Use of Antibiotic Based Irrigation for Ureteroscopic Treatment of Urolithiasis

• ClinicalTrials.gov Identifier: NCT06007352
• Recruitment Status: Not yet recruiting
• First Posted: August 23, 2023
• Last Update Posted: March 26, 2024
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Urinary Tract Infections; Sepsis	Drug: Gentamicin; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 412 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: phase II, parallel randomized control trial with 1:1 allocation
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Use of Antibiotic Based Irrigation for Ureteroscopic Treatment of Urolithiasis
• Estimated Study Start Date: May 2024
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: June 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Symptomatic urinary tract infection [ Time Frame: Within 30 days of surgery ]
   Development of a symptomatic urinary tract infection after surgery

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Piruz Motamedinia, M.D.; 203-785-2815; piruz.motamedinia@yale.edu

Contact: Ankur Choksi, M.D.; ankur.choksi@yale.edu

Locations

United States, Connecticut

Yale New Haven Health

New Haven, Connecticut, United States, 06510

Contact: Piruz Motamedinia, M.D. piruz.motamedinia@yale.edu

Sponsors and Collaborators

Yale University

Investigators

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

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT06007352
• Other Study ID Numbers: 2000035721; 000 ( Other Identifier: CTGTY )
• First Posted: August 23, 2023
• Last Update Posted: March 26, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Yale University:

UTI; Gentamicin; Ureteroscopy

Additional relevant MeSH terms:

Urinary Tract Infections; Urolithiasis; Urinary Calculi; Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Gentamicins; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action