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

NCT06158620 | Recruiting Phase 1 FDA Drug

• 1 other identifier: STU-2023-0775
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Post Operative Pain; Urolithiasis; Ureter Calculi; Stent Complication

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (1)

• Number of unplanned clinical encounters

  Post-operative setting -the day of ureter stent removal (Post-operative day 5 through 10)

Study Arms (2)

Sprix

EXPERIMENTAL

Phase I will consist of a single-arm open label pilot study. Prior to the initiation of a large-scale randomized trial, we propose a single-arm open label pilot study to evaluate the feasibility, practicality, and qualitative outcomes of utilizing intra-nasal ketorolac in patients with indwelling ureteral stents. We seek to enroll 20 patients for the initial pilot. Phase II will consist of a randomized trial comparing intranasal ketorolac to Diclofenac, a commonly used oral NSAID. , Diclofenac potassium. Following ureteroscopy and stent placement, patients will receive standard of care medications to mitigate post operative pain and stent discomfort, and will be randomized to receive either as needed intra-nasal ketorolac or oral diclofenac. We seek to enroll and randomize 60 patients in a 1:1 fashion. Analysis will be intention to treat.

Drug: intra-nasal ketorolac

Diclofenac

ACTIVE COMPARATOR

Phase II will consist of a randomized trial comparing intranasal ketorolac to Diclofenac, a commonly used oral NSAID. , Diclofenac potassium. Following ureteroscopy and stent placement, patients will receive standard of care medications to mitigate post operative pain and stent discomfort, and will be randomized to receive either as needed intra-nasal ketorolac or oral diclofenac. We seek to enroll and randomize 60 patients in a 1:1 fashion. Analysis will be intention to treat.

Drug: oral diclofenac

Interventions

intra-nasal ketorolac DRUG

Experimental group receiving intra-nasal ketorolac for management of post-operative pain following ureteroscopy for kidney stone, and associated ureter stent discomfort.

Also known as: Sprix

Sprix

oral diclofenac DRUG

Control group to receive oral diclofenac, which is a comparable medication to intra-nasal ketorolac.

Diclofenac

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old
• English-speaking
• Candidate for unilateral ureteroscopy for treatment of urolithiasis
• Surgical plan includes placement of a ureteral stent

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• assertio Therapeutics, Inc: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Related Publications (12)

• 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.

  PMID: 17011928 BACKGROUND

• 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.

  PMID: 18423704 BACKGROUND

• 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.

  PMID: 16164658 BACKGROUND

• 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.

  PMID: 24929140 BACKGROUND

• 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.

  PMID: 22936784 BACKGROUND

• 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.

  PMID: 6498430 BACKGROUND

• 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.

  PMID: 2688503 BACKGROUND

• 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.

  PMID: 24738596 BACKGROUND

• 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.

  PMID: 20557145 BACKGROUND

• 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.

  PMID: 35653577 BACKGROUND

• 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.

  PMID: 35387623 BACKGROUND

• 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.

  PMID: 36401514 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Urolithiasis

Interventions

Ketorolac; Diclofenac

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Brett Johnson, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brett Johnson, MD

CONTACT

214/645-8765; brett.johnson@utsouthwestern.edu

Isaac Palma-Zamora, MD

CONTACT

214/645-8765; isaac.palma-zamora@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Phase I will consist of a single-arm open label pilot study. Prior to the initiation of a large-scale randomized trial, we propose a single-arm open label pilot study to evaluate the feasibility, practicality, and qualitative outcomes of utilizing intra-nasal ketorolac in patients with indwelling ureteral stents. We seek to enroll 20 patients for the initial pilot. Phase II will consist of a randomized trial comparing intranasal ketorolac to Diclofenac, a commonly used oral NSAID. , Diclofenac potassium. Following ureteroscopy and stent placement, patients will receive standard of care medications to mitigate post operative pain and stent discomfort, and will be randomized to receive either as needed intra-nasal ketorolac or oral diclofenac. We seek to enroll and randomize 60 patients in a 1:1 fashion. Analysis will be intention to treat.

Study Record Dates

• First Submitted: November 26, 2023
• First Posted: December 6, 2023
• Study Start: March 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)