Better Lithotripsy and Ureteroscopy Evaluation of Stenting (BLUES) A Pragmatic Randomized Multi-center Comparative Effectiveness Study
Phase: NA
Conditions: Renal Stone, Ureteral Stone
Sponsor: University of Michigan

 
 
 
 
 
 
 
Better Lithotripsy and Ureteroscopy Evaluation of Stenting (BLUES):  
A pragmatic randomized multi-center comparative effectiveness study of silicone vs non-silicone stents 
for ureteroscopy in patients with kidney stone disease   
 
NCT05026710 
 
Officially IRB Approved on 12JUNE2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
2 
 
 
 
PROTOCOL NUMBER HUM00199486 
 
 
Better Lithotripsy and Ureteroscopy Evaluation of Stenting (BLUES):  
A pragmatic randomized multi-center comparative effectiveness study of silicone vs non-silicone stents 
for ureteroscopy in patients with kidney stone disease   
 
 
Principal Investigator:  
Khurshid R. Ghani, MD 
 
 
 
 
University of Michigan 
 
 
 
 
Department of Urology 
 
 
 
 
Taubman Center Floor 2 Reception C 
1500 E. Medical Center Drive SPC 5330 
Ann Arbor, MI 48109 
Phone: (734) 936-7030 
Fax: (734) 232-2400 
Email: kghani@med.umich.edu 
 
Sub-Investigator(s): 
 
Russell Becker, MD, PhD 
 
 
 
 
University of Michigan 
 
 
 
 
Department of Urology 
 
 
 
 
Taubman Center Floor 2 Reception C 
1500 E. Medical Center Drive SPC 5330 
Ann Arbor, MI 48109 
Phone: (734)-936-7030 
Fax: (888) 419-2656 
Email: beckerr@med.umich.edu 
 
Biostatistician: 
 
Stephanie Daignault-Newton 
 
 
 
 
University of Michigan 
 
 
 
 
2800 Plymouth Rd, NCRC Building 16 
Ann Arbor, MI 48109 
 
 
 
 
Phone: (734) 615-1396 
Fax: 734-232-2400 
 
 
 
 
Email: sfaruzzi@med.umich.edu 
 
Study Intervention:  Usual urological care of insertion of ureteral stent at the end of ureteroscopy for 
stone disease. Study arms will consist of either Coloplast Imajin Hydro ureteral stent 
vs. non-silicone Polyurethrane/Percuflex ureteral stent (any manufacturer).   
 

HUM00199486 
________________________________________________________________________ 
 
 
3 
Initial version:  
 
8/19/2021  
Amended: 
 
 
05/23/2025 
 

HUM00199486 
________________________________________________________________________ 
 
 
4 
ABBREVIATIONS 
AE 
Adverse Event 
AUA 
American Urological Association 
BCBSM 
Blue Cross Blue Shield of Michigan 
BLUES 
Better Lithotripsy and Ureteroscopy Evaluation of Stenting 
CFR 
Code of Federal Regulations 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DOOR 
Desirability Of Outcome Ranking 
DSMC 
Data Safety Monitoring Committee 
ED 
Emergency Department 
EMA 
Ecological Momentary Assessments 
FDA 
Food and Drug Administration 
HRQoL 
Health Related Quality of Life 
ICH GCP 
International Conference on Harmonisation Good Clinical Practice 
ICIQ-S 
International Consultation on Incontinence Questionnaire - Satisfaction 
ICU 
Intensive Care Unit 
IRB 
Institutional Review Board 
LURN SI-10 
Lower Urinary Tract Dysfunction Research Network Symptom Index 
LUTS 
Lower Urinary Tract Symptoms 
m-ITT 
Modified Intent-to-Treat 
MUSIC 
Michigan Urological Surgery Improvement Collaborative 
NIH 
National Institutes of Health 
PI 
Primary Investigator 
PRO 
Patient Reported Outcome 
PROMIS® 
Patient-Reported Outcomes Measurement Information System 
QI 
Quality Improvement 
RCT 
Randomized Controlled Trial 
ROCKS 
Reducing Operative Complications from Kidney Surgery 
SAE 
Serious Adverse Event 
SoA 
Schedule of Activities 
U-CTO 
Urology Clinical Trials Office 
URS 
Ureteroscopy 
US 
United States 
USSQ 
Ureteral Stent Symptom Questionnaire 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
5 
Section 1: STUDY SCHEMA 
Prior to  
Enrollment 
 
 
Evaluation 1 
 
 
 
 
Evaluation 2 
Operative Day 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Postoperative 
 Days: 1 - 10 
 
  
 
 
 
 
 
 
 
 
 
 
 Postoperative 
 Day: ≤ 30 
 
 
 
 
 
 
Postoperative 
 Day: 28 – 42 
 
 
 
 
 
Postoperative 
 Day: ≤ 60 
 
 
  Screen potential participants by inclusion and exclusion criteria 
Standard urological assessment, obtain history, document discussion with subject 
about study 
Baseline ROCKS PRO questionnaire   
Follow-up assessments of study endpoints and safety 
ED visits, hospitalizations, ambulatory care, patient/caregiver time off work 
 (Schedule of Activities) 
Daily Ecological Momentary Assessments: Post-operative days 1-10 
Day 7 ROCKS PRO questionnaire 
(Schedule of Activities) 
Final Assessments 
Refer to (Schedule of Activities) 
Arm 2 
112 
Arm 1 
112 
Randomize 
Follow-up assessments of study endpoints and safety 
Week 4 ROCKS PRO questionnaire 
(Schedule of Activities) 
Follow-up assessments of study endpoints and safety 
Renal imaging 
(Schedule of Activities) 
224: Confirm inclusion and exclusion criteria 
Obtain informed consent. 

HUM00199486 
________________________________________________________________________ 
 
 
6 
Section 2: STUDY SYNOPSIS 
Title: 
Better Lithotripsy and Ureteroscopy Evaluation of Stenting (BLUES) in 
Michigan Urological Surgery Improvement Collaborative (MUSIC) 
Study Description: 
Multi-center pragmatic randomized comparative effectiveness study of 
ureteral stent composition for ureteroscopy in patients with kidney stone 
disease. We hypothesize that a ureteral stent made of silicone, will have 
superior outcomes when compared to non-silicone stents.  
Objectives: 
Primary objective:  
• 
To assess health-related quality of life in patients with urinary stone 
disease stented with silicone or non-silicone ureteral stents at 
ureteroscopy  
 
Secondary objectives:  
• 
To compare 30-day emergency department visits and hospitalization 
rates between study arms 
• 
To compare rates and intensity of ambulatory healthcare encounters 
after ureteroscopy and stenting between study arms 
• 
To compare stone-free rates between study arms 
• 
To compare abnormal imaging findings after ureteroscopy and stenting 
between study arms 
Endpoints: 
Primary Endpoint:  
• 
PROMIS® scores of pain intensity and pain interference at 7 days  
Secondary Endpoints:  
• 
PROMIS® scores of pain intensity and interference at 4 weeks 
• 
NIH LURN SI-10 scores at 7 days 
• 
NIH LURN SI-10 scores at 4 weeks 
• 
Composite healthcare utilization metric within 30 days  
o 
Hospitalization and ICU care 
o 
Unplanned hospitalization 
o 
Emergency department visit 
o 
Ambulatory encounter: Clinic visit 
o 
Ambulatory encounter: Phone call or message 
• 
Abnormal imaging findings within 60 days 
• 
Stone-free rates within 60 days 
Exploratory Endpoints: 
• 
Number of days taken off work by patient 
• 
Number of days taken off work by caregiver 
• 
Ecological Momentary Assessments (EMA) measured via daily text 
message for 10 days 
o 
Daily visual analog scale pain survey score  
o 
PROMIS® daily ability to participate in social roles and 
activities score 
• 
Composite score difference between Winratio and Desirability Of 
Outcome Ranking (DOOR)  
• 
Number of patients receiving opioid prescriptions  
• 
ICIQ-S Treatment Satisfaction scores at 7 days 
• 
ICIQ-S Treatment Satisfaction scores at 4 weeks 
Study Population: 
224 patients, any gender, age ≥18 years, in the State of Michigan 
Phase: 
Not applicable 
Description of 
Sites/Facilities 
Enrolling Participants: 
Multi-center study of 6 urology practices within the Michigan Urological 
Surgery Improvement Collaborative (MUSIC) with University of Michigan as 
the coordinating center.  
Description of Study 
Intervention: 
Insertion of ureteral stent at the end of ureteroscopy for stone disease. 
Study arms will consist of either silicone (Coloplast Imajin Hydro) ureteral 

HUM00199486 
________________________________________________________________________ 
 
 
7 
stent vs. non-silicone (Polyurethrane/Percuflex) ureteral stent (any 
manufacturer).   
Study Duration: 
30 months (3 months pre-enrollment and set up; 24 months patient 
enrollment; 3 months study close and analysis). 
Participant Duration: 
2 months 
 
 
 
Section 3: STATEMENT OF COMPLIANCE 
The study will be carried out in accordance with United States (US) Code of Federal Regulations (CFR) 
applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or 21 CFR Part 812)  
 
The funded investigators and clinical trial site staff who are responsible for the conduct, management, or 
oversight have completed Human Subjects Protection Training. 
 
The protocol, informed consent form(s), and all participant materials will be submitted to the Institutional 
Review Board (IRB) for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. In addition, all changes to the 
consent form will be IRB-approved; a determination will be made regarding whether a new consent needs 
to be obtained from participants who provided consent, using a previously approved consent form. 
 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
8 
THIS PAGE IS INTENTIONALLY LEFT BLANK 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
9 
Section 4: STUDY BACKGROUND AND RATIONALE  
 
Section 4.1: Study Environment 
The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a physician-led quality 
collaborative comprised of a consortium of urology practices. The collaborative is designed to evaluate 
and improve the quality and cost-efficiency of urological care in the state of Michigan. The collective 
benefits of this effort will extend to providers, healthcare systems, and most importantly, patients with 
urologic conditions including prostate cancer, kidney stones and small renal mass diagnoses. The MUSIC 
vision is to be an innovator in physician-led quality improvement (QI) activities related to the care for 
patients with urologic diseases. By collecting clinically-relevant data, comparing performance among 
peers, sharing best practices, and implementing changes in clinical behavior we will achieve more 
efficient utilization of healthcare resources, improve care delivery in our own environments, and enhance 
the quality, value, and treatment outcomes for men and women in Michigan with various urologic 
diseases. Part of MUSIC, the Reducing Operative Complications from Kidney Stones (ROCKS) initiative 
aims to improve the quality of care specifically for patients with kidney stones.  One of the primary 
objectives of ROCKS is to reduce modifiable Emergency Department (ED) visits following commonly 
performed kidney stone surgeries such as ureteroscopy and shockwave lithotripsy. Started in 2016, 
ROCKS has made significant efforts to improve multiple aspects of the surgical journey for patients with 
kidney stones.   
 
ROCKS PRO is a QI initiative that allows urologists in Michigan to better understand the patient 
experience following kidney stone surgery. This allows development of enhanced recovery pathways for 
patients undergoing kidney stone surgery with the hope to improve overall patient care across the state. 
 
ROCKS PRO utilizes questions from several validated PRO questionnaires. These include the Patient-
Reported Outcomes Measurement Information System (PROMIS®), a validated instrument developed by 
the National Institutes of Health to assess pain and bother in patients. It consists of questions regarding 
the patients’ health-related symptoms of function and pain management (pain intensity and interference). 
ROCKS PRO also utilizes questions from the Lower Urinary Tract Dysfunction Research Network 
(LURN)-Symptom Index (LURN SI-10) questionnaire, the International Consultation on Incontinence 
Questionnaire (ICIQ)-Satisfaction (ICIQ-S), two questions regarding time off work for themselves and their 
caregiver, and one additional question asked to address ureteral stent specific regret taken from the 
Ureteral Stent Symptom Questionnaire. The LURN SI-10 assesses urinary frequency, nocturia, urgency, 
incontinence, bladder pain and voiding. ICIQ-S is a validated questionnaire that assesses aspects of 
experience, expectations, and outcomes to evaluate satisfaction after surgery. (Figure 1) 
 
The aims of ROCKS PRO are as follows: 
• 
Improve patient outcomes following ureteroscopy and shockwave lithotripsy through data 
collection, performance feedback, and sharing of best practices. 
• 
Develop ways to improve post-operative outcomes through the collection and analysis of PRO 
surveys for MUSIC patients by tracking their recovery after undergoing kidney stone surgery.  
 
Section 4.2: Epidemiology 
Nephrolithiasis (kidney stone disease) affects 1 in 10 people in the United States.(1) 10.9% of patients 
with nephrolithiasis undergo ureteroscopy (URS) for treatment.(1) URS, is a relatively quick procedure, 
performed mainly at ambulatory centers, where a semi-rigid or flexible endoscope is inserted into the 
ureter or kidney via the urethra to treat urinary stones. Recent data demonstrates that URS is the most 
common surgical therapy for nephrolithiasis,(2, 3) and it is estimated that over 500,000 procedures are 
performed annually in this country.(4) Following URS for nephrolithiasis, ureteral stents are commonly 
placed for a temporary period of time permitting drainage of urine from the kidney. In the state of 
Michigan, 73% of urologists place a ureteral stent after URS with surgeon variation ranging from 10 to 
100%.(5) While routinely used, ureteral stents are associated with patient morbidity that includes pain, 
urinary discomfort, unplanned ED visits, and hospitalization.(5) Prior work has demonstrated that stent 
morbidity can result in patient suffering, lost economic revenue due to work incapacity, and an increase in 
healthcare costs due to unplanned healthcare utilization.(6) Patients with ureteral stents after URS have 
been shown to consume significant healthcare recourses especially in the ambulatory care environment, 

HUM00199486 
________________________________________________________________________ 
 
 
10
where nurses and doctors have to deal with enquiries of patient pain, prescribing medication, and 
unplanned office visits.(7) 
 
Section 4.3: Current Practice 
A ureteral stent is a flexible, small, hollow tube measuring 24-30 cm in length that sits between the 
bladder and kidney, and permits drainage of urine from the kidney. Ureteral stents are FDA approved 
devices and widely available as guideline recommended care for ureteroscopy. Stents are designed and 
utilized to avoid adverse events and unplanned operations after URS such as for urinary obstruction or 
sepsis.(8) Stent placement is recommended after URS in many clinical scenarios for a temporary period 
of time permitting drainage of urine from the kidney. There are specific indications for stent use, and not 
all patients require it. American Urological Association (AUA) guidelines recommend stent placement for 
patients undergoing ureteroscopy with ureteric injury, evidence of ureteral obstruction, a large stone 
burden (>1.5 cm), a solitary kidney, renal functional impairment, and in those in whom another ipsilateral 
procedure is planned.(8) Urologists report placing ureteral stents routinely in approximately 80% of all 
cases.(9) The risks of stents include: infection, encrustation, obstruction, rupture, migration, bladder 
irritation symptoms, pain, hematuria, erosion. Following placement, the stent is often removed 1-3 weeks 
later by the urologist in the office.  
 
In MUSIC, we recently performed an extensive RAND/UCLA Appropriateness Method process involving 
15 diverse urologists across Michigan to define uncomplicated URS in real-world practice and provide 
information on clinical scenarios appropriate for stent omission (Appendix 1). During this process it was 
clear that very few urologists would consider stent omission for larger stones (i.e. stones 1-1.5 cm in size) 
regardless of its location (renal or ureteral) (dark red bars in Appendix 1), or even for smaller stones, if a 
device during surgery called the ureteral access sheath (UAS), was used (light red bars in Appendix 1). 
The UAS is used in 37% of URS cases in Michigan.(10) We also learned from this process that many 
urologists would opt for stent omission if the patient was pre-stented, i.e. having a stent already in place 
at the time of surgery because it was placed as an emergency in patients with ureteral colic and 
obstruction. This process in MUSIC has provided us real-world information that allowed us to design a 
clinical study with appropriate inclusion criteria that can optimally assess the benefits of ureteral stenting 
in clinical practice. 
 
Section 4.4: Justification 
Stents themselves are associated with significant patient morbidity that includes pain, blood in the urine, 
lower urinary tract symptoms (LUTS) and urinary discomfort which can result in an ED visit for evaluation, 
and sometimes hospitalization because of infection.(5) There has been great interest in the role of 
silicone as an alternative stent material due to the potential for decreased patient morbidity and 
encrustation.(11, 12) Bacterial biofilm formation and mineral deposition (encrustation) lead to ureteral wall 
inflammation, trauma and pain. Prospective clinical studies comparing the use and outcomes of non-
silicone stents versus silicone stents is limited, but has demonstrated improvements in stent related 
morbidity and pain.(12, 13) To date, there have been no studies examining outcomes of silicone ureteral 
stent placement in the US healthcare system using validated and patient friendly PRO measures, that 
also assess the downstream consequences of healthcare resources including ambulatory 
nursing/physician care utilization and unplanned healthcare encounters such as ED visits. Therefore, we 
propose a comparative effectiveness study to assess outcomes of a standard non-silicone ureteral stent 
versus silicone ureteral stent placement after URS to understand differences in patient health-related 
quality of life, morbidity, and its consequences for patients and their caregivers. The pragmatic study 
design will encourage patient and urologist participation and reduce resource use. Our proposed study 
will be the first to evaluate the Imajin silicone stent in the United States healthcare system. MUSIC has 
become an international leader in urological quality improvement and is uniquely situated to provide 
practical real-world evidence that has the potential to change practice. 
 
No more than minimal increased risk to the participants is expected for the present study. All potential 
participants are planning to undergo a surgical procedure (URS) with a board-certified urologist trained in 
URS with stent placement in accordance with AUA guidelines. They will be placing either a non-silicone 
(standard) ureteral stent or a silicone ureteral stent, both of which are FDA approved.(14, 15) Neither the 
stent, study protocol, nor manual of operation requires alteration to standard of care. 

HUM00199486 
________________________________________________________________________ 
 
 
11
 
Section 4.5: Potential Benefits 
Immediate. Based upon prior RCT outside of the United States, the use of silicone ureteral stents has the 
potential to decrease pain and LUTS after URS.(12) Decreased pain and LUTS after URS secondarily 
could decrease the rate of ambulatory healthcare utilization, opioid prescriptions, postoperative ED visits, 
and unplanned hospitalizations. It could also decrease the number of days required to miss work due to 
recovery. 
 
Long-range. Decreased pain and LUTS after URS secondarily could decrease a patient’s exposure to 
opioid analgesia postoperatively. Less patient requirements for opioid analgesia could decrease the 
incidence of new persistent long-term use of opiates in these patients. 
 
 
Section 5: STUDY OBJECTIVES 
Section 5.1: Primary Objectives 
1. 
To determine the health-related quality of life and symptoms in patients with urinary stone 
disease stented with silicone or polyurethane stents at ureteroscopy.  
 
Section 5.2: Secondary Objectives  
1.  
To compare 30-day emergency department visits and hospitalization rates between study arms 
 
2.  
To compare rates and intensity of ambulatory healthcare encounters after ureteroscopy and 
stenting between study arms 
 
3.  
To compare stone-free rates between study arms 
 
4.  
To compare abnormal imaging findings after ureteroscopy and stenting between study arms 
 
Section 5.3: Exploratory Objectives 
 
1.  
To compare days taken off work by patient between study arms 
 
2.  
To compare days taken off work by caregiver between study arms 
 
3.  
To compare Ecological Momentary Assessments (EMA) measured via daily text message for 
10 days between study arms 
 
4.  
To compare Composite score difference between Winratio and Desirability Of Outcome 
Ranking (DOOR) between study arms 
 
5.  
To compare number of patients receiving opioid prescriptions between study arms 
 
6.  
To compare ICIQ-s score at 7 days between study arms 
 
7.  
To compare ICIQ-s score at 4 weeks between study arms 
 
Section 5.4: Endpoints 
• 
Primary Efficacy Endpoint(s):  
o 
Silicone stent placement will be associated with significantly improved PROMIS® scores 
of pain intensity and interference at 7 days compared to non-silicone stent placement. 
 
• 
Secondary Efficacy Endpoint(s): 
o 
Silicone stent placement will be associated with equivalent PROMIS® scores of pain 
intensity and interference at 4 weeks compared to non-silicone stent placement. 
o 
Silicone stent placement will be associated with significantly improved NIH LURN SI-10 
scores from baseline at 7 days compared to non-silicone stent placement. 

HUM00199486 
________________________________________________________________________ 
 
 
12
o 
Silicone stent placement will be associated with equivalent difference in NIH LURN SI-10 
scores from baseline at 4 weeks compared to non-silicone stent placement. 
o 
Silicone stent placement will be associated with improved composite healthcare 
utilization metric within 30 days compared to non-silicone stent placement. 
 
Hospitalization and ICU care 
 
Unplanned hospitalization 
 
Emergency department visit 
 
Ambulatory encounter: Clinic visit 
 
Ambulatory encounter: Phone call or EMR message 
o 
Silicone stent placement will be associated with equivalent abnormal imaging findings 
within 60 days compared to non-silicone stent placement. 
 
New/worsening hydronephrosis 
o 
Silicone stent placement will be associated with equivalent stone-free rates within 60 
days compared to non-silicone stent placement.  
 
• 
Tertiary/Exploratory Endpoints(s): 
o 
Silicone stent placement will be associated with significantly improved Ecological 
Momentary Assessment (EMA) scores measured via daily text message for 10 days 
compared to non-silicone stent placement. 
 
Daily visual analog scale survey for pain 
 
PROMIS® daily ability to participate in social roles and activities score 
o 
Silicone stent placement will be associated with significantly less number of days taken 
off work by patient. 
o 
Silicone stent placement will be associated with significantly less number of days taken 
off work by caregiver.  
o 
Silicone stent placement will be associated with significantly improved composite 
healthcare utilization metric within 30 days compared to non-silicone stent placement 
using Desirability of Outcome Rating (DOOR) method 
 
The WinRatio and DOOR composite healthcare utilization metric ratios' sizes and 
directions will be compared. 
o 
Silicone stent placement will be associated with significantly less number of opioid 
prescriptions received. 
o 
Silicone stent placement will be associated with significantly improved ICIQ-S scores at 7 
days compared to non-silicone stent placement. 
o 
Silicone stent placement will be associated with significantly improved ICIQ-S scores at 4 
weeks compared to non-silicone stent placement. 
 
 
Section 6: PATIENT ELIGIBILITY 
The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a Michigan-based, physician-
lead quality collaborative comprised of a consortium of urology practices. The collaborative is designed to 
evaluate and significantly improve the quality and cost efficiency of urologic care in the state of Michigan. 
The participating sites submit data to the MUSIC clinical registry maintained by the MUSIC Coordinating 
Center and attend tri-annual consortium-wide meetings each year to compare performance, share best 
practices, and ultimately implement changes in clinical behavior. The consortium is funded by Blue Cross 
Blue Shield of Michigan (BCBSM) and the program activities are managed by the MUSIC Coordinating 
Center, which is housed at the University of Michigan. 
 
ROCKS is a QI initiative within MUSIC to measure the frequency of ED visits following ureteroscopy.   
 
Eligible BLUES patients include those that are enrolled in MUSIC ROCKS and ROCKS PRO and >18 
years of age with a kidney or ureteral stone and are planned to have a ureteroscopy where stent 
placement is planned. Based on inclusion and exclusion criteria these patients will be identified in the 
clinic by MUSIC urologists at practices participating in BLUES.  
 

HUM00199486 
________________________________________________________________________ 
 
 
13
Subjects must meet all of the inclusion and exclusion criteria to be enrolled to the study. Study treatment 
may not begin until a subject is enrolled. 
 
Section 6.1: Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the study  
3. Male or female, aged ≥18 years  
4. Planned treatment of unilateral renal and/or ureteral stones, largest stone ≤ 2.0 cm in size measured 
on abdominal x-ray, Ultrasound or CT scan. 
i. Renal stone defined as only renal location of stone(s). 
ii. Ureteral stone defined as ureteral only or ureteral and renal stone(s). 
5. Planned unilateral ureteroscopy with stent placement without stent string. 
6. Ability to take oral medication.  
7. Ability and willingness to complete and adhere to survey questions and responses throughout study 
duration. 
 
Section 6.2: Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Known planned secondary or staged procedure  
2. Presence of anatomical anomalies (e.g. solitary, horseshoe, fused crossed ectopia, pelvic kidney) 
3. Presence of any prior urinary diversion (e.g. ileal conduit, orthotopic neobladder) 
4. Presence of any indwelling ureteral stent prior to ureteroscopy 
5. Presence of any indwelling nephrostomy tube prior to ureteroscopy  
6. Ancillary ureteroscopy to treat residual fragments in the 3 months after percutaneous renal stone 
surgery.  
7. Renal stone located in diverticulum 
8. No indication for stent placement (e.g. spontaneous passage) 
9. Bladder stone location 
10. Pregnancy or lactation 
11. Known allergic reactions to polyurethane or silicone 
 
 
Section 7: SUBJECT SCREENING AND REGISTRATION PROCEDURES 
Subjects will be recruited from predesignated MUSIC Urology clinics at participating institutions/sites.  
 
Participating MUSIC Urologists will evaluate patients in their clinical practice for study inclusion or 
exclusion criteria. Preoperative evaluation, labs and imaging studies will be evaluated per the standard 
practice of the participating urologist based off best practice recommendations. It is the responsibility of 
the local site investigator/delegate to determine patient eligibility. If the urologist identifies their patient 
as a potential participant, the study will be discussed with them at their evaluation. The BLUES study 
brochure may also be given to the potential participant. If the subject expresses an interest, the 
urologist or local site delegate will contact the BLUES study team with the patient contact information 
and stone location (renal only or ureteral). The BLUES study team consists of the MUSIC ROCKS 
program manager, statistician, BLUES study coordinator(s), study principal investigator, and study co-
investigator. 
 
Enrollment in BLUES is voluntary. If a patient does agree to participate in BLUES, they will be enrolled 
prior to undergoing ureteroscopy and stent placement. The patient will undergo surgical consent for 
ureteroscopy and stenting per the routine clinical care process. Patients who agree to take part in the 
BLUES study will have their name, contact, and other clinical information relevant to their upcoming 
ureteroscopy and stent placement entered into the MUSIC registry.  
 
Prospective study participants may be consented by the BLUES study coordinator, other BLUES study 
team member, the site principal investigators, or other site employees trained and approved to conduct 
study related activities per local IRB policies. The individual performing the consenting process will 

HUM00199486 
________________________________________________________________________ 
 
 
14
educate the patient on the study and protocol by phone, video communication, or in person. If the 
potential participant continues to express interest in participation, study materials and consent will be 
provided to the patient via an E-consenting platform compliant with 21 CFR 11, such as SignNow or 
REDCap. Paper consent forms using handwritten signatures may also be used in lieu of E-consenting. 
Consent forms will be IRB-approved and the participant will be asked to read and review the document. 
The individual conducting the consenting will explain the research study to the participant and answer any 
questions that may arise. A verbal explanation will be provided in terms suited to the participant’s 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants. Participants will have the opportunity to carefully review the written consent form 
and ask questions prior to signing. The participants will have the opportunity to discuss the study with 
their family or surrogates or think about it prior to agreeing to participate.  
 
The participant will sign the informed consent document prior to any procedures being done specifically 
for the study. The ROCKS PRO baseline questionnaire is being completed as a part of ROCKS PRO 
program prior to consent being obtained for the BLUES trial. The data received from the ROCKS PRO 
baseline questionnaire will not be part of this research prior to signing BLUES consent. The standard 
urological assessment is not a component of this research, rather, it is conducted simply as a part of a 
urologists clinical practice ahead of a procedure. Participants must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A copy of the 
informed consent document will be given to the participants for their records. The informed consent 
process will be conducted and documented in the source document (including the date), and the form 
signed, before the participant undergoes any study-specific procedures. The rights and welfare of the 
participants will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
 
The BLUES study coordinator, another member of the BLUES study team, or a local site designee will 
register the patient with Arbormetrix for the ROCKS BLUES clinical registry and ROCKS PRO. As part of 
the subject enrollment process, data collection will include all MUSIC, MUSIC ROCKS and ROCKS PRO 
data. If a local performance site designee performs the registration, a member of the BLUES study team 
will review the submitted registration information for accuracy. In addition, a copy of the completed 
Eligibility Worksheet signed and dated by the site investigator or designee will be sent back to the BLUES 
study coordinator. 
 
The individual performing the consenting and/or members of the BLUES study team will be available for 
any further counseling the patient requires to ensure that all questions are answered and to ensure that 
the patient is interested in participation.  
 
Participants at a given performance site who meet all inclusion/exclusion criteria will be randomized using 
Randomize.net or a similar randomization methodology as endorsed by the Michigan Institute for Clinical 
& Health Research (MICHR). Subjects will be randomized to either silicone or non-silicone ureteral stent 
placement at a 1:1 allocation ratio. Blocked, stratified randomization based upon surgeon classified stone 
location (renal only versus ureteral), with random block sizes will be used to ensure group 
balance.  Randomization list will be determined separately in strata defined by state the stratification 
factor/s here. The randomization code will be generated by an independent statistician. 
 
At the time of surgery, if baseline PRO has been completed, prior to placement of the stent, the surgeon 
will be notified via email/text message and the surgeons operating room staff can reference the MUSIC 
registry to confirm if the patient should have a silicone vs non-silicone stent based on random allocation 
by the BLUES study coordinator or another member of the BLUES study team. Only patients who are 
randomized, remain eligible prior to stent placement, and receive the study treatment will be counted 
towards the treatment population of 224 participants. These patients will receive PRO questionnaires, via 
the ROCKS PRO infrastructure, pre-operatively and at 7 days, and 4 weeks after surgery. If the patient is 
unable to complete the PRO questionnaires through the ROCKS PRO infrastructure, the patient may 
complete an email survey via REDCap, survey by phone from a BLUES study team member, or paper 
questionnaires. Patients will also receive text messages which include pain-specific questionnaires to be 
completed daily for 10 days after surgery. The process of completing the ROCKS PRO questionnaire is 

HUM00199486 
________________________________________________________________________ 
 
 
15
the same, regardless of the patient’s participation in the BLUES study. A patient can withdraw or decline 
participation in BLUES and/or ROCKS PRO at any time. 
 
 
Section 8: TREATMENT PLAN 
Section 8.1: Treatment overview  
Participating BLUES practices will utilize the MUSIC Registry and ROCKS PRO as a tool to enroll and 
collect patient surveys. Through ROCKS PRO, patients are provided via email a secure and unique link to 
the MUSIC Registry patient portal. An electronic introduction for ROCKS PRO will then be presented. 
Patients will not be required to participate and may choose to be removed from future correspondence by 
emailing or calling the MUSIC Coordinating Center directly.  
 
If participating, they will be directed to the baseline questionnaire consisting of questions regarding 
health-related symptoms, functions and pain management before undergoing ureteroscopy. Automated 
email survey links will be sent to patients to complete ROCKS PRO questionnaires pre-operatively and at 
7 days, and 4 weeks after surgery (Figure 1). Patients with cell phone numbers who agree to participate 
in BLUES will be asked to complete EMA of pain via a visual analog scale score and one question from 
the PROMIS® Ability to Participate in Social Roles and Activities Questionnaire (Figure 2), for 10 days 
after surgery.  
 
If a patient does not log-in or fails to complete the baseline survey, they will receive an electronic 
automated reminder and will be contacted by the MUSIC Coordinating Center. If a patient does not log-in 
or fails to complete the 7-day survey, they will receive an electronic automated reminder and will be 
contacted by the MUSIC Coordinating Center on day 8 and 9, to facilitate its completion by the end of 
post-operative day 10. The BLUES Study Team may also administer the PRO questionnaires via 
REDCap, phone, or paper if the participant is unable to complete suveys through the MUSIC Registry. 
 
Figure 3 depicts the timeline and flow chart of the recruitment and follow-up process. If it is past the 
patient’s operative date they will not be enrolled or contacted. 
 
The patient’s surgery will proceed per standard of care, and their follow up, imaging and clinic visits will 
be directed by the local surgeon according to their local protocol. The BLUES study is pragmatic. Stents 
will be removed at a time and duration per the surgeon’s discretion. The patient’s information regarding 
post-operative course will be collected into the registry 60 days after the surgery, keeping with current 
practice for MUSIC ROCKS patient registry entry.  
 
Section 8.2: Operative 
It is not anticipated that either arm will be associated with adverse events above and beyond what is 
experienced normally with these therapies. No more than minimal increased risk to the participants is 
expected for the present study. All potential participants are planning to undergo a surgical procedure 
(URS) with a board-certified urologist trained in URS with stent placement in accordance with AUA 
guidelines. They will be placing either a non-silicone (standard) ureteral stent or a silicone ureteral stent, 
both of which are FDA approved. All of which is considered usual care. 
 
At the end of ureteroscopic procedure, a ureteral stent will be placed by the urologist in the standard 
fashion that each urologist is trained to perform. Stent sizing, technique, duration and removal technique 
will be determined by the individual urologist and their standard practice. 
 
Patients randomized to the silicone stent cohort will utilize the Coloplast Imajin Hydro (Silicone Hydro-
Coated Double Loop Ureteral Stent) 
• 
This stent is commercially available and is being used in accordance with approved labeling: “The 
Silicone Hydro-Coated Double Loop Ureteral Stents are used for: 
o 
Drainage of the upper urinary tract over fistulas or ureteral obstacles 
o 
Healing of the ureter” 
• 
Stent sizes  
o 
6fr x 24 

HUM00199486 
________________________________________________________________________ 
 
 
16
o 
6fr x 26 
o 
6fr x 28 
 
Patients randomized to the non-silicone stent cohort will utilize any commercially available non-silicone 
ureteral stent for its approved indication. The stents denoted below are commonly used non-silicone 
stents and are not individually compared against the object of the study (Imajin Hydro silicone stent 
above). 
• 
Device model(s) 
o 
Boston Scientific  
 
Percuflex™ 
 
HYDROGEL COATED Percuflex Plus™ 
 
Contour™ 
o 
Becton Dickinson (Bard) 
 
Bard double pigtail soft polyurethane  
o 
Cook 
 
Sof-Flex double loop polyurethane 
• 
Stent size(s)  
o 
6fr x 24 
o 
6fr x 26 
o 
6fr x 28 
 
Specific assessments obtained on the operative day, include:  
• 
Ureteral stent characteristics 
o 
The ureteral stents in the comparative effectiveness study are FDA approved 
commercially available devices that will be utilized by the urologists. Urologists will be 
trained and educated on documenting the specific size, brand and name of the ureteral 
stent used in the operative report. This data will be collected through the ROCKS clinical 
registry. 
 
Section 8.3: Post-Operative 
The patient’s post-operative care will proceed per standard of care, and their follow up, imaging and clinic 
visits will be directed by the local surgeon according to their local protocol. All patients will be provided 
with the MUSIC pain optimization pathway (POP) medication for post-operative symptoms for 
ureteroscopy. The standard within MUSIC is to prescribe non-steroidal anti-inflammatory drugs (NSAIDs), 
alpha-blockers and an anti-cholinergic as first line therapy. Opiate pain medication is not recommended 
as first line therapy. Patients will also be provided the MUSIC pain management and stent specific 
education brochures.  
 
The BLUES study is pragmatic. Stents will be removed at a time and duration per the surgeon’s 
discretion. The patient’s information regarding post-operative course will be collected into the registry 60 
days after the surgery, keeping with current practice for MUSIC ROCKS patient registry entry.  
 
Specific assessments obtained on the postoperative day 1 through 10, include: 
• 
ROCKS PRO day 7 questionnaire 
o 
Participants will complete their day 7 ROCKS PRO questionnaire, consisting of 
PROMIS® scores of pain intensity and interference, LURN SI-10 score Baseline ICIQ-S 
score, stent specific USSQ question and reported number of days off work (Figure 1) 
• 
Ecological Momentary Assessment (EMA) measured via daily text message 
o 
Participants will complete a single visual analog scale survey for pain and one functional 
ability question from the PROMIS® ability to participate in social roles and activities 
(Figure 2) 
 
Specific assessments obtained on the postoperative day ≤ 60, include: 
• 
ROCKS PRO 4-week questionnaire 

HUM00199486 
________________________________________________________________________ 
 
 
17
o 
Participants will complete their 4-week postoperative ROCKS PRO questionnaire, 
consisting of PROMIS® scores of pain intensity and interference, LURN SI-10 score 
Baseline ICIQ-S score, stent specific USSQ question (Figure 1) 
• 
Stone-free rates within 60 days 
o 
Participants after URS are often requested to obtain renal imaging within 8 weeks. 
However, since this is a pragmatic study, patients are asked to receive imaging based on 
provider discretion, and some patients do not attend their imaging appointment, Utilizing 
MUSIC and ROCKS existing infrastructure. Stone free defined as no residual fragments 
identified on any postoperative imaging (ultrasound, abdominal X-ray, CT or any 
combination) within 60 days  
 
Section 8.4: Concomitant Medications/Treatments 
During this study, participants are asked to adhere to the recommendations of their treating surgeon. 
The use of the MUSIC ROCKS physician pain medication guidance and patient specific educational 
resources for ureteroscopy and stenting is recommended.  
 
Section 8.5: Other Modalities or Procedures 
Not applicable. 
 
Section 8.6: Duration of Therapy 
At the end of ureteroscopic procedure, a ureteral stent will be placed by the urologist in the standard 
fashion that each urologist is trained to perform. Stent sizing, technique, duration and removal technique 
will be determined by the individual urologist and their standard practice. 
 
Patient study period will not exceed 60 days postoperatively unless related to a serious adverse event 
(SAE).  
 
Section 8.7: Off Treatment Criteria  
A participant is considered to have completed the study if he or she has completed all phases of the study 
including the last visit or the last scheduled procedure shown in the SoA, and is >60 days after their 
procedure. 
 
Section 8.8: Duration of Follow-Up 
60 days postoperatively unless related to a serious adverse event (SAE).  
 
Section 8.9: Off Study Criteria 
Discontinuation from the BLUES study does not mean discontinuation from the study. No temporary 
discontinuations will be allowed due to short term patient participation. The pragmatic nature of the study 
enables continued standard of care postoperative care as directed by their treating urologist. Patients will 
have been enrolled into MUSIC ROCKS and ROCKS PRO. Study procedures as indicated by the study 
protocol will be tracked and recorded. If a clinically significant finding is identified (including, but not 
limited to changes from baseline) after enrollment, the investigator or qualified designee will determine if 
any change in participant management is needed. Any new clinically relevant finding will be reported if 
necessary as defined in section 10. 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
 
• 
Participant, treating urologist and/or local PI will contact the local study team member or the 
BLUES study team directly with the following: 
o 
Specific underlying reason for discontinuation   
 
The local site study team member will notify the BLUES study team to ensure the participant 
discontinuation status is recorded if the BLUES study team was not contacted directly. 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 

HUM00199486 
________________________________________________________________________ 
 
 
18
• 
Significant study SoA non-compliance  
o 
No phone call, text message or email responses per SOA or study coordinator inquiries 
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant unable to receive phone calls, text messages or email for 5 of the 10 days 
postoperatively. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Case 
Report Form (CRF) by the local study team member. Subjects who sign the informed consent form and 
are randomized but do not receive the study intervention may be replaced.  Subjects who sign the 
informed consent form, and are randomized and receive the study intervention, and subsequently 
withdraw, or are withdrawn or discontinued from the study, will not be replaced. 
 
Section 8.10: Patient Replacement 
Subjects who sign the informed consent form, and are randomized and receive the study intervention, 
and subsequently withdraw, or are withdrawn or discontinued from the study, will not be replaced. 
 
Subjects who are found to be ineligible at any time prior to ureteral stent placement may be replaced. 
 
Section 9: STUDY PROCEDURES 
Time and Events Table 
Procedures 
Baseline Evaluation 
Prior to operation 
Operative Day 
Ambulatory Assessments  
Days 1-10 
Ambulatory Assessment 
Day 7 2 
Postoperative visit: Stent 
removal 
Ambulatory Assessment 
Week 4 3 
Day ≤ 30 
Day ≤ 60 
Informed consent 
 
X 
 
 
 
 
 
 
 
Study education 
 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
Study intervention 
 
 
 
X 
 
 
 
 
 
Radiologic imaging assessment 1 
X 
 
 
 
 
 
 
 
 
Daily EMA 
 
 
 
X 
 
 
 
 
 
ROCKS PRO 
 
X 
 
 
X 
 
X 
 
 
Follow-up assessments of study 
endpoints and safety 
 
 
 
 
 
 
 
X 
X 
Complete Case Report Form (CRF) 
 
 
X 
 
 
X 
 
X 
X 
 
1: Urological imaging modality performed nearest to but prior to operative date. 
 
2: Day 7 ambulatory assessment can be completed from post-operative day 7 through day 10. 
 
3: Week 4 ambulatory assessment can be completed from post-operative day 22 through day 42. 
 
 
Section 10: ADVERSE EVENTS 

HUM00199486 
________________________________________________________________________ 
 
 
19
Section 10.1: Adverse Event Reporting Requirements 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial and is done to ensure 
the safety of subjects enrolled in the studies as well as those who will enroll in future studies using similar 
agents. Data on adverse events will be collected from the time of the initial study intervention through 30 
days after the study intervention. Any serious adverse event that occurs more than 30 days, and before 
60 days of the study intervention and is considered related to the study intervention must also be 
reported. Serious Adverse Events (SAEs) will continue to be followed until: 
• 
Resolution or the symptoms or signs that constitute the serious adverse event return to baseline; 
• 
There is a satisfactory explanation other than the study intervention for the changes observed; or  
• 
Death. 
 
The investigator is responsible for the detection, documentation, grading, and assignment of attribution 
and expectedness of events meeting the criteria and definition of an AE or SAE. The definitions of AEs 
and SAEs are given below. It is the responsibility of the principal investigator to ensure that all staff 
involved in the trial is familiar with the content of this section. 
 
Any medical condition or laboratory abnormality with an onset date before the initial study intervention will 
be considered pre-existing in nature. Any known pre-existing conditions that are ongoing at the time of 
study entry should be considered medical history. 
 
For this study, non-serious AEs will not be reported to the IRB. SAEs will be reported in keeping with the 
governing IRBs guidelines. 
 
Section 10.2: Definitions 
 
1. Adverse Event 
For the purposes of this trial, an adverse event (AE) is considered any untoward medical occurrence in a 
patient receiving study treatment that has or potentially has a causal relationship with this treatment. Any 
untoward medical occurrences that are unrelated to the study intervention will not be considered adverse 
events. 
 
Symptoms of kidney stone disease and expected side effects from ureteroscopy lithotripsy and stent 
placement are not considered adverse events for this study. The following symptoms are indicative of 
underlying kidney stone disease and expected side effects from ureteroscopy with laser lithotripsy and 
stent placement, and will not be reported as adverse events (unless the event meets the criteria of an 
SAE): 
• 
Hematuria 
• 
Irritative voiding symptoms (e.g., urinary frequency, urgency, dysuria) 
• 
Abdominal/flank/bladder pain 
• 
Nausea and/or vomiting 
• 
Dizziness and lightheadedness  
• 
Urinary retention 
 
Abnormal laboratory values or test results constitute adverse events only if they induce clinical signs or 
symptoms or require therapy. They are to be captured under the signs, symptoms, or diagnoses 
associated with them. 
 
2. Serious Adverse Event 
An adverse event is considered “serious” if, in the view of the investigator, it results in any of the following 
outcomes: 
 
• 
Death 
o 
If death results from (progression of) the disease, the disease should be reported as an 
event (SAE) itself. 
• 
A life-threatening adverse event 

HUM00199486 
________________________________________________________________________ 
 
 
20
o 
An adverse event is considered ‘life-threatening’ if, in the view of either the investigator 
[or sponsor], its occurrence places the patient or subject at immediate risk of death. It 
does not include an adverse event that, had it occurred in a more severe form, might 
have caused death.  
• 
Inpatient hospitalization or prolongation of existing hospitalization for > 24 hours. 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions 
• 
A congenital anomaly/birth defect 
• 
Important medical event 
o 
Any event that may not result in death, be life-threatening, or require hospitalization may 
be considered serious when, based upon appropriate medical judgment, they may 
jeopardize the patient and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition of “Serious Adverse Event”. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home; convulsions that do not result in inpatient hospitalization or 
the development of drug dependency or drug abuse. 
 
Hospital visits for conditions not associated with the urinary stone will not be collected or reported as 
SAEs.  
 
3. Expected Adverse Event 
An adverse event (AE) is considered “expected” if it meets the criteria of an AE per section 10.2, and is a 
known risk of general anesthesia and ureteroscopy such as: 
• 
Myocardial infarction, deep vein thrombosis, cerebrovascular accident, pulmonary embolism, 
fever, UTI, sepsis, perinephric hematoma, acute kidney injury, ureteral injury or perforation, 
ureteral stricture or scarring, stent migration or dislodgement, stent encrustation 
 
4. Unexpected Adverse Event 
An adverse event (AE) is considered “unexpected” if it meets the criteria of an AE per section 10.2, and is 
not expected as described above. 
 
Section 10.3: Reporting of Unanticipated Problems 
Upon becoming aware of any incident, experience, or outcome (not related to an adverse event) that may 
represent an unanticipated problem, the investigator should assess whether the incident, experience, or 
outcome represents an unanticipated problem. The incident, experience or outcomes is considered 
unanticipated if it meets all of the following criteria: 
1. Unexpected (in terms of nature, severity, or frequency); 
2. Related or possibly related to participation in the research; and 
3. Suggests that the research places subjects or others at a greater risk of harm than was previously 
known or recognized. 
 
If the investigator determines that the incident, experience, or outcome represents an unanticipated 
problem, the investigator must report it to the IRB according to the local IRB policies. 
 
Section 10.4: Unblinding Procedures 
To minimize bias in patient-reported outcome measures, all reasonable efforts will be made to keep 
patients blinded to their randomized treatment allocation. This will help to assure that all patient-reported 
outcomes and clinical data collection for the trial have been completed prior to unblinding. Patients will be 
notified of their randomized treatment allocation by trial staff at the coordinating center at the conclusion 
of the study. 
 
In the case of a medical emergency or other event in which the participant’s knowledge of their treatment 
allocation is critical to the participant’s clinical management, the blinding for that participant may be 
broken by the investigator. The investigator or their designee must document the date and reasons for 
such emergency unblinding in the participant’s source documents. The investigator must also 
immediately notify the study PI and trial coordinating center of such an event. 

HUM00199486 
________________________________________________________________________ 
 
 
21
  
 
Section 10.5: Stopping Rules  
An interim analysis for futility is planned after accrual of 112 patients. The study will stop early if it is found 
that the silicone stent arm has clinically significant worse pain intensity and worse pain interference at 7 
days with worse pain defined as 5 or greater t-score points worse pain in the silicone stent arm compared 
to the non-silicone stent arm after adjusting for baseline. Under the alternative hypothesis for both 
endpoints simulations of 1000 trials estimates the probability of stopping early is 0%. If we assume that 
the silicone stent is worse than the non-silicone stent by 5 points simulation of 1000 trials estimates the 
probability of stopping early is 24.4%. 
 
 
Section 11: STATISTICAL CONSIDERATIONS 
Section 11.1: Statistical Hypotheses 
This is a multi-center two-arm stratified, randomized comparative effectiveness study in patients are 
treated with URS for nephrolithiasis with a planned placement of a stent to assess patient reported quality 
of life.  The primary hypothesis is that the silicone ureteral stent arm will have superior patient reported 
pain outcomes compared to the non-silicone stent arm. Patients will be stratified by stone location (kidney 
only / ureteral) and randomized to receive a silicone stent or a non-silicone stent and complete the 
PROMIS® pain intensity and PROMIS® pain interference surveys prior to surgery and at 7 days after 
stent placement.   
 
Our formal statistical hypotheses are: 
 
H0: µns = µss,  
H1: µns ≠ µss 
 
where, µns = mean PROMIS® pain intensity in non-silicone stent arm at 7 days 
 
µss = mean PROMIS® pain intensity in silicone stent arm at 7 days 
AND 
 
H0: wns = wss   
H1: wns ≠ wss 
 
where, wns = mean PROMIS® pain interference in non-silicone stent arm at 7 days 
 
wss = mean PROMIS® pain interference in silicone stent arm at 7 days 
 
Section 11.2: Power/Sample Size: 
Assume that the correlation of baseline is 0 for purposes of the sample size calculation.  If this 
assumption is violated, the power for each hypothesis will be greater than the stated power.  
 
A clinically meaningful change in pain PROMIS® score is between 4 and 6 and the standard deviation of 
the score is 10(16-18). Assuming a 5 t-score PROMIS® pain point difference between 2 arms and a 
standard deviation of 10, a t-test including 101 patients per arm has 90% power with a 2-sided alpha = 
0.025. Assuming a 10% loss-to-follow-up, accrual of 224 study treated patients (112 patients per arm) is 
planned. Our planned analysis does not match this calculation because we will adjust for the baseline 
pain to ensure any imbalance prior to surgery is accounted for.  However, this power calculation, by 
ignoring the adjustment of baseline pain, is accurate if the correlation of baseline pain with our outcome is 
0. If the correlation is greater than 0, then we will have more power than described.(19)  
 
Section 11.3: Populations for Analyses 
Modified Intent-to-Treat (m-ITT) Population: All participants eligible and randomized who complete the 
pain intensity and pain interference questionnaire between 7-10 days post-URS will be included.  
Subjects will be analyzed by assigned treatment at randomization. This is the main population for efficacy 
analyses. 
 
Per-Protocol Population: All Patients eligible and randomized patients who complete the pain intensity 
and pain interference questionnaire between at 7 days post-URS will be included per treatment arm 
received. This second population will be used to assess the robustness of the primary and secondary 
efficacy outcomes. 
 

HUM00199486 
________________________________________________________________________ 
 
 
22
Safety Population: All patients who are randomized and receive a stent will be define the safety 
population and used for all safety analyses. Subjects will be analyzed by assigned treatment arm.  
 
Section 11.4: Statistical Analyses 
General Approach 
Descriptive statistics for the study population will be reported using frequentist statistics. In general, 
continuous measures will be reported using means and standard deviations or medians and the 
interquartile range as the distribution warrants. Categorical variables will be reported as counts and 
proportions.   
 
Analysis of the Primary Efficacy Endpoints 
The primary endpoints of the study are PROMIS® pain intensity and PROMIS® pain interference t-
scores. Each endpoint will be analyzed separately using an ANCOVA model for each. Using the mITT 
population for analysis, the t-score of the PROMIS® outcome at 7 days post-URS will be the dependent 
variable and treatment arm and pre-treatment (baseline) PROMIS t-score will be independent variables. 
The primary comparison of interest is treatment arm. The baseline adjusted mean pain score at 7-days 
will be reported by arm with the 97.5% confidence interval and a type-3 F-test will test the hypothesis that 
pain differs between the two treatment groups.  Each endpoint modeled will test the effect of treatment 
arm adjusting for baseline with a type I error of 2.5% for an overall study type I error of 5%.  
 
An analysis in the per-protocol population will be assess the robustness of the effect found in the primary 
analysis.  Additionally, a multivariable model will be considered to account for other patient or surgical 
variables that may be unbalanced between the arms including timing of stent removal or stone location. 
 
Analysis of the Secondary Endpoints 
Additional health-related quality of life endpoints including PROMIS® Pain scores at 4 weeks will be 
analyzed with similar models described for the primary endpoint. A linear mixed model will be used to 
compare LURN SI-10 scores at 7 days and 4 weeks between treatment arms. Each analysis will report 
means with 95% confidence intervals at each time for each arm with a model based type-3 F-test 
comparing treatment arms.  
 
Healthcare utilization within 30 days of URS will be assessed using a composite endpoint. The composite 
healthcare utilization metric within 30 days will be a composed score based upon utilization by the patient 
with each patient assigned a score based upon the highest utilization level that they participate in with 
levels defined in decreasing order:  
 
5. Hospitalization and ICU care 
4. Unplanned hospitalization 
3. Emergency department visit 
2. Ambulatory encounter: Clinic visit 
1. Ambulatory encounter: Phone call or message 
 
We will compare the composite score ranking between the treatment arms using a WinRatio analysis 
using the unmatched approach.(20) The median composite score for each arm will be reported, along 
with the WinRatio and associated 95% confidence interval and p-value. 
 
Abnormal imaging and stone-free rates will each be summarized as a count with the associated 
proportion by treatment arm and tested with a chi-square test (or fisher’s exact test if event counts are 5 
or less.) 
 
Planned Interim Analyses 
An interim analysis for futility is planned after accrual of 112 patients. The study will stop early if it is found 
that the silicon stent arm has clinically significant worse pain intensity and worse pain interference at 7 
days with worse pain defined as 5 or greater t-score points worse pain in the silicone stent arm compared 
to the non-silicone stent arm after adjusting for baseline. Under the alternative hypothesis for both 
endpoints simulations of 1000 trials estimatas the probability of stopping early is 0%. If we assume that 

HUM00199486 
________________________________________________________________________ 
 
 
23
the silicone stent is worse than the non-silicone stent by 5 points simulation of 1000 trials estimates the 
probability of stopping early is 24.4%. 
 
Sub-Group Analyses 
A sub-group analysis by stone location is planned. Primary and secondary endpoints will be reported for 
ureteral stones separately from renal stones. 
 
Exploratory Analyses.   
The mean (with standard deviation) or median (with interquartile range) days taken off work by patient 
and separately by caregiver will compared between treatment arms with a t-test or Wilcoxon rank test if 
the distribution warrants.  
 
Ecological Momentary Assessments of pain and PROMIS® daily ability to participate in social roles and 
activities score measured via daily text message will displayed using spaghetti plots. Each measure will 
be analyzed with a linear mixed model including fixed effects of treatment arm, day, and the interaction of 
treatment arm and day. As this is an exploratory endpoint, these models will be explored using several 
methods to address missing data and model fit.   
 
Each healthcare utilization metric within 30 days of URS will be summarized separately as a count with 
the associated proportion by treatment arm and tested with a chi-square test (or fisher’s exact test if event 
counts are 5 or less.)  
 
In an exploratory analysis to create a composite endpoint to be used in future trials we will assess the 
plausibility of 2 composite measurement plans and analyses of these. 
In addition to the WinRatio, our second composite analysis will include healthcare utilization and 
PROMIS® Pain. Additionally, we will use a composite score ranking of healthcare utilization similar to the 
WinRatio plan and add the PROMIS® Pain scores to the analysis using DOOR. The probability that a 
randomly selected patient will have a better DOOR if assigned to the silicone stent will estimated.(21) The 
WinRatio and DOOR composite healthcare utilization metric ratios' sizes and directions will be compared. 
 
The number and proportion of patients who are prescribed opioid medications will be reported by arm and 
compared using a chi-square test. 
 
Satisfaction score assessed using the ICIQ-S will be summarized at 7 days and 4 weeks by arm with 
means and standard deviations.  A repeated measures model will be used to test if satisfaction differed at 
either time between treatment arms using an interaction of time and arm.  
 
Section 12: DATA AND SAFETY MONITORING 
The DSMC will consist of the MUSIC ROCKS Program Manager, Program Director, Statistician, and other 
members of the MUSIC ROCKS team. This committee is responsible for monitoring the safety and data 
integrity of the study. 
 
Each performance site’s local study team is required to meet virtually with the DSMC and BLUES study 
team every six months if it is determined by the DSMC and/or Principal Investigator that a virtual 
meeting is necessary. The discussion may include matters related to the safety of study participants 
(Serious Adverse Event, Adverse Event and Unanticipated Problem reporting), completeness, validity 
and integrity of the study data, enrollment rate relative to expectations, characteristics of participants, 
retention of study participants, and adherence to the protocol (potential or real protocol deviations). If 
there are no concerns around any of the aforementioned items, the principal investigator and/or the 
DSMC may decide that a meeting is unnecessary and if so, a progress summary communication will 
serve in it’s place. Additionally, a member of the BLUES study team will send a communication 
summarizing current progress to each site on a monthly basis. These communications will consist of 1) 
any identified Serious Adverse Events and necessary follow-up, 2) enrollment rate relative to 
expectations, and 3) any identified protocol deviations, unanticipated problems, and recommendations 
to prevent additional instances. 
 

HUM00199486 
________________________________________________________________________ 
 
 
24
These 6-month meetings are to be documented by the BLUES study coordinator or the BLUES trial 
project manager and will include the topics listed above as appropriate. The meeting minutes must be 
signed by the Principal Investigator or by one of the co-investigators. 
 
The BLUES study team is responsible for collating all the meeting documentation for participating sites 
and will report any serious adverse events, unanticipated problems, and protocol deviations as outlined in 
section 10. 
 
 
Section 13: QUALITY ASSURANCE AND AUDITS 
The Data and Safety Monitoring Committee can request a ‘for cause’ quality assurance audit of the study 
if the committee identifies a need for a more rigorous evaluation of study-related issues. 
 
A regulatory authority (e.g. FDA) may also wish to conduct an inspection of the study, during its conduct 
or even after its completion. If an inspection has been requested by a regulatory authority, the site 
investigator must immediately inform the BLUES study team that such a request has been made. 
 
 
Section 14: CLINICAL MONITORING PROCEDURES 
Prior to subject recruitment, a participating site will undergo site initiation meeting to be conducted by the 
BLUES study team. This will be done as a teleconference, videoconference, or web-based meeting after 
the site has been given access to the study database, provided the BLUES study team the necessary 
regulatory documentation and received IRB approval. The site’s principal investigator and study staff 
should make every effort in attending the site initiation meeting. Study–related questions or issues 
identified during the site initiation meeting will be followed-up by the appropriate BLUES study team 
personnel until they have been answered and resolved. 
 
Monitoring of this study will include centralized surveillance of study specific MUSIC registry data by the 
BLUES study team to confirm adherence to the protocol. The BLUES study team will meet at least once 
per month to review findings of surveillance and may engage sites ad-hoc as appropriate. Additional 
monitoring will be performed by the BLUES study staff members on an annual basis.    
 
 

HUM00199486 
________________________________________________________________________ 
 
 
25
REFERENCES 
1. 
Saigal CS, Joyce G, Timilsina AR, Urologic Diseases in America P. Direct and indirect costs of 
nephrolithiasis in an employed population: opportunity for disease management? Kidney international. 
2005;68(4):1808-14. Epub 2005/09/17. doi: 10.1111/j.1523-1755.2005.00599.x. PubMed PMID: 
16164658. 
2. 
Oberlin DT, Flum AS, Bachrach L, Matulewicz RS, Flury SC. Contemporary surgical trends in the 
management of upper tract calculi. The Journal of urology. 2015;193(3):880-4. Epub 2014/09/16. doi: 
10.1016/j.juro.2014.09.006. PubMed PMID: 25219700. 
3. 
Metzler IS, Holt S, Harper JD. Surgical Trends in Nephrolithiasis: Increasing De Novo Renal 
Access by Urologists for Percutaneous Nephrolithotomy. Journal of endourology / Endourological Society. 
2021. Epub 2021/01/13. doi: 10.1089/end.2020.0888. PubMed PMID: 33430693. 
4. 
Geraghty RM, Jones P, Somani BK. Worldwide Trends of Urinary Stone Disease Treatment Over 
the Last Two Decades: A Systematic Review. Journal of endourology / Endourological Society. 
2017;31(6):547-56. Epub 2017/01/18. doi: 10.1089/end.2016.0895. PubMed PMID: 28095709. 
5. 
Hiller SC, Daignault-Newton S, Pimentel H, Ambani SN, Ludlow J, Hollingsworth JM, Ghani KR, 
Dauw CA. Ureteral Stent Placement following Ureteroscopy Increases Emergency Department Visits in a 
Statewide Surgical Collaborative. The Journal of urology. 2021:101097JU0000000000001653. Epub 
2021/02/04. doi: 10.1097/JU.0000000000001653. PubMed PMID: 33533636. 
6. 
Staubli SE, Mordasini L, Engeler DS, Sauter R, Schmid HP, Abt D. Economic Aspects of 
Morbidity Caused by Ureteral Stents. Urologia internationalis. 2016;97(1):91-7. Epub 2016/01/23. doi: 
10.1159/000443379. PubMed PMID: 26795568. 
7. 
Morgan MS, Antonelli JA, Lotan Y, Shakir N, Kavoussi N, Cohen A, Pearle MS. Use of an 
Electronic Medical Record to Assess Patient-Reported Morbidity Following Ureteroscopy. Journal of 
endourology / Endourological Society. 2016;30 Suppl 1:S46-51. Epub 2016/02/13. doi: 
10.1089/end.2016.0079. PubMed PMID: 26864676. 
8. 
Assimos D, Krambeck A, Miller NL, Monga M, Murad MH, Nelson CP, Pace KT, Pais VM, Jr., 
Pearle MS, Preminger GM, Razvi H, Shah O, Matlaga BR. Surgical Management of Stones: American 
Urological Association/Endourological Society Guideline, PART II. The Journal of urology. 
2016;196(4):1161-9. doi: 10.1016/j.juro.2016.05.091. PubMed PMID: 27238615. 
9. 
Pereira JF, Bower P, Jung E, Parkhomenko E, Tran T, Thavaseelan S, Pareek G. Ureteral 
stenting practices following routine ureteroscopy: an international survey. World journal of urology. 
2019;37(11):2501-8. Epub 2019/02/13. doi: 10.1007/s00345-019-02660-7. PubMed PMID: 30747279. 
10. 
Meier K, Hiller S, Dauw CA, Hollingsworth JM, Kim TK, Qi JI, Telang J, Ghani KR, Jafri SM. 
Understanding ureteral access sheath use within a statewide collaborative and its effect on surgical and 
clinical outcomes. Journal of endourology / Endourological Society. 2021. Epub 2021/04/09. doi: 
10.1089/end.2020.1077. PubMed PMID: 33827269. 
11. 
Scotland KB, Lo J, Grgic T, Lange D. Ureteral stent-associated infection and sepsis: 
pathogenesis and prevention: a review. Biofouling. 2019;35(1):117-27. Epub 2019/02/09. doi: 
10.1080/08927014.2018.1562549. PubMed PMID: 30732463. 
12. 
Wiseman O, Ventimiglia E, Doizi S, Kleinclauss F, Letendre J, Cloutier J, Traxer O. Effects of 
Silicone Hydrocoated Double Loop Ureteral Stent on Symptoms and Quality of Life in Patients 
Undergoing Flexible Ureteroscopy for Kidney Stone: A Randomized Multicenter Clinical Study. The 
Journal of urology. 2020;204(4):769-77. Epub 2020/05/05. doi: 10.1097/JU.0000000000001098. PubMed 
PMID: 32364838. 
13. 
Gadzhiev N, Gorelov D, Malkhasyan V, Akopyan G, Harchelava R, Mazurenko D, Kosmala C, 
Okhunov Z, Petrov S. Comparison of silicone versus polyurethane ureteral stents: a prospective 
controlled study. BMC urology. 2020;20(1):10. Epub 2020/02/06. doi: 10.1186/s12894-020-0577-y. 
PubMed PMID: 32013936; PMCID: PMC6998278. 
14. 
Tomer N, Garden E, Small A, Palese M. Ureteral Stent Encrustation: Epidemiology, 
Pathophysiology, Management and Current Technology. Reply. The Journal of urology. 
2021:101097JU0000000000001679. Epub 2021/02/17. doi: 10.1097/JU.0000000000001679. PubMed 
PMID: 33591806. 
15. 
Forbes C, Scotland KB, Lange D, Chew BH. Innovations in Ureteral Stent Technology. The 
Urologic clinics of North America. 2019;46(2):245-55. Epub 2019/04/10. doi: 10.1016/j.ucl.2018.12.013. 
PubMed PMID: 30961857. 

HUM00199486 
________________________________________________________________________ 
 
 
26
16. 
Borofsky MS, Lane GI, Neises SM, Portis AJ. Patient-Reported Outcomes Measurement System 
(PROMIS((R))) for Patients with Urolithiasis: Initial Report. The Journal of urology. 2017;198(5):1091-7. 
Epub 2017/06/08. doi: 10.1016/j.juro.2017.05.080. PubMed PMID: 28587919. 
17. 
Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, Ader D, Fries JF, Bruce B, Rose M, 
Group PC. The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an 
NIH Roadmap cooperative group during its first two years. Medical care. 2007;45(5 Suppl 1):S3-S11. 
Epub 2007/04/20. doi: 10.1097/01.mlr.0000258615.42478.55. PubMed PMID: 17443116; PMCID: 
PMC2829758. 
18. 
Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, Choi 
S, Cook K, Devellis R, DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P, Revicki D, Rose M, 
Weinfurt K, Hays R, Group PC. The Patient-Reported Outcomes Measurement Information System 
(PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-
2008. Journal of clinical epidemiology. 2010;63(11):1179-94. Epub 2010/08/06. doi: 
10.1016/j.jclinepi.2010.04.011. PubMed PMID: 20685078; PMCID: PMC2965562. 
19. 
Vickers AJ. The use of percentage change from baseline as an outcome in a controlled trial is 
statistically inefficient: a simulation study. BMC Med Res Methodol. 2001;1:6. Epub 2001/07/19. doi: 
10.1186/1471-2288-1-6. PubMed PMID: 11459516; PMCID: PMC34605. 
20. 
Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of 
composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012;33(2):176-82. Epub 
2011/09/09. doi: 10.1093/eurheartj/ehr352. PubMed PMID: 21900289. 
21. 
Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-
Stein C, Cosgrove SE, Fowler VG, Jr., Lautenbach E, Chambers HF. Desirability of Outcome Ranking 
(DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clinical infectious diseases : an 
official publication of the Infectious Diseases Society of America. 2015;61(5):800-6. Epub 2015/06/27. 
doi: 10.1093/cid/civ495. PubMed PMID: 26113652; PMCID: PMC4542892. 
 
 
 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
27
FIGURES 
Figure 1.  ROCKS PRO Questionnaire 
ROCKS PRO PROMIS® Pain Intensity and Interference 
 
ROCKS PRO LURN-S10 
 

HUM00199486 
________________________________________________________________________ 
 
 
28
 
ROCKS PRO ICIQ-S 
 
 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
29
ROCKS PRO Time Off Work 
 
 
 
 
ROCKS PRO USSQ 
 
 
Figure 2. Daily Ecological Momentary Assessment 
 
Visual Analog Pain Scale  
 
 
 
PROMIS® Ability to Participate in Social Roles and Activities – Short Form 4a Questionnaire 
 
 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
30
Figure 3. BLUES Patient Reported Outcomes: Flow Chart 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
31
Figure 4. BLUES Ecological Momentary Assessments (EMA) – Daily Text Survey: Flow Chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

HUM00199486 
________________________________________________________________________ 
 
 
32
APPENDICES 
Appendix 1. Heat map of appropriateness for ureteral stent omission after URS according to 
panelists 
 
 
 
UAS +, ureteral access sheath used. UAS -, no ureteral access sheath used. Frag +, basketable residual 
fragments left. Frag -, no basketable residual fragments left