Use of Antibiotic Based Irrigation for Ureteroscopic Treatment of Urolithiasis

The purpose of the study is to investigate whether the use of gentamicin-based irrigation fluid during ureteroscopy decreases the risk of UTIs and other post-operative infections after surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Urinary Tract Infections
• Intervention / Treatment: Drug: Gentamicin; Other: Placebo

Detailed Description

The primary objective of this study is to determine whether the utilization of gentamicin-based irrigation fluid during ureteroscopy decreases the rate of 30-day post-operative symptomatic urinary tract infections in patients at higher risk of urinary tract infection undergoing stone surgery for urolithiasis.

The secondary objectives of this study are to determine whether the utilization of gentamicin-based irrigation fluid during ureteroscopy affects the 30-day post-operative rates of patient-initiated telephone calls, readmission rates, urosepsis rates based on SIRS criteria, and overall post-operative oral/intravenous antibiotic administration.

In this prospective study, 120 mg of gentamicin prepared in 3 liters of normal saline will be used as irrigation during ureteroscopic surgery for urolithiasis. At this concentration, 40 μg/mL, the MBC would be achieved for pathogenic urogenital bacteria. Due to the concerns of nephrotoxicity and ototoxicity at higher doses of gentamicin, in the unlikely event of complete pyelo-venous backflow, the intravenous circulation of 120 mg of gentamicin would be less than the surgical prophylaxis intravenous dosing for patients weighing more than 60 kg. For the single intravenous dose for surgical prophylaxis, post-operative monitoring of renal function, and gentamicin peak and trough levels are not routinely obtained.

• Study Type: Interventional
• Enrollment (Estimated): 412
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Piruz Motamedinia, M.D.; Phone Number: 203-785-2815; Email: piruz.motamedinia@yale.edu
• Study Contact Backup: Name: Ankur Choksi, M.D.; Email: ankur.choksi@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Health
      • Contact: Piruz Motamedinia, M.D.; Email: piruz.motamedinia@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Diagnosed with urolithiasis (obstructing ureteral stone, large non-obstructing renal stones) warranting surgical intervention in line with American Urological Association guidelines for urolithiasis
• At a higher risk for infectious complications following ureteroscopy based on a history of atleast one of the below:
• 3 more urinary tract infections over 12 month period not on suppressive antibiotic therapy
• Prior infectious complication following ureteroscopy
• Placement of ureteral stent in the setting of obstructing ureteral stone with concern for superimposed urinary tract infection
• Positive pre-operative urine culture treated with culture-appropriate antimicrobial therapy
• Planned for cystoscopy, ureteroscopy with possible laser lithotripsy, and ureteral stent placement
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of gentamicin administration. Female patients of reproductive potential will have pregnancy screen prior to surgery per standard operating room protocol.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

Exclusion Criteria:

• Estimated Glomerular Filtration Rate less than 60 mL/min
• History of sensorineural hearing loss, vertigo, idiopathic dizziness
• Active pregnancy or currently lactating
• Known allergic reactions to components of gentamicin
• Administration of intravenous gentamicin as part of surgical antibiotic prophylaxis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gentamicin-Based Irrigation; This group will receive 120 mg of Gentamicin in 3 L NaCl as irrigation fluid during ureteroscopy	Drug: Gentamicin; Participants will be given 120 mg of gentamicin infused in 3 L NaCl used in irrigation for ureteroscopy
Placebo Comparator: 3 L NaCl Irrigation; This group will receive the typical NaCl irrigation used during ureteroscopy	Other: Placebo; 3 L of NaCl irrigation typically used for ureteroscopy surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic urinary tract infection	Development of a symptomatic urinary tract infection after surgery	Within 30 days of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urosepsis	Development of urosepsis after URS based on SIRS criteria	Within 30 days of surgery
Re-admission to hospital	Re-admission to hospital after surgery for any reason	Within 30 days of surgery
Patient self-reported symptoms	Self-reported symptoms after the operation of the following: new hearing loss, vertigo and dizziness	within 30 days of surgery

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Piruz Motamedinia, M.D., Yale School of Medicine, Department of Urology

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ureteroscopy; UTI; Gentamicin
• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Pathological Conditions, Anatomical; Calculi; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Tract Infections; Urinary Calculi; Urolithiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Gentamicins
• Other Study ID Numbers: 2000035721; 000 (Other Identifier: CTGTY)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes