy 
procedure to ensure all stones have been removed.  

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If multi-staged lithotripsy procedures are performed using the Flexiva Pulse Laser Fibers, then 
data will also be collected on the additional procedures. If the additional lithotripsy 
procedure performed does not use the Flexiva Pulse Laser Fibers, then subject should be 
exited from the study at the time of the additional procedure.  
If subject is undergoing HoLEP and simultaneous holmium laser lithotripsy using Flexiva 
Pulse Laser Fibers to remove bladder calculi, data will also be collected on the lithotripsy 
procedure. 
Baseline visit information may be collected on same day, prior to the Lithotripsy/HoLEP 
procedure. 
After the Lithotripsy/HoLEP procedure, the following data will be collected: 
• Procedure information and evaluation of applicable BSC devices used. It is recommended 
that User Feedback Evaluations are completed within 1 week of procedure.   
• Fiber Information – type, size, number of fibers used, model of scope, number of passes 
per fiber, fiber fracture, fiber deflection, if fiber was stripped/cleaved 
• Fiber Performance – fiber tip degradation 
• Assessment of adverse events and device deficiencies  
• COVID-19 assessment: prior diagnosis, test result, vaccination status (if available) 
 
10.7. Post-Procedure Discharge 
At the time of post-procedure discharge, the following information will be collected: 
Lithotripsy Cohort  
• Medications 
• Assessment of adverse events and device deficiencies  
• COVID-19 assessment: prior diagnosis, test result, vaccination status (if available) 
 
Note: If multi-staged procedures are performed using the Flexiva Pulse fibers, then discharge 
data will also be collected on the additional procedures. 
 
BPH Cohort 
• Medications 
• Post Void Residual (PVR) if subject is discharged to home without a catheter (if available) 
• Assessment of adverse events and device deficiencies  
• COVID-19 assessment: prior diagnosis, test result, vaccination status (if available) 
 

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10.8. Post Lithotripsy/HoLEP Procedure Follow-up Visits 
10.8.1. All SOC Follow-up Visits within 60 days post discharge from final Flexiva Pulse 
holmium laser Lithotripsy procedure 
For any follow-up visit(s) that occurs within 60 days post discharge from final Flexiva Pulse 
holmium laser lithotripsy procedure per site’s standard of care, the following assessments will 
be performed and data points collected if available: 
• Imaging Study Report: Computed Tomography (CT) or x-ray or ultrasound of kidneys, 
ureters, and bladder (KUB). At least one imaging study report is required within 60 
days of discharge for stone free rate assessment. 
• Assessment of adverse events 
• COVID-19 assessment: prior diagnosis, test result, vaccination status  
• Study Exit at last follow-up visit within 60 days post discharge 
10.8.2. All SOC Follow-up Visits within 6 months (180 days + 60 days) post discharge 
from HoLEP procedure  
For any follow-up visit(s) that occur within 6 months (180 days + 60 days) post discharge from 
HoLEP procedure per site’s standard of care, the following assessments will be performed and 
data points collected: 
• Post Void Residual (if available) 
• International Prostate Symptom Score (IPSS) 
• Maximum urinary flow rate (if available)  
• Assessment of adverse events 
• COVID-19 assessment: prior diagnosis, test result, vaccination status (if available)  
• Study Exit at last follow-up visit within 6 months (180 days + 60 days) post discharge 
10.9. Unscheduled Visit 
Subjects may have additional visits (other than the study visits specified above), that are 
unplanned visits and are considered as unscheduled visits. Some examples of these visits may 
include a visit for a change in symptoms or to check on a medical event that could not be 
resolved during one of the scheduled study visits. 
 
If an unscheduled visit occurs, the following information will be collected: 
• Assessment of adverse events 
• COVID-19 assessment: prior diagnosis, test result, vaccination status (if available) 

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10.10. 
Study Completion 
Each subject in the Lithotripsy cohort will be followed up to 60 days post discharge from final 
Flexiva Pulse holmium laser Lithotripsy procedure per site’s SOC. Each subject in the BPH 
cohort will be followed up to 6 months (180 days + 60 days) post discharge from HoLEP 
procedure per site’s SOC. All subjects completing the last follow-up visit per site’s SOC and 
their respective cohorts, will be considered to have completed the study. Subjects with any 
ongoing Adverse Events at the end of the study should be followed per institutions’ standard 
of care. 
If subject in the Lithotripsy cohort is undergoing a multi-staged lithotripsy procedure that does 
not use the Flexiva Pulse Laser Fibers, then subject should be exited from the study at the time 
of the additional procedure.  
10.11. 
Source Documents 
It is preferable that original source documents are maintained, when available. In lieu of 
original source documents, certified copies are required to be maintained.  A certified copy is 
a copy (irrespective of the type of media used) of the original record that has been verified (i.e., 
by a dated signature or by generation through a validated process) to have the same 
information, including data that describe the context, content, and structure, as the original.  
10.12. Local Laboratory documentation 
The laboratory (blood and urine) analysis, collected in the study will be completed at the 
local centers per standard of care. Appropriate laboratory certifications and documentation 
records are required to be maintained at the site. 
11. Statistical Considerations 
11.1.  Endpoints 
11.1.1. Primary Safety Endpoint 
The primary safety endpoint is the occurrence of any Serious Adverse Device Effects (SADE) 
(including burn, perforation, and hemorrhage) during Lithotripsy and BPH procedures. 
11.1.1.1. Hypotheses 
There is no formal hypothesis test. The study is designed to evaluate primary safety endpoints 
with desired precision. 
11.1.1.2. Sample Size  
The sample size justification is based on a confidence interval (CI) approach. As there is 
limited published literature on the device safety measurement in a clinical study setting, a 
conservative assumption of 3% SADE rate within 1 month of the procedure for lithotripsy 
cohort and 5% for BPH cohort within 3 months of the HoLEP procedure was assumed. Ninety 

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(90) subjects are needed for each cohort to construct a 95% two-sided CI with a maximum 
width of 8.4% for lithotripsy cohort and 10.2% for HoLEP cohort. Assuming 10% attrition 
within 1 month of the procedure for lithotripsy cohort and within 3 months of the HoLEP 
procedure, it is anticipated that 100 treated subjects will be required for each procedure cohort. 
11.1.1.3. Statistical Methods 
A two-sided 95% confidence interval will be constructed using exact (Clopper-Pearson) 
method to estimate the SADE rate at 30 days post procedure for lithotripsy cohort and the 
SADE rate at 3-month post procedure for BPH cohort. 
11.1.2. Primary Efficacy Endpoints 
Lithotripsy procedure cohort: Stone clearance assessed by stone free rates (SFR) at 1 month 
follow-up. SFR is defined as clinically nonsignificant, non-obstructive residual fragments of ≤ 
3 mm, asymptomatic and no auxiliary procedures performed between the final Flexiva Pulse 
holmium laser lithotripsy procedure and the 1 month follow-up.  
BPH procedure cohort: Improvement in BPH symptoms from Baseline as measured by 
favorable change in International Prostate Symptom Score (IPSS) at 3-month follow-up. 
11.1.2.1. Hypotheses 
There is no pre-specified hypothesis. All the endpoints are descriptive in nature. 
11.1.2.2. Statistical Methods 
Lithotripsy procedure cohort: The proportion of subjects who achieved stone clearance at 1 
month follow-up post lithotripsy procedure will be calculated.  
BPH procedure cohort: The change of IPSS total score at 3-month and 6-month post BPH 
procedure from baseline will be summarized using descriptive statistics. The same analysis 
will be performed for subjects with and without catheter at baseline if applicable. 
11.2. General Statistical Methods 
11.2.1. Analysis Sets 
The Intent-to-Treat (ITT) subject population includes all subjects who provide written 
informed consent to be enrolled into the study, and have the Lithotripsy or BPH procedure 
attempted. 
The As Treated (AT) subject population includes all the ITT subjects who had the Lithotripsy 
or BPH procedure completed. 
The Per Protocol (PP) subject population includes all the AT subjects who also meet all 
eligibility criteria and have no major protocol deviations. 
The primary analysis of all the endpoints will be performed for the ITT population. Efficacy 
endpoints will be evaluated for the PP population as a sensitivity analysis and safety endpoints 
will be evaluated for the AS population as a sensitivity analysis.   

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11.2.2. Control of Systematic Error/Bias 
Registry is open to subjects planning to undergo a procedure with the Flexiva Pulse and Flexiva 
Pulse ID Laser Fibers for any indication per the IFU and at multiple centers. All subjects will 
be treated according to the directions in the Operating Manual and IFU/DFU. The primary 
safety endpoint analysis which is based on the exact Clopper-Pearson confidence interval is 
specified to be conservative in nature. 
11.2.3. Number of Subjects per Investigative Site 
The study will be conducted at up to 10 sites. Sites will be encouraged to enroll a minimum of 
5 subjects per procedure cohort. A maximum of 25 subjects per procedure cohort may be 
enrolled at a site, unless the site has received prior approval from the sponsor to enroll 
additional subjects.  
11.3. Data Analyses 
The analyses will include the available cases only unless specified otherwise. Presentation of 
summary statistics for continuous variables will include N, mean, median, standard deviation, 
minimum, and maximum values. For categorical variables, the number and percentage under 
each category will be presented  
11.3.1. Secondary Endpoints  
11.3.1.1. Secondary Safety Endpoint – Procedure related adverse events and/or adverse 
device effects 
This endpoint applies to both procedure cohorts. Procedure related adverse events and/or 
adverse device effects related to Flexiva Pulse Laser Fibers including but not limited to: 
• Perforation 
o For HoLEP procedures: in prostate capsule, bladder, and/or urethra 
o For Lithotripsy procedures: anywhere in urinary tract 
• Hemorrhage resulting in blood loss of ≥ 500mL 
• Burn 
11.3.1.1.1 Statistical Methods 
For each procedure cohort, summary statistics will be calculated for overall device and/or 
procedure related AEs, and for the device and/or procedure related perforation, hemorrhage 
and burn effects, respectively. The summary statistics includes but not limited to event count, 
event rate  by seriousness procedure relatedness, and device relatedness. 
11.3.1.2. Secondary Efficacy Endpoint 1 – Ability of the laser fiber to deliver energy 
This endpoint applies to both procedure cohorts. This endpoint is measured by whether or not 
the index procedure was successfully completed as indicated. 

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11.3.1.2.1 Statistical Methods 
For each procedure cohort, the proportion of subjects who had successful completion of the 
index procedure will be estimated. 
11.3.1.3. Secondary Efficacy Endpoint 2 – Compatibility of the laser fiber with endoscope 
This endpoint applies to both procedure cohorts. It is measured by whether of not the laser 
fiber is compatible with the endoscope used in the index procedure, including successful 
passage and maneuverability without fracture.  
11.3.1.3.1 Statistical Methods 
The proportion of fibers which are compatible with the endoscope among all the fiber used in 
the index procedure will be estimated.  
11.3.1.4. Secondary Efficacy Endpoint 3 – Improvement in Quality of life (QoL) from 
baseline 
This endpoint applies to HoLEP procedure cohort only. The QoL improvement is measured by 
favorable change in IPSS total score and IPSS QoL score at 3-month follow up from baseline. 
11.3.1.4.1 Statistical Methods 
The change of IPSS total and QoL scores at 3-month post HoLEP procedure from baseline will 
be summarized using descriptive statistics. 
11.3.1.5. Secondary Efficacy Endpoint 4 – Improvement in uroflow 
This endpoint applies to HoLEP procedure cohort only. Improvement in uroflow is measured 
by the change of maximum urinary flow rate (Qmax) at 3-month follow up from baseline. 
11.3.1.5.1 Statistical Methods 
The change of Qmax at 3-month post HoLEP procedure from baseline will be summarized 
using descriptive statistics. 
11.3.1.6. Secondary Efficacy Endpoint 5 – Hemostasis during HoLEP procedure 
This endpoint applies to HoLEP procedure cohort only. Hemostasis is measured by ability to 
coagulate during HoLEP procedure. 
11.3.1.6.1 Statistical Methods 
The proportion of subjects in whom the hemostasis has been achieved as intended during the 
index HoLEP procedurewill be estimated. 
11.3.2. Additional Endpoint  
The additional endpoint apply to both lithotripsy procedure and HoLEP procedure cohorts. 

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11.3.2.1. Additional Endpoint – Fiber tip degradation  
Fiber tip degradation is measured with a three-level scale of ‘Outperformed’, ‘Equivalent’ and 
‘Underperformed’ compared to physician’s current fiber. 
11.3.2.1.1 Statistical Methods 
Proportion of fibers that are used in the Lithotripsy/HoLEP procedure with tip degradation will 
be calculated by each response scale for each procedure groups. 
11.3.3. Interim Analyses  
No formal interim analyses are planned for the purpose of stopping the study early for declaring 
effectiveness or for futility.  
11.3.4. Subgroup Analyses 
Primary safety and efficacy endpoints will be evaluated for subjects in the subgroups listed 
below if applicable: 
* With and without staged procedure in the Lithotripsy procedure cohort. 
* Unilateral and bilateral procedures in the Lithotripsy procedure cohort. 
* With and without previous BPH surgery in the HoLEP procedure cohort. 
11.3.5. Justification of Pooling 
Fisher’s exact test will be applied to evaluate the homogeneity of the primary safety endpoint 
across study sites for each procedure cohorts respectively. Sites with less than 5 ITT subjects 
will be pooled together. 
11.3.6. Multivariable Analyses 
There are no planned multivariable analyses.  
11.3.7. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan approved prior to performing the analyses. 
Changes from the planned statistical methods after performing the analyses will be 
documented in the clinical study report along with a reason for the deviation. 
12. Data Management 
12.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) system.  

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The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides their 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 Medidata EDC system and will be 
issued to the site for appropriate response. Site staff will be responsible for resolving all queries 
in the database. 
All access to the clinical database will be changed to “Read only” after all data is either “Hard 
Locked” or “Entry Locked”. Once acceptance of the final report or finalization of publications 
(as applicable) is received, final database storage and archiving activities can begin. Once all 
closeout activities are completed, a request to IT is submitted to have the “Database Locked” 
or Decommissioned and all database access revoked. 
12.2. Data Retention 
The Principal Investigator or designee or Investigational site will maintain all essential study 
documents and source documentation that support the data collected on the study subjects in 
compliance with applicable regulatory requirements.   
The Principal Investigator or designee will take measures to prevent accidental or premature 
destruction of these documents. If for any reason the Principal Investigator or designee 
withdraws responsibility for maintaining these essential documents, custody must be 
transferred to an individual who will assume responsibility and BSC must receive written 
notification of this custodial change. Sites are required to inform BSC in writing where paper 
or electronic files are maintained in case files are stored off site and are not readily available. 
13. 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/EC/REB, and the regulatory authority if applicable 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.  

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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 by completing the Protocol 
Deviation eCRF in Rave EDC. Sites may also be required to report deviations to the 
IRB/EC/REB, and the regulatory authority, per local guidelines and national/government 
regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/EC notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
The sponsor will not approve protocol waivers.  
14. Compliance 
14.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site can 
be “Authorized to Enroll,” the investigational site must enter into a Clinical Study Agreement 
with the sponsor that details the financing of the study as well as the rights and obligations of 
the investigational site and the investigator. This study will be conducted in accordance with 
applicable FDA regulations (21 CFR 50, 54, 56), ISO 14155: Clinical Investigation of Medical 
Devices for Human Subjects, ICH Good Clinical Practice, ethical principles that have their 
origins in the Declaration of Helsinki, and applicable individual country laws and regulations.  
Applicability of the above principles have been reviewed for this post-market observational 
clinical investigation and justifications for ISO 14155 exemptions are noted in the appropriate 
sections. 
The study shall not begin until the required approval/favorable opinion from the IRB/EC/REB 
and/or regulatory authority has been obtained, if appropriate. Also, the study shall not begin 
prior to issuance of the site Authorization to Enroll, as provided by the sponsor. Any additional 
requirements imposed by the IRB/EC/REB or regulatory authority shall be followed, if 
appropriate.  
14.2. 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, 
the spirit of ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, 
any conditions of approval imposed by the reviewing IRB/EC/REB, 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.   
• Provide personal 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 

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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. 
• Report to sponsor, per the protocol requirements, all reportable events. 
• Report to the IRB/EC/REB and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE and potential/USADE or UADE, if required by applicable 
laws or regulations or this protocol or by the IRB/EC/REB, and supply BSC with any 
additional requested information related to the safety reporting of a particular event. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB/EC/REB when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this protocol 
and local IRB/EC/REB 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 Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the device when it is used/operated by the subject. 
• 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. 

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• 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. 
• Discuss or review questionnaire responses with subjects and subsequently report adverse 
event(s) if warranted. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks 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. 
14.2.1. 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 ensuring 
competency of those to whom tasks are delegated as well as providing appropriate training to 
them, and adequate supervision of those to whom tasks are delegated. The Principal 
Investigator will provide both the training documents and a signed training log to BSC. Where 
there is a sub investigator at a site, the sub investigator should not be delegated the primary 
supervisory responsibility for the site. The investigator is accountable for regulatory violations 
resulting from failure to adequately supervise the conduct of the clinical study.  
14.3. Institutional Review Board/ Ethics Committee 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB/EC/REB for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 
A copy of the written IRB/EC/REB and/or competent authority (CA) approval of the protocol 
(or permission to conduct the study) and ICF, must be received by the sponsor before 
recruitment of subjects into the study. Prior approval must also be obtained for other materials 
related to subject recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/EC/REB before 
the changes are implemented to the study.  All changes to the ICF will be IRB/EC/REB 
approved; a determination will be made regarding whether a new ICF needs to be obtained 
from participants who provided consent, using a previously approved ICF.  

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Annual IRB/EC/REB approval and renewals will be obtained throughout the duration of the 
study as required by applicable local/country laws or regulations or IRB/EC/REB 
requirements. Copies of the study reports and the IRB/EC/REB continuance of approval must 
be provided to the sponsor.  
14.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
14.5. General Data Protection Regulations (GDPR) 
Data collected from clinical trial data subjects are considered “personal data” (including 
sensitive personal data in some cases). The protection of clinical trial subject personal data and 
compliance with privacy, data protection laws and regulations are of critical importance to 
BSC. Data collection has been carefully considered for this study and has been restricted to the 
strict essentials with a clear, specific and detailed purpose to mitigate the risk and the impact 
of data breach and to comply with data privacy laws (including but not limited to HIPAA and 
GDPR). Section 10 of the protocol defines the data that need to be collected to fulfill the 
objectives of the clinical study. 
 
Personal data collected by BSC includes, but is not limited to:  
• Geographic data (site name)  
• Important Dates  
o Informed consent date  
o Age at the time of study enrollment 
o Procedure date  
o Adverse event start/end date  
o Hospitalization admission/discharge date  
o Subject visit dates  
 
The purposes of the personal data processing will be carefully defined within the informed 
consent form. Personal data will not be used for a purpose other than the one stated in the 
informed consent provided to the subjects. Personal data shall not be disclosed, made available, 

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or otherwise used, processed, transferred, or stored for purposes other than those specified in 
the informed consent form, except: 
• with the consent of the data subject; or 
• processing is necessary for compliance with a legal obligation.  
 
14.5.1. Transparency 
BSC must only collect personal data by fair and lawful means. BSC must be transparent and 
open with individuals about how BSC collects and uses personal data, with whom BSC shares 
it, and where it may be processed. 
For this transparency principle, BSC must provide information to our health care providers and 
their study subjects about the purpose for collecting their personal data; who will have access 
to the data and to whom it may be shared, if it will be accessed or transferred to another country; 
and who to contact with questions or requests. 
14.5.2. Rights to Data Subjects 
In GDPR, a data subject is any living individual to whom the personal data relates. A data 
subject includes study subjects. Data subjects shall have the right to:  
• obtain from BSC confirmation of whether BSC has data relating to the individual; 
• have data relating to them communicated: 
o within a reasonable time (within 30 days from receipt of request, extendable if 
complicated or unclear request); 
o at a charge, if any, that is not excessive; 
o in a reasonable manner; and 
o in a form that is readily intelligible to the individual; 
• be given reasons if a request made under subparagraphs (a) and (b) is denied, and to be 
able to challenge such denial; 
• challenge data relating to the individual and, if the challenge is successful, to have the 
data erased, rectified, completed, or amended. During the period of such challenge, the 
individual can require that access to the data be restricted; 
• "opt out"/oppose that their personal data are used for marketing purposes; and, 
• when requested, BSC must also communicate any rectification or erasure of personal 
data or restriction of processing to each recipient to whom the personal data have been 
disclosed, unless this proves impossible or involves disproportionate effort. 
These rights will also be listed in the subject informed consent form. 
14.6. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC for 
subjects in the study will be obtained. 

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15. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements.  
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
16. Potential Risks and Benefits 
16.1. Instructions for Use 
Please refer to the Instructions for Use for an overview of anticipated adverse (device) effects, 
and risks associated to the commercial device(s).   
16.2. Risks associated with Participation in the Clinical Study 
The Flexiva Pulse and Flexiva Pulse ID Laser Fibers are commercially available devices. None 
of the procedures associated with this study fall outside of a standard of care procedure. 
Therefore, there are no foreseen additional risks associated with the procedure, testing, or 
withdrawal from the study. 
16.3. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject selection 
criteria, close monitoring of the subject's physiologic status during research procedures and/or 
follow-ups and by promptly supplying BSC with all pertinent information required by this 
protocol. 
16.4. Anticipated Benefits 
There are no guaranteed benefits from participation in this study. Potential benefits include 
stone clearance, improved urodynamics, and improved quality of life. The Flexiva Pulse and 
Flexiva Pulse ID Laser Fibers are commercially available devices and can be utilized with or 
without enrollment in this study. However, information gained from the conduct of this study 
may be of benefit to others with the same medical conditions.  

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Refer to the Instructions for Use for further information. 
17. Safety Reporting 
17.1. Reportable Events by investigational site to BSC 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories, from the time of Lithotripsy/HoLEP procedure to the end of the 
study: 
• Serious Adverse Device Effects (SADEs) 
• Procedure Related Serious Adverse Events (SAEs)  
• Fatal Serious Adverse Events (SAEs) 
• Adverse Device Effects (ADEs) 
• Procedure Related Adverse Events (AEs) 
• Device Deficiencies (including BSC devices used during the procedure) 
 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any reportable event must be recorded in the eCRF.  
The Investigator or designee is responsible for updating the eCRF with new and/or updated 
information in relation to the already reported event as soon as he/she becomes aware. 
 
Underlying diseases and chronic conditions are not reported as AEs unless there is an increase 
in severity or frequency during the course of the investigation. Death should not be recorded 
as an AE, but should only be reflected as an outcome of one (1) specific SAE (see Table 17.2-1 
for AE definitions). 
Refer to Instructions for Use for the known risks associated with the commercial device(s). 
17.2. Definitions and Classification 
Safety definitions are provided in Table 17.2-1. Administrative edits were made on the safety 
definitions from applicable regulations and guidance including (but not limited to) 21 CFR 
Part 812, ISO 14155 and EU MDR 2017/745/ MDCG 2020-10/1 Guidance on Safety 
Reporting in Clinical Investigations for clarification purposes. 
 

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Table 17.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, in the context of a clinical investigation, 
whether or not related to the study medical device and whether anticipated 
or unanticipated.  
NOTE 1: This includes events related to the study medical device or 
comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the study medical device. 
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
 
Adverse event related to the use of the study medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, 
the installation, the operation, or any malfunction of the study medical 
device. 
NOTE 2: This definition includes any event resulting from use error or 
from intentional misuse of the study medical device. 
NOTE 3: This includes ‘comparator’ if the comparator is a medical 
device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
 
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons 
as defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases, or  
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) fetal distress, fetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 

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Table 17.2-1: Safety Definitions 
Term 
Definition 
Ref: 21 CFR Part 812 
 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current risk assessment. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk assessment. 
Serious Health Threat 
 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an 
imminent risk of death or a serious deterioration in the health in subjects, 
users or other persons, and that requires prompt remedial action 
for other subjects, users or other persons. 
NOTE 1: This would include events that are of significant and unexpected 
nature such that they become alarming as a potential serious health hazard 
or possibility of multiple deaths occurring at short intervals. 
Device Deficiency 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
 
An inadequacy of a medical device related to its identity, quality, 
durability, reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and 
inadequacy in the information supplied by the manufacturer including 
labelling. 
NOTE 2: This definition includes device deficiencies related to the device 
under study or the comparator.  
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• 
emergency room visit that does not result in in-patient admission  
Note: although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria 
(e.g. medical or surgical intervention to prevent permanent 
impairment or damage) 
• 
elective and pre-planned treatment/surgery for a pre-existing 
condition that is documented in the subject’s record at the time of 
consent/enrollment 
• 
admission for social reasons and/or respite care in the absence of 
any deterioration in the subject’s general condition (e.g. subject is 
homeless, caregiver relief) 
• 
pre-planned, protocol-specified admission related to the clinical 
study (e.g. procedure required by protocol) 
Prolongation of hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
Note: new adverse events occurring during the hospitalization are 
evaluated to determine if they prolonged hospitalization or meet another 
SAE criteria. 

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17.3. Relationship to Study Device(s) (Device Under Study and Comparator Device, 
if applicable) and/or Study Procedure 
The Investigator must assess the relationship of the reportable AE to the study device(s), and/or 
study procedure. See criteria in Table 17.3-1:  
Table 17.3-1: Criteria for Assessing Relationship of Study Device(s) (Device Under 
Study and Comparator Device, if applicable) or Procedure to Adverse Event 
Classification 
Description 
Not Related 
Ref: MDCG 2020-10/1 
Relationship to the device, comparator or procedures can be excluded when: 
- the event has no temporal relationship with the use of the study device or the 
procedures related to the use of the study device; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ that cannot be affected by the device or 
procedure;  
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the study device used for 
diagnosis, when applicable;  
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Possibly Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device or comparator, or the relationship 
with procedures is weak but cannot be ruled out completely. Alternative causes are 
also possible (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment). Cases where relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
Probably Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the study device or, comparator, or the relationship 
with procedures seems relevant and/or the event cannot be reasonably explained by 
another cause. 

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Table 17.3-1: Criteria for Assessing Relationship of Study Device(s) (Device Under 
Study and Comparator Device, if applicable) or Procedure to Adverse Event 
Classification 
Description 
Causal Relationship 
Ref: MDCG 2020-10/1 
The serious event is associated with the study device, comparator or with 
procedures beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, 
when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 
 
17.4. Investigator Reporting Requirements 
The communication requirements for reportable events to BSC are as shown below. 
Table 17.4-1: Investigator Requirements for Reporting 
Event Classification 
Communication Method  
Communication Timeline post-market 
studies  
(EU MDR 2017/745, MDCG 2020-
10/1MEDDEV 2.12/1:  Guidelines on a 
Medical Device Vigilance System) 
Unanticipated Adverse 
Device Effect / Unanticipated 
Serious Adverse Device 
Effect  
 
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 1 business day of first becoming 
aware of the event.  
• 
Terminating at the end of the study. 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
Upon request of sponsor.  

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Event Classification 
Communication Method  
Communication Timeline post-market 
studies  
(EU MDR 2017/745, MDCG 2020-
10/1MEDDEV 2.12/1:  Guidelines on a 
Medical Device Vigilance System) 
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 10 calendar days after becoming 
aware of the event or as per local/regional 
regulations.  
• 
Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
When documentation is available 
• 
Upon request of sponsor 
Serious Adverse Device 
Effects 
Complete AE eCRF page 
with all available new and 
updated information. 
• 
Within 3 calendar days of first becoming 
aware of the event or as per local/regional 
regulations. 
• 
Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
When documentation is available 
• 
Upon request of sponsor 
Device Deficiencies 
(including but not limited to 
malfunctions, use errors, and 
inadequacy in information 
supplied by the manufacturer, 
including labelling) 
Note:  Any Device Deficiency 
that might have led to a 
serious adverse event if 
appropriate action had not 
been taken, intervention had 
not occurred, circumstances 
had been less fortunate is 
considered a reportable event. 
Complete Device 
Deficiency eCRF with all 
available new and updated 
information.  
• 
Within 3 calendar days of first becoming 
aware of the event. Reporting required 
through the end of the study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event. 
• 
Upon request of sponsor  
Adverse Event including 
Adverse Device Effects 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• 
Adverse Device Effects (or other key 
events of interest, e.g., Heart Failure): In 
a timely manner but not later than 30 
business days after becoming aware of the 
information  
• 
Adverse Events: In a timely manner but 
recommend within 30 business days after 
becoming aware of the information 
• 
Reporting required through the end of the 
study  
• 
Upon request of sponsor 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  

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17.5. BSC Device Deficiencies 
Device deficiencies will be collected for BSC devices only and will be documented and 
reported to BSC. If possible, the device(s) should be returned to BSC for analysis. Instructions 
for returning the device(s) will be provided by the Clinical Project Manager. Device 
deficiencies should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency, would be recorded as an adverse event on the appropriate eCRF. 
17.6. Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs/ECs/REBs and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC/REB, and regulatory 
authorities of UADEs and SAEs as required by local/regional regulations. 
17.7. Subject Death Reporting  
A subject death during the study should be reported to BSC as soon as possible and, in any 
event, within three (3) calendar days of site notification. The site’s IRB/EC/REB must be 
notified of any deaths in accordance with that site’s IRB/EC/REB policies and procedures. 
Notification of death must include a detailed narrative (death letter) that provides detailed 
information describing the circumstances surrounding the death. A death narrative in the local 
language is acceptable, if accompanied by a translation in English. The details listed below 
should be addressed in the death narrative, in order for BSC to understand the circumstance 
surrounding the death:  
• Date of death 
• 
Immediate cause of death 
• 
Whether the death was related to the device or to the procedure 
• 
Any other circumstances surrounding the death 
• 
Investigator or sub-investigator signature and date 
Also submit the following documentation: 
• 
If the patient expired in the hospital: 
o A copy of the medical records for that admission (e.g., History and Physical, 
consults, test results, operative reports, and/or progress notes from the hospital 
chart) 
o Death certificate (if available) 
o Autopsy report (if applicable and available) 
• 
If the patient expired outside of the hospital (e.g., home): 
o A copy of the most recent clinic visit (if not already submitted to BSC) 

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o Death certificate (if available) 
The Clinical Events Committee (CEC) will review information regarding subject deaths. 
18. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or subject’s legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any study devices, study-required 
procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC/REB, or central IRB, if 
applicable. 
BSC will provide a study-specific template of the ICF to investigators participating in this 
study. The ICF template may be modified to meet the requirements of the investigative site’s 
IRB/EC/REB.  Any modification requires acceptance from BSC prior to use of the form.  The 
ICF must be in a language understandable to the subject and if needed, BSC will assist the site 
in obtaining a written consent translation. Translated consent forms must also have 
IRB/EC/REB approval prior to their use.  Privacy language shall be included in the body of 
the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, as 
well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or subject’s 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed consent 
process. If a legal representative signs, the subject shall be asked to provide informed consent 
for continued participation as soon as subject’s medical condition allows. The original signed 

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ICF will be retained by the site and a copy of the signed and dated document and any other 
written information must be given to the person signing the form.  
Failure to obtain subject consent must be reported to BSC. Any violations of the informed 
consent process must be reported as deviations to the sponsor and local regulatory authorities 
(e.g. IRB/EC/REB), as appropriate. 
If new information becomes available that can significantly affect a subject's future health and 
medical care, that information shall be provided to the affected subject(s) in written form via 
a revised ICF or, in some situations, enrolled subjects may be requested to sign and date an 
addendum to the ICF. In addition to new significant information during the course of a study, 
other situations may necessitate revision of the ICF, such as if there are amendments to the 
applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC/REB. The new version of the ICF must be approved 
by the IRB/EC/REB. Acceptance by BSC is required if changes to the revised ICF are 
requested by the site’s IRB/EC/REB. The IRB/EC/REB will determine the subject population 
to be re-consented. 
19. Committees 
19.1. Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operations group review safety 
data as it is reported by the sites throughout the duration of the study. During scheduled 
monitoring activities, clinical research monitors further support this review through their 
review of source documents and other data information. The BSC Medical Safety and Safety 
Trial Operations team include health care providers with the necessary therapeutic and subject 
matter expertise to evaluate and classify the events into the categories outlined above. 
19.2. Clinical Events Committee 
Adjudication of clinical events will be performed by an independent physician or group of 
physicians with pertinent expertise. Independent physician(s) will review and adjudicate 
important endpoints and relevant adverse events reported by study investigators. Independent 
physician(s) will review a safety event dossier, which may include copies of subject source 
documents provided by study sites. 
Membership will include practitioner(s) of urology with the necessary therapeutic and subject 
matter expertise to adjudicate important endpoints and relevant adverse events reported by 
study investigators. Adjudication responsibilities, qualifications, membership, and 
adjudication procedures are outlined in the adjudication charter. The adjudication charter will 
also specify the stage at which adjudication activities will cease and events will be reviewed 
internally by BSC.  

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20. Suspension or Termination 
20.1 Premature Termination of the Study 
BSC reserves the right to terminate the study at any stage but intends to exercise this right only 
for valid scientific or business reasons and reasons related to protection of subjects.  
Investigators, associated IRBs/ECs/REBs, and regulatory authorities, as applicable, will be 
notified in writing in the event of study termination. 
20.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the sponsor 
shall suspend the clinical investigation while the risk is assessed. The sponsor shall 
terminate the clinical investigation if an unacceptable risk which cannot be controlled is 
confirmed. 
• Instructions by the IRB/EC/REB or regulatory authorities to suspend or terminate the 
clinical investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of BSC to suspend or discontinue development/marketing of the 
device. 
20.2 Termination of Study Participation by the Investigator or Withdrawal of IRB/ 
EC/REB Approval 
Any investigator, or associated IRB/EC/REB or regulatory authority may discontinue 
participation in the study or withdraw approval of the study, respectively, with suitable written 
notice to BSC. Investigators, associated IRBs/ECs/REBs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
20.3 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating sites by BSC. The IRB/EC/REB 
and regulatory authorities, as applicable, will be notified. Detailed information on how enrolled 
subjects will be managed thereafter will be provided.  
In the event an IRB/EC/REB terminates participation in the study, participating investigators, 
associated IRBs/ECs/REBs, and regulatory authorities, as applicable, will be notified in 
writing. Detailed information on how enrolled subjects will be managed thereafter will be 
provided by BSC. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
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to transfer Principal Investigator responsibility; detailed information on how enrolled subjects 
will be managed thereafter will be provided by BSC. 
The Principal Investigator or designee must return all study-related documents and devices, if 
supplied by BSC, unless this action would jeopardize the rights, safety, or welfare of the 
subjects. 
20.4 Criteria for Suspending/Terminating a Study Site 
BSC reserves the right to stop the inclusion of subjects at a study site at any time after the study 
initiation visit if no subjects have been enrolled for a period beyond 6 months after site 
initiation, or if the site has multiple or severe protocol violations/noncompliance without 
justification and/or fails to follow remedial actions. 
In the event of termination of site participation, all devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB/EC/REB and regulatory authorities, as applicable, will be 
notified. Study participants will be contacted, as applicable, and be informed of changes to 
study visit schedule. 
21. Study Registration and Results 
21.1. Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
21.2. Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the BSC Policy. A Clinical Investigation 
Report will be made available to all investigators, IRB/EC/REB and regulatory authorities, as 
applicable in accordance with the BSC Policy and local requirements.  As applicable an 
abbreviated Clinical Investigation Report will be made available on a publicly accessible 
database. 
21.3. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC may submit study results 
for publication (regardless of study outcome) following the conclusion or termination of the 
study. BSC adheres to the Contributorship Criteria set forth in the Uniform Requirements of 
the International Committee of Medical Journal Editors (ICMJE; http://www.icmje.org). In 
order to ensure the public disclosure of study results in a timely manner, while maintaining an 
unbiased presentation of study outcomes, BSC personnel may assist authors and investigators 
in publication preparation provided the following guidelines are followed:  

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• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should be 
discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the BSC Data Sharing Policy 
(https://www.bostonscientific.com/).  
22. Bibliography 
1 
Erhard MJ, Bagley DH , 1995; Floratos DL, 1999; Shigemura K, 2018; 
Kronenberg P 2015 
2 
Turk C, Petrik A, Sarica K, et al. EAU Guidelines on Diagnosis and 
Conservative Management of Urolithiasis. Eur Urol. 2016;69(3):468-474 
3 
Chew BH, Lange D. The future of ureteroscopy. Minerva Urol Nefrol. 
2016;68(6):592-597 
4 
Fried NM, Irby PB. Advances in laser technology and fibre-optic delivery 
systems in lithotripsy. Nat Rev Urol. 2018;15(9):563-573 
5 
Sabler IM, Katafigiotis I, Gofrit ON, Duvdevani M. Present indications and 
techniques of percutaneous nephrolithotomy: What the future holds? Asian J 
Urol. 2018;5(4):287-294 
6 
Nimeh T, Magnan B, Almallah YZ. Benign Prostatic Hyperplasia: Review of 
Modern Minimally Invasive Surgical Treatments. Semin Intervent Radiol. 
2016;33(3):244-250 
7 
Aldoukhi AH, Roberts WW, Hall TL, Ghani KR. Holmium Laser 
Lithotripsy in the New Stone Age: Dust or Bust? Front Surg. 2017;4:57. 
8 
Chew BH, Lange D. The future of ureteroscopy. Minerva Urol Nefrol. 
2016;68(6):592-597 
9 
Knudsen BE. Laser Fibers for Holmium:YAG Lithotripsy: What Is 
Important and What Is New. Urol Clin North Am. 2019;46(2):185-191 
10 
Shigemura K, Fujisawa M. Current status of holmium laser enucleation of the 
prostate. Int J Urol. 2018;25(3):206-211. 
 

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23. Abbreviations and Definitions  
23.1. Abbreviations 
Abbreviations are shown in Table 23.1-1  
Table 23.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AT 
As Treated 
BPH 
Benign Prostatic Hyperplasia 
BPO 
Benign Prostatic Obstruction 
BSC 
Boston Scientific Corporation 
CA 
Competent Authority 
CBC 
Complete Blood Count 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CT 
Computed Tomography 
EAU 
European Association of Urology 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ESWL 
Extracorporeal Shock Wave Lithotripsy 
EU 
European Union 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GDPR 
Global Data Protection 
H & P 
History and Physical 
HIPAA 
Health Information Portability and Accountability Act 
HoLEP 
Holmium Laser Enucleation of the Prostate 
Ho: YAG 
Holmium: yttrium-aluminum-garnet Laser 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IFU 
Instructions For Use 
INR 
International Normalized Ratio 
IPSS 
International Prostate Symptom Score 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intent To Treat 
LUTS 
Lower Urinary Tract Symptoms 

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Table 23.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
MET 
Medical Expulsive Therapy 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PCNL 
Percutaneous Nephrolithotomy Procedures 
PP 
Per Protocol 
PSA 
Prostate-Specific Antigen 
PT 
Prothrombin Time 
PTT 
Patrial Thromboplastin Time 
PUL 
Prostatic Urethral Lift 
PVR 
Post Void Residual 
QOL 
Quality of Life 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SFR 
Stone Free Rate 
SOC 
Standard of Care 
TUIP 
Transurethral Incision of Prostate 
TURP 
Transurethral Resection of Prostate 
UADE 
Unanticipated Adverse Device Effects 
UPN 
Universal Product Number 
USADE 
Unanticipated Serious Adverse Device Effects 
UTI 
Urinary Tract Infection 
23.2. Definitions 
Terms are defined in Table 23.2-1.  
Term 
Definition 
Adverse Device Effect 
(ADE) 
See Table 17.2-1: Safety Definitions 
Adverse Event (ADE) 
See Table 17.2-1: Safety Definitions 
As Treated 
All subjects for whom treatment is attempted. 
Clinical Events Committee 
An independent or group of physicians with trial relevant therapeutic 
expertise whose purpose is to review and adjudicate important endpoints 
and/or specific adverse events. 
Data Subject 
In GDPR: Any living individual to whom the personal data relates. Examples 
of data subjects in this study are physicians and subjects. 
Table 23.2-1: Definitions 

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Term 
Definition 
Deviation (Clinical Protocol) 
A departure from the requirements established in the clinical trial protocol 
(e.g., inclusion/exclusion criteria; visit windows, required procedures, and 
any specified consenting process requirements). 
Device Deficiency 
See Table 17.2-1: Safety Definitions 
General Data Protection 
Regulation (GDPR) 
The General Data Protection Regulation (GDPR) is a European law that will 
govern how companies (whether EU-based or not) use personal data. 
Hospitalization 
See Table 17.2-1: Safety Definitions 
Intent-To-Treat 
A subject who signs the informed consent, meets eligibility criteria, and for 
whom the Lithotripsy/HoLEP procedure is initiated but not completed (first 
incision). The original ICF and screening documentation for intent to treat 
patients should be maintained in the site’s files. These patients are followed 
in accordance with the study follow up schedule for safety and count toward 
enrollment.   
Monitoring 
EN ISO 14155:2020-3.29 - Act of overseeing the progress of a clinical 
investigation to ensure that it is conducted, recorded, and reported in 
accordance with the CIP, written procedures, this document, and the 
applicable regulatory requirements. 
ICH E6 1.38 - The act of overseeing the progress of a clinical study and of 
ensuring that it is conducted, recorded, and reported in accordance with the 
protocol, Standard Operating Procedures (SOPs), GCP, and the applicable 
regulatory requirement(s). 
FDA Guidance - Generally refers to the methods used by sponsors of 
investigational studies, or CROs delegated responsibilities for the conduct of 
such studies, to oversee the conduct of and reporting of data from clinical 
investigations, including appropriate investigator supervision of study site 
staff and third-party contractors. 
Multi-center study 
A clinical trial conducted according to a single protocol but at more than one 
site, and therefore carried out by more than one investigator. 
Per Protocol 
All subjects in the As Treated Population who have no major protocol 
deviations. 
Personal Data  
GDPR defines “Personal data” to be any information relating to an identified 
or identifiable natural person (‘data subject’); an identifiable natural person 
is one who can be identified, directly or indirectly, in particular by reference 
to an identifier such as a name, an identification number, location data, an 
online identifier or to one or more factors specific to the physical, 
physiological, genetic, mental, economic, cultural or social identity of that 
natural person. 
Point of Enrollment 
Time at which, following recruitment, a subject signs and dates the informed 
consent form 
Processing 
Any use of personal data by BSC (or a third party on behalf of BSC), 
including data collection, data sharing, anonymization, and data storage (note 
the mere storage of data is considered as processing). 

Form/Template 92120219 Rev/Ver F 
Confidential 
 Flexiva Pulse Registry – U0703, 92704912 Rev/Ver A 
Page 59 of 59 
 
  
Term 
Definition 
RAVE 
Proprietary electronic data capture system for capturing, managing and 
reporting clinical study data. 
Recruitment 
Active efforts to identify subjects who may be suitable for enrollment in the 
clinical investigation. 
Sensitive Personal Data 
GDPR defines “Sensitive personal” data as a subset of Personal Data, which, 
due to their nature have been classified as deserving additional privacy and 
security protections because their processing may create a risk for an 
individual’s fundamental right and freedom. 
Serious Adverse Device 
Effect (SADE) 
See Table 17.2-1: Safety Definitions 
Serious Adverse Event 
(SAE) 
See Table 17.2-1: Safety Definitions 
Site Noncompliance 
A departure from the regulations established by the relevant regulatory 
authorities. Includes all clinical site noncompliance that does not represent a 
direct deviation from the clinical trial protocol, e.g. IRB/IEC and sponsor 
reporting, device storage and accountability, staff qualifications and training, 
facilities, and equipment required to conduct the clinical trial, collection and 
documentation of data in source documents and CRFs, investigator 
oversight, etc. 
Source Document 
Original or certified copy of printed, optical or electronic document 
containing source data (Ref. ISO 14155-2020)