The RELIEF™ Ureteral Stent - Assessment of Retrograde Urinary Reflux
Phase: NA
Conditions: Kidney Stone
Sponsor: University of California, San Diego

 
 
Office of IRB Administration (OIA) 
Biomedical Protocol for  
Interventional Research 
Version Date 12.08.21 
 
 
      Edited version of NIH-FDA Clinical Trial Template v1.07 
The RELIEF Ureteral Stent – Assessment of Retrograde Urinary 
Reflux 
Protocol Number: 809792 
Principal Investigator: Seth Bechis, MD, MS 
IDE Number: N/A (device is FDA approved) 
Sponsor: The Ureteral Stent Company 
Funded by: The Ureteral Stent Company 
Version Number:  1.1 
24 July 2024 
 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
  
 
ii 
Table of Contents 
1 
PROTOCOL SUMMARY .............................................................................................................................. 1 
1.1 
Synopsis ............................................................................................................................................... 1 
1.2 
Schema ................................................................................................................................................ 1 
1.3 
Schedule of Activities (SoA) .............................................................................................................. 2 
2 
INTRODUCTION ........................................................................................................................................... 2 
2.1 
Study Rationale ................................................................................................................................... 2 
2.2 
Background .......................................................................................................................................... 2 
2.3 
Risk/Benefit Assessment ................................................................................................................... 2 
2.3.1 
Known Potential Risks .................................................................................................... 3 
2.3.2 
Known Potential Benefits ............................................................................................... 3 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 3 
3 
OBJECTIVES AND ENDPOINTS ............................................................................................................... 3 
4 
STUDY DESIGN ............................................................................................................................................ 5 
4.1 
Overall Design ..................................................................................................................................... 5 
4.2 
Scientific Rationale for Study Design ............................................................................................... 6 
4.3 
Justification for Dose ............................................................................ Error! Bookmark not defined. 
4.4 
End of Study Definition ....................................................................................................................... 6 
5 
STUDY POPULATION ................................................................................................................................. 7 
5.1 
Inclusion Criteria ................................................................................................................................. 7 
5.2 
Exclusion Criteria ................................................................................................................................ 7 
5.3 
Lifestyle Considerations ..................................................................................................................... 7 
5.4 
Screen Failures ................................................................................................................................... 7 
6 
STUDY INTERVENTION ............................................................................................................................. 7 
6.1 
Study Intervention(s) Administration ................................................................................................ 7 
6.1.1 
Study Intervention Description ...................................................................................... 8 
6.1.2 
Dosing and Administration ............................................... Error! Bookmark not defined. 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................. 8 
6.2.1 
Acquisition and accountability ....................................................................................... 8 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................. 8 
6.2.3 
Product Storage and Stability ........................................................................................ 8 
6.2.4 
Preparation ....................................................................................................................... 8 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................................ 8 
6.4 
Study Intervention Compliance ......................................................................................................... 8 
6.5 
Concomitant Therapy ......................................................................................................................... 8 
6.5.1 
Rescue Medicine ............................................................... Error! Bookmark not defined. 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................................................................... 8 
7.1 
Discontinuation of Study Intervention .............................................................................................. 8 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................................ 9 
7.3 
Lost to Follow-Up ................................................................................................................................ 9 

 
 
  
 
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8 
STUDY ASSESSMENTS AND PROCEDURES ....................................................................................... 9 
8.1 
Efficacy Assessments ........................................................................................................................ 9 
8.2 
Safety and Other Assessments ...................................................................................................... 10 
8.3 
Adverse Events and Serious Adverse Events .............................................................................. 10 
8.3.1 
Definition of Adverse Events (AE) .............................................................................. 10 
8.3.2 
Definition of Serious Adverse Events (SAE) ............................................................. 10 
8.3.3 
Classification of an Adverse Event ............................................................................. 10 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 12 
8.3.5 
Adverse Event Reporting ............................................................................................. 12 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 12 
8.3.7 
Reporting Events to Participants ................................................................................. 12 
8.3.8 
Events of Special Interest ............................................................................................ 13 
8.3.9 
Reporting of Pregnancy ................................................................................................ 13 
8.4 
Unanticipated Problems ................................................................................................................... 13 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................................ 13 
8.4.2 
Unanticipated Problem Reporting ............................................................................... 13 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 14 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 14 
9.1 
Statistical Hypotheses ...................................................................................................................... 14 
9.2 
Sample Size Determination ............................................................................................................. 14 
9.3 
Populations for Analyses ................................................................................................................. 14 
9.4 
Statistical Analyses ........................................................................................................................... 14 
9.4.1 
General Approach ......................................................................................................... 14 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................ 15 
9.4.3 
Analysis of the Secondary Endpoint(s) ...................................................................... 15 
9.4.4 
Safety Analyses ............................................................................................................. 15 
9.4.5 
Baseline Descriptive Statistics .................................................................................... 15 
9.4.6 
Planned Interim Analyses ............................................................................................ 15 
9.4.7 
Sub-Group Analyses ..................................................................................................... 15 
9.4.8 
Tabulation of Individual participant Data .................................................................... 15 
9.4.9 
Exploratory Analyses .................................................................................................... 15 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 15 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .......................................................... 15 
10.1.1 
Study Discontinuation and Closure ............................................................................ 15 
10.1.2 
Confidentiality and Privacy ........................................................................................... 16 
10.1.3 
Future Use of Stored Specimens and Data ............................................................... 16 
10.1.4 
Key Roles and Study Governance .............................................................................. 16 
10.1.5 
Safety Oversight ............................................................................................................ 17 
10.1.6 
Clinical Monitoring ......................................................................................................... 17 
10.1.7 
Data Handling and Record Keeping ........................................................................... 17 
10.1.8 
Protocol Deviations ....................................................................................................... 18 

 
 
  
 
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10.2 
Additional Considerations ................................................................................................................ 18 
10.3 
Abbreviations ..................................................................................................................................... 19 
10.4 
Protocol Amendment History .......................................................................................................... 21 
11 
REFERENCES ............................................................................................................................................ 22 
 

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PROTOCOL SUMMARY 
Leave blank. Text should be included under the relevant subheadings below. 
1.1 
SYNOPSIS  
Title: The RELIEF Ureteral Stent vs. Standard DJ Stent – Assessment of Retrograde Urinary Reflux 
Study Description: Assessment of retrograde urine reflux after placement of the RELIEF® Ureteral Stent 
using cystography after contrast gravity-filling of the bladder and assigning a urinary reflux grade. 
Randomized controlled trial for evaluation of the stent placement and the adequacy of short-term 
drainage (defined as the presence of the stent in the ureter and the lack of surgical or other 
intervention to treat symptoms associated with the stent itself on the stented side during the first 48 
hours). 
Primary Objective: Assessment of retrograde urine reflux after placement of a ureteral stent using 
cystography after contrast gravity-filling of the bladder and assigning a urinary reflux grade based on 
standard scoring. 
Secondary Objectives: Assessment of stent symptoms (incidence, relationship to device, severity) 
attributed to the ureteral stent; Reporting the Ureteral Stent Symptoms Questionnaire (USSQ) before 
stent placement, after placement at day 3, prior to removal and post removal; Visualization of distal 
coil floating in bladder (Y/N) after stent placement 
 
Primary Endpoint: Study success defined as adequate short-term drainage defined as the presence of 
the stent in the ureter and the lack of surgical or other intervention to treat symptoms associated with 
the stent itself on the stented side during the first 48 hours [Day 0-2] following placement. 
Secondary Endpoints: USSQ Scale (Ureteral Stent Symptoms Questionnaire) [Time Frame: Day 3 as 
endpoint, Unplanned hospital visits or doctor visits related to the stent, Medication use 
 
 
 
Description of Sites/Facilities Enrolling Participants: UC San Diego 
   
Description of Study Intervention: Randomized Controlled Trial 
 
Study Duration: 1 year 
Participant Duration: 1 year 
 
 
 
1.2 
SCHEMA 
See section 1.3 
 
 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening/Enrollment 
Day -90 to -1 
Stent Placement     
(Day 0) 
Post-Stenting, Visit 1 
(Day 1) 
Follow up Phone call 
(Day 3) 
Stent Removal        
(Day 7-10) 
2-days Post Stent 
Removal 
(Day 9-12) 
Informed consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medication Review 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
Ureteral Stent Symptoms 
Questionnaire 
 
 
X 
X  
X  
X 
RELIEF Ureteral Stent or DJ 
Stent  
 
X (placement per 
standard of care) 
 
X (removal per 
standard of care) 
 
 
Intraoperative Post Stent Photo 
 
X 
 
 
X 
 
Adverse event review and 
evaluation 
 
X 
X 
X 
X 
X 
Clinical Usability Survey 
 
X 
 
 
 
 
 
 
2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Traditional ureteral stents are commonly used in practice to relieve renal obstruction or as a scaffold to 
promote healing after endoscopic or open/ laparoscopic surgeries involving the ureter [1]. However, 
morbidities can be associated with placing these stents such as pain or irritative bladder symptoms, 
which are felt in part to be due to urinary reflux up the stent. The RELIEF stent has the potential to 
improve urinary symptoms due to its unique structural design, which allows the ureteral orifice to close 
naturally and reduce the reflux of urine back into the kidney. This study seeks to assess whether the 
RELIEF stent has less reflux and, therefore, less irritative symptoms. 
 
2.2 
BACKGROUND  
The most commonly reported symptoms include urgency, urinary frequency, dysuria, incontinence, 
hematuria, suprapubic discomfort, fever due to urinary tract infections and flank pain and they can 
occur in up to 80% of stented patients.  Sometimes, the symptoms are poorly tolerated and can 
negatively affect the patient’s quality of life [2, 3]. 
 
Shao et al have studied the relationship between bladder filling and the renal pelvic pressure (RPP) in 
stented patients, which revealed that RPP increases mildly during bladder filling and dramatically during 
voiding, indicating the occurrence of urinary reflux. As a result, the authors encouraged early removal of 
the stents [4]. Another study showed that patients with stents whose distal coils cross the midline are at 
higher risk of post-stenting morbidities [5].  
 
2.3 
RISK/BENEFIT ASSESSMENT   
 

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2.3.1 KNOWN POTENTIAL RISKS  
There is a potential risk of loss of confidentiality of data.  Every effort will be made to keep the patients’ 
information confidential. 
 
The study participants may feel uncomfortable while addressing some of the questions in the pain 
questionnaire.  They may refuse to answer any of these questions. They may stop their participation in 
this study at any time. 
 
The standard of care surgical risks and risks with either of the stents should have been reviewed with 
their surgeon. 
 
Patients who participate in this research study will not get to select the type of stent they will receive. 
  
The principal investigator for this research project has determined and verified that all imaging scans 
prescribed for this project would typically be performed as part of the standard medical care required to 
adequately monitor the participant’s current illness. If they are especially concerned with radiation 
exposure, or they have had a lot of x-rays or imaging scans already, they should discuss this with the 
principal investigator for this project, Dr. Bechis, or their regular doctor. 
 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
There is potential direct benefit for the patients assigned to the RELIEF stent group as we suspect it will 
provide relief from discomfort during recovery after ureteroscopy. The knowledge to be gained from 
this research is whether the Relief stent reduces urinary reflux and decreases postoperative pain and 
discomfort for patients who undergo kidney stone surgery and stent placement. If the Relief stent 
provides improvement in symptoms, this will improve patient care and comfort. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
The group of investigators, including the principal investigator, and the research support staff will 
monitor for adverse events. Data will be reviewed quarterly to ensure it is accurate, complete, and its 
collection complies with the protocol. There will also be a continual assessment of the risks and benefits. 
  
 
 
Furthermore, Case report forms will be generated for each subject and completed by the investigator or 
study coordinator. The investigator or study coordinator will countersign each form. After the case 
report forms for a visit are completed, the research coordinator will enter a limited set of data into a 
Redcap data management system. Original case report forms will be securely maintained at the clinical 
sites. Completed copies of the case report forms will be sent to the research coordinator where they will 
be stored on a secure hard drive. Subjects will be asked to report any adverse events to the study 
coordinator or physician. All adverse events will be reported on a standardized form that will elicit the 
number and specify the type of tests used, therapy (or therapies) used, and clinical visits (office, ER and 
hospitalization) required until the event is resolved. 
 
 
3 
OBJECTIVES AND ENDPOINTS 
We hypothesize that the RELIEF stent will offer the same function as a traditional stent with the added 
benefits of 1) prevention of urinary reflux and 2) reduction of irritative bladder symptoms. 

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Primary Objectives:  
• 
Assessment of retrograde urine reflux after placement of a ureteral stent using cystography 
after contrast gravity-filling of the bladder and assigning a urinary reflux grade based on the 
following standardized scoring system: 
- 
Grade I: urine refluxes into the ureter only. 
- 
Grade II: urine refluxes into the ureter and up to the kidney without dilation. 
- 
Grade III: urine refluxes into the ureter and kidney and causes mild dilation. 
- 
Grade IV: urine refluxes into ureter and kidney and causes dilation without twisting of the 
ureter. 
- 
Grade V: urine refluxes into ureter and kidney and causes significant dilation with twisting of 
the ureter. 
 
• 
Evaluation of the stent placement and the adequacy of short-term drainage (defined as the 
presence of the stent in the ureter and the lack of surgical or other intervention to treat 
symptoms associated with the stent itself on the stented side during the first 48 hours). 
 
Secondary Objectives: 
• 
Assessment of pain or irritative symptoms attributed to the ureteral stent as well as unplanned 
return visits to ED, OR, or clinic. 
• 
Reporting the Ureteral Stent Symptoms Questionnaire (USSQ) before stent placement, after 
placement at day 3, prior to removal and post removal. 
• 
Visualization of distal coil floating in bladder (Y/N), after stent placement. 
 
Study Endpoints: 
1- Primary effectiveness endpoint:  
• 
Study success defined as adequate short-term drainage defined as the presence of the stent in the 
ureter and the lack of surgical or other intervention to treat symptoms associated with the stent 
itself on the stented side during the first 48 hours [Day 0-2] following placement.   
• 
[Note: In some cases, the ureteral stent may not be sufficient to relieve pain (not associated with 
stent specifically) and alternative surgical treatment may be warranted. In these cases, patient 
data will be captured but non-device related cause captured as reason for subject stenting 
termination.] 
• 
Assessment of retrograde urine reflux after placement of the ureteral stent, as determined by the 
visualization of urine in the distal ureter to the kidney using cystography after contrast gravity-
filling of the bladder and assigning a urinary reflux grade based on: 
- 
Grade I: urine refluxes into the ureter only. 
- 
Grade II: urine refluxes into the ureter and up to the kidney without dilation. 

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- 
Grade III: urine refluxes into the ureter and kidney and causes mild dilation. 
- 
Grade IV: urine refluxes into ureter and kidney and causes dilation without twisting of the 
ureter. 
- 
Grade V: urine refluxes into ureter and kidney and causes significant dilation with twisting of 
the ureter. 
 
 
• 
Visualization of distal coil in bladder, after stent placement. Document placement using a 
cystoscope. 
 
2- Primary safety endpoint:  
Assessment of pain or irritative symptoms (incidence, severity) attributed to the ureteral stent 
as well as unplanned return visits to ED, OR, or clinic. 
3- Secondary endpoint: 
• 
USSQ Scale (Ureteral Stent Symptoms Questionnaire) [Time Frame: Day 3 as endpoint 
• 
Unplanned hospital visits or doctor visits related to the stent 
• 
Medication use endpoint:   
o Physicians can prescribe standard medications such as alpha blocker (Tamsulosin), 
Anticholinergic (Oxybutynin), phenazopyridine (Pyridium), ibuprofen and Tylenol prn 
pain for the duration of the stent plus 1 day (post stent removal) (Document on CRF) 
o Requests for “breakthrough” pain medication (narcotics) would be at the request of the 
patient post procedure (not to be given as a standard dose). (Document on CRF) 
o Patients to keep medication diary in situations where patients are not taking 
medications as prescribed 
o Use of medication (amount and type of medication) will be analyzed between the 
RELIEF stent and DJ Stent groups, including calculation of cost of medications between 2 
groups 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
Allocation: Randomized 1:1 RELIEF stent vs. DJ Stent 
Endpoint Classification: Comparison Study 
Intervention Model: Two Group Assignment 
Masking: Open Label 
Primary Purpose: Treatment 

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Patients will undergo their scheduled ureteroscopy with laser lithotripsy and ureteral stent placement 
per standard of care methods. 
 
Screening/Enrollment: 
• 
Patients will be screened for eligibility 
• 
If eligible, patients will be enrolled in the study through signing of the Informed Consent Form 
• 
Medical charts will be reviewed, demographics will be collected, and medications will be 
reviewed prior to surgery 
 
Day 0 (Stent Placement) 
• 
Patients will be randomized to one of two study groups (Relief stent vs DJ stent) 
• 
Medical charts will be reviewed and medications will be reviewed prior to surgery 
• 
Stent will be placed per standard of care 
• 
A intraoperative photo of the stent will be taken to confirm placement 
 
Post-stent Follow-Up: 
• 
Post-operatively complete Ureteral Stent Satisfaction Questionnaire (USSQ) surveys at day 1, day 
3, day of stent removal, and 2 days post stent removal (note day of removal) (between 7-10 days 
in normal practice (even up to 14 days): 
• 
Medications will be tracked on the CRF at day 1, day 3, day of stent removal, and 2 days post stent 
removal  
• 
Day 1 (12-30 hours after stenting procedure), subject will be evaluated by study personnel for 
acceptable procedural outcome. 
• 
Document any unplanned hospital visits or doctor visits related to the stent 
Day 1, Day 3, Day of stent removal (i.e., Day 7-10), and 2 days post stent removal, subject will be 
evaluated by study personnel for ongoing tolerability and stent performance (e.g., drainage) in 
person or by phone. 
• 
Direct or remote evaluation will be documented. If unusual levels of pain or other potentially 
serious complications are suspected, the subject will be brought in for Clinician evaluation. 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
We seek to compare the Relief stent to our currently used ureteral stent to determine if it offers 
improved clinical outcomes. To this end, patients will be randomized to receive either the Relief stent or 
the standard stent and the prospectively collected data will be analyzed and compared. At our target 
enrollment of 50 patients (25 patients in each arm), a power analysis for our primary endpoint 
(differences in incidence of retrograde urine reflux between randomized study arms) determined that 
our study will be sufficiently powered (80%) to detect a moderate effect size (w = 0.4) at an alpha level 
of 0.05. 
 
4.3 
END OF STUDY DEFINITION 
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 Schedule of Activities (SoA), 
Section 1.3. 
 

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The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial 
globally. 
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
To be eligible to participate in this study, an individual must meet all the following criteria: 
1. Has capacity to consent 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study  
3. Persons, 18 years of age or older 
4. Male or female subjects with confirmed ureteral and/or renal stones or strictures documented 
via abdomen X-ray KUB (kidney ureter bladder) or CT (computed tomography) 
 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Distal ureteral obstruction where suture portion of stent may be placed 
2. Urinary reflux (assessed by pre-stent cystogram) 
3. Pregnancy or lactation 
4. Patients requiring bilateral surgical stone management procedure 
5. Infected stones 
6. Patients where 24cm or 26cm stent lengths are not suitable 
7. Ureteral structure in distal third of ureter 
8. Intraoperative exclusion: based on urologist’s discretion, if trauma has been induced to the 
distal ureter due to ureteroscopy maneuvers, exclude these patients 
 
5.3 
LIFESTYLE CONSIDERATIONS 
N/A 
 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a stent 
contraindication may be rescreened. Rescreened participants should be assigned the same participant 
number as for the initial screening. 
 
6 
STUDY INTERVENTION 
  
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 

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6.1.1 STUDY INTERVENTION DESCRIPTION 
The study intervention is placement of the RELIEF Ureteral Stent, and the control product is the Ascerta 
stent by Boston Scientific. Placement of the stent is described in section 4 of the protocol. 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
The Relief stent is provided from the company at no charge. The control stent is our current standard 
stent (Ascerta by Boston Scientific) which is available in stock. Both will be kept in an OR storage 
location, and the Relief stent will have a notice that it is for research purposes and not to be used 
outside of this study and without instruction by the study PI and coordinator. 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Both the Relief stent and control stent are supplied in standard sterile packaging. 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
The stents will be stored in the usual location where Urology disposable products are kept. 
 
6.2.4 PREPARATION 
No preparation is required. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Patients will be randomized to receive either the Relief stent or the standard ureteral stent. The 
randomization sequence will be computer-generated, and patients will be randomly allocated based on 
this sequence. 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
There will be three questionnaires completed by subjects at multiple different timepoints which will 
ensure study invention compliance. 
 
6.5 
CONCOMITANT THERAPY 
N/A 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Discontinuation from having the stent placed for the expected duration of 7-14 days does not mean 
discontinuation from the study, and remaining study procedures should be completed as indicated by 
the study protocol.  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 as an adverse 
event (AE). 

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The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Detailed reason for early or late stent removal 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
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: 
• 
Pregnancy 
• 
Significant study intervention non-compliance  
• 
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 
The reason for participant discontinuation or withdrawal from the study will be recorded on the 
Withdrawal Case Report Form (CRF). Research participants who sign the informed consent form and are 
randomized but do not receive the study intervention may be replaced.  Research participants 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. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for 3 scheduled visits and is 
unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
EFFICACY ASSESSMENTS  
The primary objective of the study is to assess whether the Relief stent causes reflux of urine. This will 
be assessed using a standardized grading system described previously. The additional objective of 
evaluating adequacy of short-term drainage uses the following definition: presence of stent in the ureter 
and lack of surgical or other intervention to treat symptoms associated with the stent itself during the 
first 48 hours. This will be determined during the phone interview or in person visit with the patient on 

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days 1 and 3 as well as by questionnaire. Medications used will be tracked on the research form per the 
timeline at days 1, 3, 7-10. 
 
Screening will occur in the clinics to identify patients with stone disease who meet eligibility 
requirements and who require surgical treatment for their stones. 
 
Patients who are deemed clinically suitable and choose to participate will be screened utilizing the EMR 
for recruitment. The urology provider will first determine if they are interested in participating in the 
research study and upon agreement, a study team member or research coordinator will introduce the 
study details and initiate a consent interview. If eligible, these patients will be approached during pre-
surgical preoperative clinic visits by the research team to further explain the study and further address 
any of their questions and get their consent. Patients will be free to leave the study without any impact 
or influence on their clinical care or management at any point should they desire to do so. 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
Case report forms will be generated for each subject and completed by the investigator or study 
coordinator. The investigator or study coordinator will countersign each form. After the case report 
forms for a visit are completed, the research coordinator will enter a limited set of data into a data 
management system. Original case report forms will be securely maintained at the clinical sites. 
Completed copies of the case report forms will be sent to the research coordinator where they will be 
stored on a secure hard drive. Subjects will be asked to report any adverse events to the study 
coordinator or physician. All adverse events will be reported on a standardized form that will elicit the 
number and specify the type of tests used, therapy (or therapies) used, and clinical visits (office, ER and 
hospitalization) required until the event is resolved. 
 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
The FDA definition of an Adverse event is any untoward medical occurrence associated with the use of 
an intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)).  
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events 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 participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 

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8.3.3.1 SEVERITY OF EVENT 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines 
will be used to describe severity.  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial, the 
study product must always be suspect.  
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study intervention (DE challenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within 
a reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of the 
study intervention) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
8.3.3.3 EXPECTEDNESS  

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The study PI and Sponsor will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The study coordinator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
8.3.5 ADVERSE EVENT REPORTING  
The group of investigators, including the principal investigator, and the research support staff will carry 
out monitoring of all AEs. These will be captured on the appropriate case report form (CRF). Data will be 
reviewed quarterly to ensure that it is accurate, complete, and that its collection is in compliance with 
the protocol. There will also be a continual assessment of the risks and benefits. 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the 
study sponsor and to the reviewing Institutional Review Board (IRB) as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the effect.  The study sponsor is 
responsible for conducting an evaluation of an unanticipated adverse device effect and shall report the 
results of such evaluation to the Food and Drug Administration (FDA) and to all reviewing IRBs and 
participating investigators within 10 working days after the sponsor first receives notice of the effect. 
Thereafter, the sponsor shall submit such additional reports concerning the effect as FDA requests. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
N/A 

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8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
 
8.3.9 REPORTING OF PREGNANCY  
N/A 
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
This definition could include an unanticipated adverse device effect, any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)). 
 
8.4.2  UNANTICIPATED PROBLEM REPORTING  
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB). The UP report will include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:  
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB as soon as possible, but in 
no event later than 10 working days after the investigator first learns of the event. 
• 
Any other UP will be reported to the IRB and to the study sponsor within 3 days of the 
investigator becoming aware of the problem.  

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• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within 24 hours of the IRB’s receipt of the report of the 
problem from the investigator. 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
Cystogram and stent placement are standard urologic procedures. Outcomes from the surgical 
procedure will be communicated to the patient or their designated family member per standard practice.  
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
Primary Efficacy Endpoint: presence of reduced ureteral reflux in Relief stent compared to standard 
ureteral stent. 
Comparative statistics will be employed between the two groups. Findings will be reported as the median 
and interquartile range (IQR) for continuous variables, and percentages and frequencies for categorical 
variables. To evaluate difference in the incidence of retrograde reflux (primary endpoint: present, absent) 
and grading between both arms (primary endpoint; Grades I, II, III, IV, V) Chi-square or Fishers exact 
test will be used as appropriate. 
 
9.2 
SAMPLE SIZE DETERMINATION 
At our target enrollment of 50 patients (25 patients in each arm), a power analysis for our primary 
endpoint (differences in incidence of retrograde urine reflux between randomized study arms) 
determined that our study will be sufficiently power (80%) to detect a moderate effect size (w = 0.4) at 
an alpha level of 0.05. 
 
9.3 
POPULATIONS FOR ANALYSES 
To be eligible to participate in this study, an individual must meet all the following criteria: 
1. Those who have capacity to consent 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study  
3. 18 years of age and up 
4. Male or female subjects with confirmed ureteral and/or renal stones or strictures documented 
via abdomen X-ray KUB (kidney ureter bladder) or CT (computed tomography) 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
Findings will be reported as the median and interquartile range (IQR) for continuous variables, and 
percentages and frequencies for categorical variables. To evaluate differences in the incidence of 
retrograde reflux (Primary endpoint; present, absent) and grading between both arms (Primary 
endpoint; grades I, II, III, IV, V), chi-square or fishers exact test will be used as appropriate. To analyze 
USSQ findings between study arms (secondary endpoint), Mann-Whitney U test or independent t-tests 
will be used for comparisons of continuous variables and chi-square or fishers exact test for comparisons 
of categorical variables.  

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9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
To evaluate differences in the incidence of retrograde reflux (Primary endpoint; present, absent) and 
grading between both arms (Primary endpoint; grades I, II, III, IV, V), chi-square or fishers exact test will 
be used as appropriate. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
To analyze USSQ findings between study arms (secondary endpoint), Mann-Whitney U test or 
independent t-tests will be used for comparisons of continuous variables and chi-square or fishers exact 
test for comparisons of categorical variables. 
 
 
9.4.4 SAFETY ANALYSES 
Adverse events and serious AEs will be compared between the two cohorts using descriptive and 
quantitative statistics, and the data will be presented in a table. 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Baseline descriptive statistics will be performed comparing the two cohorts. 
 
9.4.6 PLANNED INTERIM ANALYSES  
N/A 
 
9.4.7 SUB-GROUP ANALYSES 
Patients will be randomized to receive either the Relief stent or the current standard stent. Patients will 
be randomized regardless of age, sex, race/ethnicity or other demographic characteristic since stone 
disease and stent related pain affects patients of all genders. 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be listed by measure/time point; rather the data of the entire cohort 
will be presented I a de-identified way.  
 
9.4.9 EXPLORATORY ANALYSES 
N/A 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to investigator, funding agency, the Investigational 
New Drug (IND) or Investigational Device Exemption (IDE) sponsor and regulatory authorities.  If the 
study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform study 
participants, the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for the 

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termination or suspension.  Study participants will be contacted, as applicable, and be informed of 
changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
10.1.2 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be stored in Redcap. This will not include the participant’s contact or identifying information. Rather, 
individual participants and their research data will be identified by a unique study identification number. 
The study data entry and study management systems will be secured and password protected.  
 
10.1.3 FUTURE USE OF STORED SPECIMENS AND DATA  
Data collected for this study will be analyzed and stored at UCSD. After the study is completed, the de-
identified, archived data will be stored in RedCap.  
 
10.1.4 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator 

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Seth Bechis, MD, MS, Associate 
Professor of Urology 
UC San Diego Health 
200 W Arbor Dr. San Diego, CA 
92103 
858-657-7876 
sbechis@health.ucsd.edu 
 
10.1.5 SAFETY OVERSIGHT 
The group of investigators, including the principal investigator and the research support staff will carry 
out the Data and Safety Monitoring Plan. Data will be reviewed quarterly to ensure that it is accurate, 
complete, and that its collection is in compliance with the protocol. There will also be a continual 
assessment of the risks and benefits. 
 
10.1.6 CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).  
 
10.1.7 DATA HANDLING AND RECORD KEEPING  
 
10.1.7.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into a Redcap database. The data system includes 
password protection and internal quality checks, such as automatic range checks, to identify data that 
appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents. 
 
10.1.7.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harmonisation (ICH) region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 

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formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform 
the investigator when these documents no longer need to be retained. 
 
10.1.8 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 7 working days of identification of the protocol deviation, or within 7 working days of 
the scheduled protocol-required activity.  Protocol deviations must be sent to the reviewing Institutional 
Review Board (IRB) per their policies. The site investigator is responsible for knowing and adhering to 
the reviewing IRB requirements. Further details about the handling of protocol deviations will be 
included in the MOP. 
10.2 ADDITIONAL CONSIDERATIONS 
N/A 
 

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10.3 ABBREVIATIONS 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 

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UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
1- Chew, B.H., B.E. Knudsen, and J.D. Denstedt, The use of stents in contemporary urology. Current 
opinion in urology, 2004. 14(2): p. 111-115. 
2- Joshi, H., et al., Characterization of urinary symptoms in patients with ureteral stents. Urology, 
2002. 59(4): p. 511-516. 
3- Chambade, D., et al., Study of the safety of double J ureteric stents. Progres en urologie: journal 
de l'Association francaise d'urologie et de la Societe francaise d'urologie, 2006. 16(4): p. 445-
449. 
4- Shao, Y., et al., The influence of ureteral stent on renal pelvic pressure in vivo. Urological 
research, 2009. 37(4): p. 221-225. 
5- Giannarini, G., et al., Predictors of morbidity in patients with indwelling ureteric stents: results 
of a prospective study using the validated Ureteric Stent Symptoms Questionnaire. BJU 
international, 2011. 107(4): p. 648-654. 
6- Krebs, A., et al., The ‘buoy’stent: evaluation of a prototype indwelling ureteric stent in a porcine 
model. BJU international, 2009. 104(1): p. 88-92.