A Prospective Double Blind Randomized Control Trial Comparing Opioid to Non-Opioid Protocol in Managing Postoperative Pain After Ureteroscopy With Stent Placement
Phase: PHASE4
Conditions: Kidney Stone
Sponsor: Wake Forest University Health Sciences

Protocol version: 2 
Updated 9-9-19 
1 
Study Title: A prospective double blind randomized control trial comparing 
the standard-of-care (SOC) prescription analgesic to an over-the-counter 
(OTC) analgesic protocol in managing postoperative pain after ureteroscopy 
with stent placement 
 
NCT: NCT03872843 
 
Date:  9.9.19 
 
Principal Investigator: Jorge Gutierrez-Aceves 
 
Co-investigator(s): Ilan Klein, Taylor peak, Teresa Biles  
 
Sponsor or funding source: Departmental 
 
Background, Rationale and Context 
Ureteral stent placement is one of the most frequent procedures that we as urologists perform, 
especially in the field of stones in the urinary tract. The term "stent" refers to a thin tube that we 
place within the lumen of the ureter to maintain its patency, permit healing or relieve an 
obstruction. The most common type of stent we use is the “double J stent,” which was described 
in 1978 by Finney and has a proximal curl that is situated in the renal pelvis and a distal curl that 
is situated in the urinary bladder to keep the stent in place1.  
 
The current AUA/Society of Endourology guidelines published in 2016 state that it is reasonable 
to not stent patients after an ureteroscopy (URS) if they do not have a suspected ureteral injury, 
have no evidence of stricture or anatomic abnormality, have a normal contralateral kidney and 
normal renal function, and are not anticipated to need a second procedure2. But, truth be told, the 
majority of patients that undergo a URS end up with having a stent placed.  
Despite their great value and common use in the field of urology, stents have several common 
side effects. These include infection, encrustation necessitating replacement, hematuria, stent 
pain and bothersome lower urinary tract symptoms (LUTS), which are estimated to affect at least 
80% of patients who have an indwelling ureteral stent placed3. These symptoms include 
frequency, urgency, dysuria, incomplete emptying, flank pain, suprapubic pain, and 
incontinence. 
 
There are several mechanisms that have been postulated as the cause of stent-related pain 
and voiding symptoms. The stent-related flank pain and renal colic can be secondary 
to reflux of urine through the stent during voiding, when intravesical pressures increase with 
contraction that transmits the increased pressures to the renal collecting system and ultimately 
resulting in flank pain4. There is also the issue of stent movement with patient's activity and stent 
position that are thought to be additional sources of pain and lower urinary tract symptoms due to 
direct irritation of the bladder mucosa5,6.  
 
One of the tools that has helped to standardize research on stent related complications is the 
ureteral stent symptoms questionnaire (USSQ) that Joshi and colleagues described in 20037. This 
questionnaire consists of 38 items split into 6 sections: pain, voiding symptoms, work 
performance, sexual matters, overall general health, and additional problems.  

Protocol version: 2 
Updated 9-9-19 
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Several medications have been tried and studied in an attempt decrease stent-related symptoms 
after placement. Nonsteroidal anti- inflammatory drugs (NSAIDs) and narcotic/opioid analgesics 
can be helpful for the pain, but do not have any impact on the voiding symptoms, for which the 
primary medications used are alpha-blockers and antimuscarinic and the AUA/Society of 
Endourology Guidelines lists providing these medications to patients to help reduce stent 
discomfort as a moderate recommendation with level B evidence2. 
In the United States, there is a known raging opioid abuse epidemic fueled by prescription 
medications and resulting in significant strain on our healthcare system. There is increasing 
evidence that prescribers are at least partly responsible for the opioid crisis because of 
overprescribing, in part due to the concern that uncontrolled pain after surgical procedures will 
result in poor patient satisfaction and increased workload for ancillary staff.8  
Currently, there is a paucity of literature on analgesic requirements after URS for nephrolithiasis. 
It is critical that we as urologists and prescribers find a way to stop the needless overprescribing 
while still treating postoperative pain appropriately. 
As such, efforts have recently begun to implement non-opioid protocols for outpatient urologic 
surgeries, but the majority of them retrospective.9,10 
 
Our study objective is to evaluate the feasibility of a narcotic-free protocol in the management of 
postoperative pain after URS with stent placement and compare it to the current standard of care  
in our practice that does include opioids.  
 
In our study, we propose to randomize 100 patients that undergo an outpatient URS for renal 
stones with stent placement into the two arms once being discharged, in a double blinded 
fashion, either with ibuprofen 400mg or Norco 5/325mg for pain management. Both being 
scheduled QID prn pattern until the stent will be removed in our clinic a week later. This type of 
study has never been performed before in the United States and could potentially change 
treatment patterns for this common problem.   
 
Objectives 
1. Primary Objective – To determine that a non -narcotic/opioid protocol for pain 
management can be implemented for URS outpatient stented patient population common 
to the United States.  
2. Secondary Objective – To compare number of visits to the ED for postoperative 
genitourinary symptoms and pain, monitor number of telephone calls to the clinic, and 
requests for prescription pain medication refills of opioid Vs. non-opioids discharged 
patients.  
 
Methods and Measures 
 
Design 
This will be a randomized double blinded control trial with subjects randomized to either the 
WFBH Urology practice’s  standard of care pain-relief narcotic/opioid group (Norco 5-325 mg) 
or an available over-the-counter non-opioid group (Ibuprofen 400 mg).  Patients will be enrolled 
who are seen in the Urology Clinic at 140 Charlois Blvd.  Those subjects with a renal stones who 
are consented for a ureteroscopy will be eligible for the study. Subjects eligible for the study will 
have a discussion with the study team member about their treatment options.  They will be told 

Protocol version: 2 
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that the standard of care analgesic that is provided to patients undergoing ureteroscopy with stent 
placement is Norco.  They will be informed that if they choose to take part in the study they will 
be randomized to receive the SOC medication (Norco), or they may receive OTC Ibuprofen 
which is a nonsteroidal anti-inflammatory medication.  They can either elect not to be in the 
study and actively choose which treatment they would like, or they can choose to enter the study 
and be randomized to one of these treatment arms.   
 
If the subject chooses to be enrolled in the study, they will sign the consent form for 
participation, as well as surgical consent form for URS. Randomization will be performed by the 
Investigational Drug Study pharmacy on the 10th floor of the Cancer Center and will occur prior 
to the surgical date chosen by the surgeon and the patient.  Randomization will be performed 
using a random number generator.  
 
The URS will be performed using standard of care instruments and techniques.  No changes to 
operative technique will be performed for subjects in the study vs regular patients undergoing the 
same procedure. Post operatively; we plan to discharge all subjects home from the recovery unit.  
Hospital pharmacy will coat and prepare the generic medication and distribute the medication to 
the patients before they are discharged from the outpatient PACU.  
  
All subjects will be seen one week after surgery for follow up, questioner filling and stent 
removal. At that point the remaining study medication will be returned as will information about 
ED visits and pain medication refilled will be collected as well.   
 
Setting 
Surgery will be performed at an academic medical center.  All follow up care will be 
performed at the urology outpatient clinic. 
 
Subject selection criteria 
 Inclusion Criteria 
Ureteroscopy performed for renal stones 
Age over 18 years  
Two kidneys 
 
Exclusion Criteria 
Solitary Kidney 
Poor kidney function (GFR<30) 
Allergy to either Ibuprofen or Norco 
Pelvic Kidney 
 Sample Size 
100 Patients with the plan to enroll 50 patients in each group.   
 
Interventions and Interactions  
All subjects enrolled in the study will be randomized to either narcotic/opioid or non-opioid 
management of postoperative pain after their stones treatment. The date of treatment will be 
decided between the subject and the treating surgeon.  All treatments will be performed using the 
standard of care and will be performed in the same fashion as procedures for patients not 
enrolled in the study. There is no modification of the techniques used to remove the stones.   

Protocol version: 2 
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Post operatively, we plan to discharge all subjects home from the recovery unit with their 
designated coated pain medication supply for 7 days as well as usual scripts for alpha blockers 
and anti-muscarinic medication usually dispensed for LUTS.  All subjects will be seen one week 
after surgery for follow up, collection of the remaining study medication, review of ED visits and 
pain medication refills, questioner filling and stent removal. 
 
Outcome Measure(s) 
The primary outcome will be the amount of pain medication used in each treatment arm and the 
need for additional pain medication and refills. Secondary outcomes will be needed ED visits, 
phone calls to clinic and symptoms evaluation using a validated questioner filled during their 
clinic visit.   
 
Analytical Plan 
Results will be analyzed initially using descriptive statistics.  Comparison between groups will 
be done using chi square tests for proportions, and t-tests or ANOVA procedures for continuous 
variables.  Regression analysis will be performed to identify independent outcome predictors.  
Other inferential statistical analysis will be conducted as appropriate. 
 
Human Subjects Protection 
 
Subject Recruitment Methods 
There will be no active recruitment of subjects.  All subjects will be identified based on referrals 
to the urology outpatient clinic.  All patients with renal stones appropriate for a ureteroscopy will 
be eligible for the study.   
 
Subject confidentially will be maintained by keeping all physical consent forms in a locked 
drawer in a locked office in Wattlington Hall.  All electronic data will be maintained on a 
password secured computer in the hospital.  This study does not require the transmission of an 
PHI to any entity outside the study team. No record of the study will be placed in the medical 
record so nobody outside the study team will know that the patient will be enrolled in the study.  
 
All data and documents related to the study will be destroyed 36 months after completion of the 
study. 
 
Informed Consent 
 
Signed informed consent will be obtained from each subject.  Consent will be obtained by a member of 
the study team.  Consent will be obtained during the initial clinic visit at the urology outpatient clinic.  
 
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to assess study outcomes, 
minimizing to the fullest extent possible the collection of any information that could directly identify 
subjects, and maintaining all study information in a secure manner.  To help ensure subject privacy and 
confidentiality, only a unique study identifier will appear on the data collection form.  Any collected 
patient identifying information corresponding to the unique study identifier will be maintained on a 
linkage file, store separately from the data.  The linkage file will be kept secure, with access limited to 

Protocol version: 2 
Updated 9-9-19 
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designated study personnel.  Following data collection subject identifying information will be destroyed 
after 36 months, consistent with data validation and study design, producing an anonymous analytical 
data set.  Data access will be limited to study staff.  Data and records will be kept locked and secured, 
with any computer data password protected.  No reference to any individual participant will appear in 
reports, presentations, or publications that may arise from the study. 
 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants.  The principal investigator will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will 
be promptly reported by the principal investigator or designated member of the research team to the IRB 
and sponsor or appropriate government agency if appropriate. 
 
 
 
 
References 
1. Finney RP. Experience with new double J ureteral catheter stent. J Urol. 1978 Dec;120(6):678-
681. 
2. Assimos D, et al. Surgical management of stones: American urological 
association/endourological society guideline. J Urol. 2016;196(4):1161–9 
3. Joshi HB, Okeke A, Newns N, Keeley FX Jr, Timoney AG. Characterization of urinary 
symptoms in patients with ureteral stents. Urology. 2002 Apr;59(4):511-516. 
4. Mosli HA, Farsi HMA, al-Zimaity MF, Saleh TR, al-Zamzami MM. Vesicoureteral reflux in 
patients with double pigtail stents. J Urol. 1991;146(4):966–969. 
5. Chew BH, Knudsen BE, Nott L, Pautler SE, Razvi H, Amann J, et al. Pilot study of ureteral 
movement in stented patients: first step in understanding dynamic ureteral anatomy to improve 
stent comfort. J Endourol. 2007;21(9):1069–75. 
6. Al-Kandari AM, et al. Effects of proximal and distal ends of double-J ureteral stent position on 
postprocedural symptoms and quality of life: a randomized clinical trial. J Endourol. 2007;21(7): 
698–702. 
7. Joshi HB, et al. Ureteral stent symptom questionnaire: development and validation of a 
multidimensional quality of life measure. J Urol. 2003;169(3):1060–1064. 
8. Theisen K, Jacobs B, Macleod L, Davies B. The United States opioid epidemic: a review of the 
surgeon's contribution to it and health policy initiatives.  BJU Int. 2018 Nov;122(5):754-759. 
9. Large T, Heiman J, Ross A, Anderson B, Krambeck A. Initial Experience with Narcotic-Free 
Ureteroscopy: A Feasibility Analysis. J Endourol. 2018 Oct;32(10):907-911. 
10. Sobel DW, Cisu T, Barclay T, Pham A, Callas P, Sternberg K. A Retrospective Review 
Demonstrating the Feasibility of Discharging Patients Without Opioids After Ureteroscopy and 
Ureteral Stent Placement. J Endourol. 2018 Nov;32(11):1044-1049. 
 
 
Appendix 
1. Consent form  
2. Ureteral stent symptoms questionnaire (USSQ)