Intra-nasal Ketorolac for Acute Ureteral Stent-associated Pain Following Ureteroscopy for Stone Disease

Post Operative Pain Clinical Trial

Official title:

Intra-nasal Ketorolac Versus Oral Diclofenac for Acute Ureteral Stent-associated Pain Following Ureteroscopy for Stone Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06158620
• Other study ID #: STU-2023-0775
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Brett Johnson, MD
• Phone: 214/645-8765
• Email: brett.johnson[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Objective: To improve quality-of-life and health care delivery to patients receiving ureteral stents.

Specific Aims: Evaluate the feasibility, practicality, and qualitative outcomes of utilizing intra-nasal ketorolac in patients with indwelling ureteral stents (Phase I), followed by a randomized trial comparing two non-steroidal anti-inflammatory drugs, intra-nasal Ketorolac versus oral Diclofenac.

Hypotheses: Due to its favorable pharmacokinetics in relieving acute pain, investigators expect improved pain scores and a lower rate of unplanned clinical encounters in patients receiving intra-nasal ketorolac compared to those taking oral diclofenac following ureteroscopic surgery for urolithiasis.

Study Rationale: Following ureteroscopic management of urolithiasis, patient with indwelling ureter stents have higher levels of discomfort compared to those without a ureter stent. Prior studies showed that intramuscular Ketorolac at time of ureter stent removal decreased the incidence of unplanned clinical encounters. Furthermore, onset of analgesic effect by intra-nasal ketorolac is faster than its oral form, and similar its intramuscular and intravenous counterparts.

Description:

Urinary stone disease (USD) leads to pain, diminished quality of life, missed work and school, chronic kidney disease, and renal failure.1-5 The prevalence of kidney stone disease in adults has risen to almost 9% as of 2010 in the United States (US). The 5-year recurrence rate without treatment is 53%.6,7 Increasing utilization of a ureteroscopic approach to treat urolithiasis has led to an increased proportion of stone patients undergoing ureteral stent placement.

In the US, approximately 90% of patients receive a ureteral stent following ureteroscopy. Some patients that undergo ureteral stent placement experience significant and debilitating symptoms of urinary urgency, frequency, suprapubic and flank pain, and incontinence. Treatment of these symptoms has historically relied heavily on opioid pain medications. However, recent emphasis on risk associated with opioid medications has reduced their use, and paved the way for alternative approaches. As such, non-steroidal anti-inflammatory drugs (NSAIDs) have become an integral part of multimodal techniques at mitigating post operative pain and associated ureter stent discomfort.

Ketorolac, an NSAID, can be used in the management of acute pain related to ureteral obstruction, renal colic, and indwelling ureter stent. There are four available formulations of ketorolac: oral, intra-muscular (IM), intra-nasal (IN), and intravenous (IV). Non-oral formulations are known to have faster onset of action and an earlier peak analgesic effect.8 As opposed to injectable (IM or IV) ketorolac that needs to be administered by a clinical provider, IN ketorolac may conveniently be self-administered.9 Furthermore, the favorable pharmacokinetics of IN ketorolac allow for its significant efficacy in providing timely pain relief without the need of opioid medications. However, one of the significant barriers of intra-nasal ketorolac is the cost. An intra-nasal course can cause upwards of $1500 compared to $20 of oral ketorolac.

Ketorolac prevents unplanned renal colic-related clinical encounters post stent removal.10 Study team recently published the study team's results from a randomized trial comparing intramuscular injection of ketorolac to placebo at the time ureteral stent removal reduced the incidence of unplanned clinic returns or emergency room visits. While this trial was aimed at the small number of patients that develop severe ureteral colic following stent removal, investigators feel ketorolac's strong anti-inflammatory properties can be leveraged to mitigate acute indwelling ureteral stent symptoms.

While it is not feasible to treat every stent patient empirically with IN ketorolac, there may be an identifiable subset of patients that may benefit from this formulation. Its favorable pharmacokinetics allow for its significant efficacy in providing timely pain relief without the need of opioid medications. This makes IN ketorolac an intriguing option that may decrease unplanned clinical encounters related to indwelling ureter stent discomfort. Especially when the cost of a post-operative emergency room visits which can include laboratory testing, computed tomography, IV medication and possible admission can dwarf the cost of IN ketorolac.

Furthermore, a recent qualitative analysis published by Harper et al in the in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS) study reveal a highly variable patient experience with stents.11 For some, the negative experience of the stent can be life altering. Therefore, there is a critical need to improve the pain and quality of life of those requiring ureteral stenting. Ideally, this can be done in a directed way to offer more relief to those patients most at risk for severe symptoms.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• =18 years old

• English-speaking

• Candidate for unilateral ureteroscopy for treatment of urolithiasis

• Surgical plan includes placement of a ureteral stent

Exclusion Criteria:

• Pregnant/nursing, prisoners, cognitively impaired

• Solitary kidney

• Stone in transplant kidney

• Anatomic abnormalities (i.e., ureteral stricture, infundibular stenosis, uretero-pelvic junction obstruction, horseshoe kidney, duplicated system)

• History of ureteral reconstruction

• History of nephrocalcinosis, medullary sponge kidney, cystinuria

• Immobility or relative immobility

• Planned staged ureteroscopy

• History of ureteral stent complication or poor tolerance or a ureteral stent

• Urinary tract infection or sepsis

• Current anticoagulation use (81 mg Aspirin permissible)

• NSAID contraindication (acute renal failure or chronic kidney disease, bleeding disorders, allergic reaction to NSAIDs, ulcer disease, auto-immune disease)

Related Conditions & MeSH terms

• Calculi
• Pain, Postoperative
• Post Operative Pain
• Stent Complication
• Ureter Calculi
• Urolithiasis

Intervention

Drug:
• intra-nasal ketorolac
Experimental group receiving intra-nasal ketorolac for management of post-operative pain following ureteroscopy for kidney stone, and associated ureter stent discomfort.
• oral diclofenac
Control group to receive oral diclofenac, which is a comparable medication to intra-nasal ketorolac.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	assertio Therapeutics, Inc

Country where clinical trial is conducted

United States, 

References & Publications (12)

Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Morgan C, Samuel S, Klarenbach SW, Curhan GC, Tonelli M; Alberta Kidney Disease Network. Kidney stones and kidney function loss: a cohort study. BMJ. 2012 Aug 29;345:e5287. doi: 10.1136/bmj.e5287. — View Citation

Allam CL, Aden JK, Reed AM. The Role of Routine Ureteral Stenting Following Uncomplicated Ureteroscopic Treatment for Upper Ureteral and Renal Stones: A Randomized Control Trial. J Endourol. 2023 Mar;37(3):257-263. doi: 10.1089/end.2022.0386. Epub 2023 Jan 9. — View Citation

Bensalah K, Tuncel A, Gupta A, Raman JD, Pearle MS, Lotan Y. Determinants of quality of life for patients with kidney stones. J Urol. 2008 Jun;179(6):2238-43; discussion 2243. doi: 10.1016/j.juro.2008.01.116. Epub 2008 Apr 18. — View Citation

Harper JD, Desai AC, Antonelli JA, Tasian GE, Ziemba JB, Al-Khalidi HR, Lai HH, Maalouf NM, Reese PP, Wessells HB, Kirkali Z, Scales CD Jr; NIDDK Urinary Stone Disease Research Network (USDRN). Quality of life impact and recovery after ureteroscopy and stent insertion: insights from daily surveys in STENTS. BMC Urol. 2022 Apr 6;22(1):53. doi: 10.1186/s12894-022-01004-9. — View Citation

Johnson BA, Sorokin I, Antonelli J, Pearle M. Efficacy of Intramuscular Ketorolac for Preventing Renal Colic Post Stent Removal: Randomized Controlled Trial. J Urol. 2022 Sep;208(3):650-657. doi: 10.1097/JU.0000000000002750. Epub 2022 Jun 2. — View Citation

Ljunghall S, Danielson BG. A prospective study of renal stone recurrences. Br J Urol. 1984 Apr;56(2):122-4. doi: 10.1111/j.1464-410x.1984.tb05346.x. — View Citation

Pearle MS. Medical therapy for urinary stone passage. Lancet. 2006 Sep 30;368(9542):1138-9. doi: 10.1016/S0140-6736(06)69452-X. No abstract available. — View Citation

Saigal CS, Joyce G, Timilsina AR; Urologic Diseases in America Project. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int. 2005 Oct;68(4):1808-14. doi: 10.1111/j.1523-1755.2005.00599.x. — View Citation

Shoag J, Halpern J, Goldfarb DS, Eisner BH. Risk of chronic and end stage kidney disease in patients with nephrolithiasis. J Urol. 2014 Nov;192(5):1440-5. doi: 10.1016/j.juro.2014.05.117. Epub 2014 Jun 11. — View Citation

Singla N, Singla S, Minkowitz HS, Moodie J, Brown C. Intranasal ketorolac for acute postoperative pain. Curr Med Res Opin. 2010 Aug;26(8):1915-23. doi: 10.1185/03007995.2010.495564. Erratum In: Curr Med Res Opin. 2012 Jun;28(6):1052. — View Citation

Uribarri J, Oh MS, Carroll HJ. The first kidney stone. Ann Intern Med. 1989 Dec 15;111(12):1006-9. doi: 10.7326/0003-4819-111-12-1006. — View Citation

Vadivelu N, Gowda AM, Urman RD, Jolly S, Kodumudi V, Maria M, Taylor R Jr, Pergolizzi JV Jr. Ketorolac tromethamine - routes and clinical implications. Pain Pract. 2015 Feb;15(2):175-93. doi: 10.1111/papr.12198. Epub 2014 Apr 16. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pain scores as measured by USSQ Pain Survey	Associated pain burden will be measured using standardized Ureteral Stent Symptom Questionnaire (USSQ) Pain Survey. Possible scores range from 0-10, where lower scores indicate better outcome.	Baseline (before surgery in the pre-operative setting -Day 0), the day of ureter stent removal (Post-operative day 5 through 10)
Primary	Change in pain scores as measured by PROMIS questionnaire	Associated pain burden will be measured using standardized Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity and Interference questionnaire. Possible scores range from 0-10, where lower scores indicate better outcome.	Baseline (before surgery in the pre-operative setting -Day 0), the day of ureter stent removal (Post-operative day 5 through 10)
Primary	Change in pain scores as measured by Likert Scale Questionnaire	Associated pain burden will be measured using standardized Likert Scale Questionnaire. Possible scores range from 0-10, where lower scores indicate better outcome.; For those patients in the SPIRIX arm, they will be asked to complete the Likert Scale Questionnaire approximately 30 minutes after taking each SPIRIX dose.	Baseline (before surgery in the pre-operative setting -Day 0), the day of ureter stent removal (Post-operative day 5 through 10)
Secondary	Number of unplanned clinical encounters	number of clinical encounters (i.e. telephone calls, MyChart messages, emergency room visits, hospital readmissions) related to ureter stent discomfort will be counted.	Post-operative setting -the day of ureter stent removal (Post-operative day 5 through 10)