Clinical trial NCT04112160
Conditions: Pain Urinary Stone Urinary Calculi
Keywords: stent removal, pain, kidney stones
Sponsor: University of Texas Southwestern Medical Center
Start date: 2018-06-28; Completion date: 2019-08-30
Enrollment: 125 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a prospective randomized double-blind controlled trial assessing the benefits of intramuscular ketorolac before or immediately after office ureteral stent removal.

Detailed description:
Patients who are undergoing cystoscopy with ureteral stent removal at the University of Texas Southwestern Medical Center and have no contraindications to receiving ketorolac will be eligible. Patients will be randomized to receive either a 1 mL injection of ketorolac tromethamine or 1 mL injection of normal saline (0.9%) as the control arm. Ketorolac is a member of the pyrrolo-pyrrole group of non steroid anti inflammatory drugs. The mechanism of action of ketorolac, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition. The peak analgesic effect occurs within 2-3 hours. If no contraindications exist, ketorolac can be safely given to patients of any age in the 30 mg intramuscular formulation if given as a one time dose according to the package insert.

Normal saline contains 0.9% of Sodium chloride in each mL. Like ketorolac, it is a clear solution and given that there are no major side effects of normal saline it is a good control for our study. It is packaged in a single dose vial that contains 100 mL. It is preservative free and stored at room temperature (20-25°C). Local pain at the injection site may occur, temporarily.

The investigators will specifically look at pain scores before and after stent removal as well as narcotic medication use, telephone calls and/or emergency room visits for pain. Based on the rate of renal colic from our quality improvement project and prior work, the investigators calculated the maximum number of local subjects to be consented for this study to be n=116 (see biostatistics section). The study is expected to last 6 months.

Arms: arm 1: normal saline 0.9% arm 2: 30 mg of Ketorolac
Interventions: intervention 1: Ketorolac intervention 2: normal saline
Intervention descriptions: intervention 1: IM injection of either normal saline or Ketorolac intervention 2: normal saline

Protocol documents:
Prot_SAP_ICF_000.pdf: 
 
 
 
 
 
Prospective Randomized Controlled Trial for 
Pain Relief after Office Ureteral Stent Removal 
 
Study Protocol and Statistical Analysis Plan 
NCT04112160 
06/09/2020 
 
 
 
 
 
 
 
 
 


1. Introduction and Purpose: 
Ureteral stents placed after ureteroscopy (URS) for nephrolithiasis can be extremely bothersome 
for patients in the post-operative period. Even more troubling, a subset of patients experience 
debilitating renal colic for hours after the stent is removed despite use of narcotic analgesics. The 
purpose of this study is to determine if the use of pre-emptive ketorolac will prevent or reduce 
the acute pain experienced by some patients after stent removal.  
 
2. Background: 
Nephrolithiasis is a prevalent disease in the United States increasing to nearly 9% in the last 
decade.[1] Recently, there has been increasing attention focused on improving health-related 
quality of life (HRQOL) for patients with nephrolithiasis.[2] While randomized controlled trials 
(RCTs) are limited in this area, HRQOL is diminished in patients undergoing surgical 
intervention for nephrolithiasis, especially for those in whom ureteral stents were placed.[3] 
There are a multitude of studies focusing on reducing pain while the stent is indwelling, 
including the use of alpha blockers, anticholinergics, and narcotics.[4, 5] However, acute pain 
can occur for 1-24 hours after the indwelling stent is removed, substantially reducing quality of 
life. In our own quality improvement project at UT Southwestern we attempted to quantify 
quality of life metrics after URS and found that 57% of patients (12 of 21) reported experiencing 
renal colic after stent removal at home. Two of those patients went to the emergency department 
(ED) for severe pain right after stent removal that required intravenous medications.  
 
Ketorolac is a safely and commonly used non-steroidal anti-inflammatory (NSAID) medication 
for acute renal colic.[6, 7] Ketorolac has also been uniquely formulated into intravesical 
instillations and indwelling ureteral stents for pain relief in the the post-operative period after 
URS. An RCT evaluated a ketorolac-loaded ureteral stent which helped reduce pain medication 
use in younger male patients between post-operative days 2-4.[8] No difference in pain scores 
after day 4 or in the number of interventions for pain were noted. In another study evaluating 
intravesical ketorolac instillation after stent placement showed benefit in the very early post-
operative period (1 hour).[9] As ureteral stents are usually left indwelling for at least 1 week, an 
additional measure aimed at pain prevention is likely necessary after the acute benefits of 
ketorolac have worn off.  
 
We propose an intervention by which ketorolac is administered intramuscularly immediately 
prior to office stent removal, effectively antagonizing pain receptors so that patients feel relief 
during and for at least 6 hours after removal, a time period that we have determined from our 
quality improvement project as the most likely time frame  for patients to return to the ED. 
Furthermore, in regard to the recent focus of reducing opioid use, ketorolac injection will likely 
decrease or obviate the need for any narcotics after stent removal.   
 
3. Concise Summary of Project: 
This is a prospective randomized double-blind controlled trial assessing the benefits of 
intramuscular ketorolac before office ureteral stent removal. Patients who are undergoing 
cystoscopy with ureteral stent removal at the University of Texas Southwestern Medical Center 
and have no contraindications to receiving ketorolac will be eligible. Patients will be randomized 
to receive either a 1 mL injection of ketorolac tromethamine or 1 mL injection of normal saline 
(0.9%) as the control arm. Ketorolac is a member of the pyrrolo-pyrrole group of NSAIDs. The 


mechanism of action of ketorolac, like that of other NSAIDs, is not completely understood but 
may be related to prostaglandin synthetase inhibition. The peak analgesic effect occurs within 2-
3 hours. If no contraindications exist, ketorolac can be safely given to patients of any age in the 
30 mg intramuscular formulation if given as a one time dose according to the package insert 
(http://www.sagentpharma.com/wp-content/uploads/2016/01/Ketorolac_-PI.pdf). It is supplied in 
a single-dose vial which contains either 30 mg per mL or 60 mg per 2 mL. Packages come with 
25 vials per carton which costs around $22 from the Aston pharmacy. It is recommended to store 
ketorolac at room temperature (20-25°C) and to protect from light until time of use. Unused 
portions should be discarded.  
 
Normal saline contains 0.9% of NaCl in each mL 
(https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2a98378-9678-4738-9670-
fc7a215c0606) . Like ketorolac, it is a clear solution and given that there are no major side 
effects of normal saline it is a good control for our study. It is packaged in a single dose vial that 
contains 100 mL. It is preservative free and stored at room temperature (20-25°C). Local pain at 
the injection site may occur, temporarily.  
 
 
4. Randomization: 
After meeting inclusion procedure, patients were randomized into either the control or treatment 
arm. A computer-based random sequence generator was used for randomization. The allocation 
sequence was kept by a research nurse and concealed from the investigators and providers 
involved in the study. Statistical analysis was performed by a blinded investigator. Allocation 
was revealed after conclusion of the study. 
 
5. Inclusion and Exclusion Criteria: 
Adult patients between 18 and 80 years of age who have undergone ureteroscopy for 
nephrolithiasis by 2 fellowship trained surgeons (JA, MP) and placement of indwelling double-J 
ureteral stent(s) with or without tether at a single institution were included. Patients were 
required to have their stent removed in our ambulatory urology clinic. Patients were excluded if 
they had an absolute or relative contraindications to ketorolac. Patients with an eGFR <50, any 
active or history of peptic ulcer disease or gastrointestinal bleeding, bleeding disorder, suspected 
of confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, 
concurrent use of warfarin or heparin, allergic reaction to NSAIDs, concurrent use of aspiring or 
other NSAIDs, pregnancy, recent myocardial infarction were excluded. If patients had evidence 
of acute renal failure at the time of stent placement, a basic metabolic profile was be checked 
prior to the stent removal to ensure eligibility and safety for the study. 
 
6. Medication Administration and Procedure: 
Patients randomized to the treatment arm were given 30mg in 1mL intramuscular injection of 
ketorolac tromethamine immediately prior to removal of the ureteral stent in the ambulatory 
urology setting. Patients in the control arm were given a 1 mL intramuscular injection of 0.9% 
normal saline prior to stent removal. Medication to be injected was drawn up on the morning of 
stent removal by the research nurse in charge of the randomization sequence. Injections were 
performed by a different qualified registered nurse who was blinded to the medication.  Stents 
were removed by the nurse if they were on a tether or via cystoscopy with the use of viscous 


lidocaine instilled into the urethra. Patients in both arms were extensively counseled on 
expectations and symptoms to look for after stent removal. 
 
7. Data Collection: 
Patient demographical and surgical information was collected prospectively by a blinded 
investigator. Patients were then be contacted via telephone at 24 hours and 7 days following stent 
removal. Visual analog pain (VAS) scale, renal colic symptoms, need for narcotic medications, 
and instance of an unplanned pain-related clinical encounter, surgical interventions, and missed 
work were recorded.  Unplanned pain-related clinical encounters were either ED visits or an 
unplanned ambulatory encounter with the urology clinic. 
 
8. Statistical Analysis: 
A student’s t-test and Mann–Whitney U test was for means and medians, respectively. The chi-
square test was performed for categorical variables if each category was greater than 20% of 
total. A Fisher’s Exact Test was used for categorical variables if a category was less than 20% of 
total. All tests were run as a two-tailed tests and deemed significant if p ≤ 0.05. 
 
 
 
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