Randomized Clinical Trial Evaluating the Efficiency and Safety of Holmium Laser With Moses Technology Versus SuperPulsed Laser System With Thulium Laser on Renal and Ureteral Stones
Phase: PHASE4
Conditions: Urinary Tract Stone
Sponsor: University of Wisconsin, Madison

NCT04963062 
Protocol 2021-0695 
 
 
 
 
 
 
 
 
Randomized Clinical Trial Evaluating the Efficiency and 
Safety of Holmium Laser with Moses Technology versus 
SuperPulsed Laser System with Thulium Laser on Renal 
and Ureteral Stones 
 
Principal Investigator: Stephen Nakada, MD 
Co-Investigator: Margaret Knoedler, MD; Shuang Li, PhD; Kristina Penniston, PhD 
Affiliation: University of Wisconsin-Madison, School of Medicine and Public Health, 
Department of Urology 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NCT04963062 
Protocol 2021-0695 
PROTOCOL TITLE: 
Randomized Clinical Trial Evaluating the Efficiency and Safety of Holmium Laser with Moses 
Technology versus SuperPulsed Laser System with Thulium Laser on Renal and Ureteral Stones 
 
LEAD RESEARCHER: 
PI: Stephen Nakada, MD nakada@urology.wisc.edu 
Co-Investigators 
Margaret Knoedler, knoedler@urology.wisc.edu 
Shuang Li; lis@urology.wisc.edu  
Kristina Penniston, penn@urology.wisc.edu 
Sarah Best: best@urology.wisc.edu 
Sean Hedican: hedican@urology.wisc.edu 
 
VERSION NUMBER/DATE: 
Version 3, 8/30/2021 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
6/14/2021 
Initial IRB review modification requests 
Yes 
2 
7/22/2021 
Change of protocol  
No  
3 
8/30/2021 
Change of protocol 
No  
 
 
 
 
 
 
 
 

NCT04963062 
Protocol 2021-0695 
Project Summary 
This is a prospective randomized controlled trial designed to assess the efficiency of 
Lumenis® Pulse™ P120H holmium laser system with the Moses technology (holmium laser with 
Moses) versus the Soltive™ SuperPulsed Laser System with the thulium fiber laser technology 
(thulium laser), in fragmentation of upper tract urinary stones during ureteroscopy with laser 
lithotripsy. Specifically, we will compare procedural time, intra-operative parameters and stone 
free rates. Laser lithotripsy is a surgical procedure performed during stone surgeries. Both 
lasers are FDA approved and clinically used in the United States. Currently, at University of 
Wisconsin, we are using the holmium laser with Moses during ureteroscopies and we will soon 
have the thulium laser for clinical use as well. At our institution, we perform approximately 200 
outpatient ureteroscopies with laser lithotripsy annually. Typically, we have evaluated surgical 
outcomes as part of routine quality improvement initiatives or as IRB-approved retrospective 
reviews. However, in this scenario, a randomized trial requiring IRB approval, we have the 
ability to conduct a higher-level study protocol and rigorously compare the time required for 
acceptable stone fragmentation using the two different lasers. A randomized trial, unlike a 
retrospective review of our surgical procedures, will reduce bias sufficiently to allow us to be 
sure of our results. 
 
Number of Study Sites 
UW, Department of Urology only 
Background and Significance 
The incidence of urinary tract stone disease is increasing. According to the National 
Health and Nutrition Examination Survey, as of 2012, 10.6% of men and 7.1% of women in the 
United States are affected by renal stone disease.i This has led to an increased demand on 
Urologists for efficient and safe surgical treatment of stone disease. Over the past two decades, 
ureteroscopy with laser lithotripsy has become the treatment of choice for most ureteral and 
renal stones globally.ii The holmium laser is considered the gold standard for laser lithotripsy.iii 
Holmium laser lithotripsy with Moses and the thulium laser are new technologies meant to 
improve the efficiency of laser lithotripsy. Both are FDA approved treatment modalities for 
stone disease. Two in vitro studies have compared Moses versus thulium and shown that 
thulium has higher ablative volumes then the holmium laser with Moses, but no clinical trials 
have compared the two treatment modalities.iv,v In this study, we are going to conduct a 
prospective, randomized clinical trial to determine whether there is a difference in procedural 
time, intraoperative parameters or stone free rate between the Holmium laser with Moses and 
the thulium laser. This is significant as this may lead to shorter overall operative times, which 
may result in decreased operative costs and complications. vi,vii 

NCT04963062 
Protocol 2021-0695 
Study Objectives 
The primary objective of this study is to compare the procedural time to acceptable 
stone fragmentation during clinical use of the holmium laser with Moses and the thulium laser. 
Our hypothesis is that the thulium laser will have decreased procedural time compared to the 
holmium laser with Moses. Secondary outcomes will include intra-operative parameters and 
post-operative parameters. Our clinical practice is to treat urinary stones until the stone is 
reduced to fragments ≤ 2 mm in size. This is determined by using the laser fiber (A 200 micron 
fiber will be used with both groups), to visually estimate the size of the resultant fragments.viii  
The secondary objective is to compare the primary and secondary outcomes when 
stratified by stone size. This will allow us to explore the efficiency between Moses and thulium 
laser on treating large vs. small stones. Previous literature suggested that stone size was 
associated with operative time.ix Patients will be separated based on the size of their stones: 3-
10 mm or 11-20 mm and then randomized to holmium laser with Moses or thulium laser. 
Patients will be randomized into the groups by a ratio of 1:1. 
Research Design and Methods 
This study will be a randomized trial comparing ureteroscopy with laser lithotripsy with 
the Lumenis® Pulse™ P120H holmium laser system with the Moses technology (holmium laser 
with moses) versus the Soltive™ SuperPulsed Laser System with the thulium fiber laser 
technology (thulium laser). The primary objective is to compare the procedural time (minutes). 
We will keep strict timing from the minute the ureteroscope is inserted into the patient to the 
time the ureteroscope has been removed. The following information will be collected as 
secondary outcomes: (1) stone free rate; (2) total operative time (minutes); (3) 
fragmentation/dusting time (minutes, total time to fragment the stone, including the laser was 
in use and time of pedal pauses); (4) lasing time (minutes, time the laser was in use, not 
including pedal pauses); (5) total energy used (kilojoules, kJ); (6) laser efficiency (mm per 
minute); (7) number of times the laser pedals are pressed (left, right, and total pedal presses); 
(8) stone analysis; (9) complications; (10) quality of life survey (WISQOL short form) both pre-
operatively and post-operatively and (11) physician evaluation of the laser. Physicians will 
complete a one page survey at the end of the case evaluating the laser (survey included as 
attachment). A total of 3 clinic visits (i.e., pre-operative visit, the stone surgery, and one post-
operative visit) will be needed for this study. Stone parameters (i.e. size, location, Hounsfield 
units, presence of hydronephrosis, stone volume), demographic information, co-morbidities, 
and post-operative parameters will be collected from the medical record.  
Number of Participants  

NCT04963062 
Protocol 2021-0695 
Approximately 164 patients will be enrolled (see Data Analysis for sample size 
justification).  
Inclusion Criteria 
1. Patients at least 18 years of age, and less than 89 years old. 
2. Patients with renal or ureteral urinary stones who require endoscopic treatment in 
the outpatient operating room 
3. Patients’ stone size in a single renal unit of 3-10 mm and 11-20 mm. Stone size is 
defined as the largest diameter of a single stone on pre-operative CT. Patients with 
multiple stones will be included as long as their largest stone size falls within the 
above parameters.  
Exclusion Criteria 
1. Patients under 18 years of age and over 89 years old.  
2. Pregnant patients 
3. Patients with transplant kidneys 
4. Patients with irreversible coagulopathy 
5. Patients with known ureteral stricture disease 
6. Patient who do not have a pre-operative CT.  
7. Non-English speaking, vulnerable patients such as lacking of decision-making 
capability, prisoner, adult unable to consent, will not be enrolled.  
Recruitment methods 
Patients who are to be scheduled for laser lithotripsy treatment of urinary stones as outpatients 
will be approached for study participation. During patients’ pre-operative clinic visit, eligibility 
screening (by reviewing patients’ medical record that is relevant for inclusion/exclusion criteria) 
will occur before recruitment. If patients meet the inclusion criteria, they will be initially 
approached by a study team member who also works in the urology clinic (i.e., the surgeon 
informs the patient that there’s a research study they may be eligible for, and asked if they 
want to learn more about it).   
 
No other recruitment materials will be used in this study. Holmium laser with Moses or thulium 
laser to treat stones is our routine care. Patients have been informed about the laser lithotripsy 
treatment before they schedule their surgery. We will only recruit patients from the outpatient 
OR, so this will not include patients who come in emergently through the Emergency 
Department.  
 

NCT04963062 
Protocol 2021-0695 
No compensation will be provided to participants.  
 
 
Consent Process 
A study team member who is affiliated with the patient’s clinical care (e.g., the surgeon) will 
initially approach the patients who are scheduled for laser lithotripsy treatment of urinary 
stones. (i.e., informed that there’s a research study they may be eligible for, and asked if they 
want to learn more about it). 
If the patient is interested in the study, a member of the research team will approach him/her 
for enrollment. Consent process will be conducted face to face. Participants will be provided a 
written consent form in person. No waiting time is expected between informing the prospective 
participant and obtaining the consent. 
Consent will take place during patients’ pre-operative clinic visit. If patients are 
interested and there is not enough time to consent the patient in urology clinic, study 
information will be sent home with the patient and the patient will then be consented 
before their surgery in a private room (pre-operative room). Pre-operative room 
provides 1-1 1/2 hours of time. This should be ample time to conduct the consent 
process before surgery anesthesia. 
All information about the study will be provided, and ample time will be made available 
for the participants to consider participation in the study.  
 
Patient Randomization  
Patients will be randomized (ratio 1:1) at the time of enrollment to be treated with either the 
holmium laser with Moses or the thulium laser. We will use Permuted Block Randomization 
(stratified by stone size 3 - 10 mm or 11-20 mm) (block size 4).  
 
Study Procedures 
1. The study team members review patients’ medical record during patients’ pre-
operative clinic visit to see whether patients meet inclusion/exclusion criteria.  
2. If patients meet the inclusion criteria, a study team member who is affiliated with 
the patient’s clinical care (e.g., the surgeon) will initially approach the patients who 
are scheduled for laser lithotripsy treatment of urinary stones. (i.e., informed that 
there’s a research study they may be eligible for, and asked if they want to learn 
more about it). 
3. If the patient is interested in the study, a member of the research team will 
approach him/her for enrollment. 
4. Patients will be asked to fill out a WISQOL short form at their pre-operative visit. 
This is standard of care for all stone patients in clinic.  

NCT04963062 
Protocol 2021-0695 
5. Patients’ total stone size (pre-operative CT) will be calculated and divided into two 
groups. Those with stones 3-10 mm and those with stones 11-20 mm. They will then 
be randomized to either the holmium laser with Moses or the thulium laser 
(randomization ratio 1:1) group.  
6. Patients will undergo stone surgeries with the laser that they are randomized to. A 
200 micron fiber will be used with both machines. The patient’s stone(s) will be 
treated in accordance with our routine clinical practice of fragmenting stone into 
small pieces (≤ 2mm). One stone fragment will be collected for stone analysis if the 
patient does not already have a stone analysis on file (this is also standard of care). 
The faculty surgeons will perform all surgeries. We are unable to blind the surgeon 
to the laser used as the laser fibers and laser machines appear and sound different. 
7. Procedural time as well as other information (see study design for the detail 
information) is collected. 
8. After surgery, the patients will all have at least an abdominal x-ray within 1 month of 
surgery, if a CT scan has not already been completed(this is the standard of care). 
They will also be asked to fill out a WISQOL short form at their one-month follow up 
appointment. Otherwise, they will continue on our normal postoperative pathway. 
Postoperative complications will be collected. 
 
Comparison of usual care and study procedures 
 
Compared with our routine care, the only interventions imposed on subjects as a result 
of this study are (1) pre-procedural randomization to laser lithotripsy with either holmium laser 
with Moses or thulium laser, and (2) the use of patient & surgery information collected in 
describing our results. All the other activities are part of our routine clinical practice. 
Participation in the study will require a pre-operative CT abdomen without contrast, which is 
standard of care, as well as at least an abdominal x-ray post operatively which is also standard 
of care. Four surgeon will perform the ureteroscopy (i.e., Nakada, Best, Hedican, Gralnek, and 
Knoedler). During surgery, patients’ stones will be treated in accordance with our routine 
clinical practice of fragmenting stones into small pieces (<2 mm). Surgeons will use a 200 
micron fiber for both the holmium laser with Moses and the thulium laser, but they will have 
the discretion to switch to a different fiber (ex. 150 micron thulium fiber) if they feel it is 
necessary during the case (if the surgeon changes the fiber during the surgery, the data will be 
analyzed separately). A stone fragment will be collected for stone analysis if the patient does 
not have one on file. This is our standard of care suggested by AUA guideline.x All patients 
enrolled will undergo routine post-operative follow up including clinic appointments and 
imaging evaluation (with at least an abdominal x-ray). An abdominal x-ray is used for follow up 
of nephrolithiasis and provides significantly less radiation, and it is our routine care. However, if 
the patient already has a CT completed by the follow-up visit, an x-ray is not needed.  
WISQOL short form will be administered during the pre-operative appointment and at the post-
operative appointment, which is standard practice in our clinic.  

NCT04963062 
Protocol 2021-0695 
 
Withdrawal of participants 
 
Patients can withdraw anytime. Once they decide to withdraw, they will continue their 
standard clinical care with us. We will continue to collect patients’ information from 
patients’ medical records for their routine medical care.  
 
Study Intervention 
 
Holmium laser with Moses and thulium lasers will be used for this study. Both are FDA 
approved lasers for the treatment of urinary calculi through an endoscope. The holmium laser 
with Moses emits two separate laser pulses with a short time interval between them. The first 
pulse divides the water between the laser fiber tip and the stone and the second pulse hits the 
stone unobstructed.xi The goal is to increase stone ablative volume and decrease retropulsion 
of the stone. The thulium laser has a different wavelength then the holmium laser with Moses 
and thus has slightly different energy properties. It has also been shown to increase ablative 
volume and decrease retropulsion without any safety concerns.xii The holmium laser with 
moses is currently the most common laser used at our institution for treatment of urinary 
stones. The thulium laser has been used at our institution on a trial basis previously and will be 
available soon for use on a daily basis for surgical cases at our institution. There is no learning 
curve associated with the thulium laser. The two lasers have similar specifications; the two 
fibers are the same size and will interact with the instruments (ureteroscopes) similarly. 
Study Timelines 
For each patient, the study duration is from consent to the one-month post-operative 
clinic visit. Patients will be on study for approximately 6-8 weeks. 
Risks and Potential Benefits 
Treatment with the holmium laser with Moses and thulium laser can be associated with 
the common risks of hematuria, stent pain, passing fragments, UTI, dysuria. The rare 
risks include perforation of the urinary tract, bleeding, and stricture of the ureters. 
However, the surgeon who will perform the surgery will not exceed safe levels. All 
procedures performed by surgeons who are board-certified. If significant injury or 
inefficient fragmentation of the stone occurs, the surgeon will have the discretion to 
transition to a different laser for patient safety reasons. All patients enrolled will 
undergo routine post-operative follow up including clinic appointments and imaging 
evaluation. Any complications will be recorded, reported, and treated appropriately. 
There is a risk that your information could become known to someone not involved in 
this study, which might make you uncomfortable.   

NCT04963062 
Protocol 2021-0695 
There is no direct benefit. Potentially, more efficient laser may be identified which may 
result in faster procedural time and lower complication rates.  
Safety Monitoring Plan 
 
All procedures performed by surgeons who are board-certified. If significant injury or 
inefficient fragmentation of the stone occurs, the surgeon will have the discretion to transition 
to a different laser for patient safety reasons (The data will be analyzed as an intention-to-treat 
analysis). All patients enrolled will undergo routine post-operative follow up including clinic 
appointments and imaging evaluation. Any complications will be recorded, reported, and 
treated appropriately. 
Regular inquiries of study flow, pertaining to patient recruitment, randomization, and 
adverse events will be scheduled to occur after the first week and subsequently every two 
weeks. The lead researcher, Dr. Nakada, will be responsible for the inquiries.  Any adverse 
events will be monitored as per standard protocol in clinical use. A comparison of adverse 
events between groups (e.g., to determine whether those assigned to the thulium laser group 
are experiencing more frequent or serious adverse effects) will be included. No significant 
adverse events are anticipated for the lasers, as they are routinely used in urology practice.  
Any adverse events or unanticipated problems will be reported to the PI and IRB and treated 
accordingly. In addition, members of the study team will be performing these procedures and 
will monitor the patient during treatment for any signs of complications. 
 
Date Management and Confidentiality  
 
All electronic data will be stored on a HIPAA compliant department server which is maintained 
on password and firewall-protected computers in locked offices of the Department of Urology, 
located in a security-protected building. Data to be analyzed after extraction. All paper records 
(such as WISQOL) will be saved in a locked office/cabinets of IRB approved study staff. Only key 
personnel listed on this study will have access to this information. All data analysis files will be 
devoid of direct patient identifiers. Direct identifiers will be destroyed at study closure or at the 
time of publication. De-identified data will be stored for potential future studies that have 
proper approval. 
 
Since we have 5 surgeons participating in this study, we will use university-based cloud service 
(such as OneDrive) to temporarily save the enrollment log. Study team member will use their 
Net ID to access the enrollment log. The enrollment log is completely deidentified. Only 
participant ID (such as 101, 102) and the laser each participant is randomized to are saved in 
the enrollment log. Once we complete data collection, we will permanently delete it from the 
cloud.  
 
Share of results 

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Protocol 2021-0695 
Some of the information collected for this study will go in the patient’s medical record. 
This includes the results of the one-month post-operative image, stone analysis, stone 
surgery, and all clinic visits information as these are being conducted as standard of 
care. All other information from research specific procedures will NOT go in the 
patient’s medical records.  
We only publish aggregated results. No individual results will be shared. We will not 
share the data with outside institutions.  
 
Economic burden to participants 
This study does not place financial burden to patients. The study interventions are our 
routine clinical practice to treat stones. It will be same as they are not involved in this 
study.  
The cost of the two laser treatments are equivalent.  
 
Data Analysis 
The data collected will be analyzed as an intention-to-treat analysis. Statistical analyses 
will include T-test and, if appropriate, Chi-square tests (e.g., for categorical data), and two-way 
MANOVA. Patient demographics and stone characteristics will be summarized as appropriate as 
continuous variables (mean and standard deviation) or categorical variables (frequency, 
percentage). To compare the two groups, continuous variables such as procedural time, total 
OR time, WISQOL etc., will be analyzed using T test and two-way MANCOVA (stratified by stone 
size 3 - 10 mm or 11-20 mm). The surgeon will be controlled as a covariate. Categorical 
variables such as stone free rate will be analyzed using chi-square.  
We plan to enroll 164 patients in this study. Patients will be stratified into two groups 
according to their stone size (3-10 mm or 11-20 mm) and then randomized to either holmium 
laser with Moses or thulium laser. The stone size is defined as the largest stone size (largest 
diameter on pre-operative CT), if patients have multiple stones.  Previous literature suggested 
stone size is associated with operative time.ix A significance level of 0.05 will be used with a 
two-sided two-sample equal-variance t-test. Group sample sizes of 33 and 33 achieve 80% 
power to detect a significant difference between the means when the mean difference is 4.6 
minutes with a standard deviation of 6.5 minutes. We also decide to increase the sample size 
by 25% (41 patients per group). This will allow for the possibility that the randomization scheme 
is intra-operatively abandoned for some reason (e.g., equipment failure), that the planned 
procedure was unable to be completed for some reason, as determined by the surgeon in 

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Protocol 2021-0695 
charge of the case, and/or that the patient – after his/her procedure – wishes to withdraw from 
the study and exclude his/her information from our analysis.  
 
i Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence 
of kidney stones in the United States. Eur Urol. 2012 Jul;62(1):160-5. 
ii Geraghty RM, Jones P, Somani BK. Worldwide Trends of Urinary Stone Disease Treatment 
Over the Last Two Decades: A Systematic Review. J Endourol 2017 Jun;31(6):547-556. 
iii Assimos D, Krambeck A, Miller NL, et al: Surgical Management of Stones: American Urological 
Association/Endourological Society Guideline, PART II. J. Urol. 2016. 
iv Andreeva V, Vinarov A, Yaroslavsky I, et al. Preclinical comparison of superpulse thulium fiber 
laser and a holmium:YAG laser for lithotripsy. World J Urol. 2020 Feb;38(2):497-503. 
v Ventimiglia E, Doizi S, Kovalenko A, et al. Effect of temporal pulse shape on urinary stone 
phantom retropulsion rate and ablation efficiency using holmium:YAG and super-pulse thulium 
fibre lasers. BJU Int. 2020 Jul;126(1):159-167. 
vi Bagrodia A, Gupta A, Raman JD, et al. Predictors of cost and clinical outcomes of 
percutaneous nephrostolithotomy. J Urol. 2009 Aug;182(2):586-90. 
vii Schuster TG, Hollenbeck BK, Faerber GJ, Wolf JS Jr. Complications of ureteroscopy: analysis of 
predictive factors. J Urol. 2001 Aug;166(2):538-40. 
viii Patel, Nishant, et al. Accuracy of endoscopic intraoperative assessment of urologic stone 
size. Journal of Endourology 28.5 (2014): 582-586. 
ix Whitehurst L, Pietropaolo A, Geraghty R, Kyriakides R, Somani BK. Factors affecting operative 
time during ureteroscopy and stone treatment and its effect on outcomes: retrospective results 
over 6.5 years. Ther Adv Urol 2020;12:1756287220934403. 
x Pearle MS, Goldfarb DS, Assimos DG et al: Medical management of kidney stones: AUA 
Guideline. J Urol 2014; 192: 316. 
xi Kronenberg P, Somani B. Advances in lasers for the treatment of stones: A systematic review. 
Curr Urol Rep 2018;19:45. 
xii Traxer O, Dymov A, Rapoport L, et al. Comprehensive clinical study of super pulse tm fiber 
laser for treatment of stone disease. J Urol. 2019;201(supplement 4).