Metabolic Potentiation of Aminoglycosides: a Novel Antimicrobial Strategy to Prevent Urinary Tract Infections (UROPOT TRIAL).

Status: Recruiting
Location: See location...
Intervention Type: Drug, Combination product
Study Type: Interventional
Study Phase: Early Phase 1
SUMMARY

Urinary tract hardware such as pig-tail catheters are are frequently used for management of urolithiasis or other obstructive pathologies. They are readily colonized by urogenital flora leading to asymptomatic bacteriuria. While asymptomatic bacteriuria is not per se a problem for patients, it may lead to severe infections in the context of hardware manipulation leading to mucosal damage (e.g. catheter exchanges or stone extraction). Such interventions therefore warrant an antibiotic prophylaxis. However, bacteria rapidly form biofilms on hardware; aside of fluoroquinolones, antibiotics have limited anti-biofilm activity. Furthermore, the widespread use of antibiotics has lead to resistant strains. Hence, novel antimicrobial strategies are needed. Recently, metabolism-based potentiation of aminoglycoside has shown high antimicrobial activity against persistent forms of bacteria such as biofilms in the context of murine catheter-associated urinary tract infections. Because of the highly favorable pharmacodynamic profile of aminoglycoside in the urinary tract and the metabolic potentiation, aminoglycosides can be reduced to levels with minimal toxicity. UROPOT aims to compare the efficacy of potentiated aminoglycoside to standard of care for (i) prophylaxis of asymptomatic bacteriuria during urinary hardware manipulations with mucosal trauma (Pig-tail catheter exchange, stone surgery with prior in-dwelling catheter, etc.) and (ii) sustained microbiological eradication through antibiofilm activity. UROPOT will compare the rate of post-interventional urinary tract infections (primary outcome). It will also assess safety and eradication potency (microbiological outcome).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Written informed consent

• Adults (≥18 years)

• Ureteral stent in situ

• Patients scheduled for endourological ureteral manipulations (e.g. endourological stone surgery, ureteral stent exchange)

• Asymptomatic bacteriuria with strains of E. coli and/or K. pneumoniae sensitive to Ceftriaxone and Amikacin/Aminoglycosides.

Locations
Other Locations
Switzerland
CHUV
RECRUITING
Lausanne
Contact Information
Primary
Sylvain Meylan, MD-PhD
sylvain.meylan@chuv.ch
+41795569418
Backup
Beat Roth, Prof.
beat.roth@chuv.ch
+41213142981
Time Frame
Start Date: 2024-01-16
Estimated Completion Date: 2026-04-15
Participants
Target number of participants: 90
Treatments
Active_comparator: Ceftriaxone (CRO)
Ceftriaxone infusion. Ceftriaxone is a beta-lactam antibiotic that is the standard-of-care antibiotic for prophylaxis of asymptomatic bacteriuria in Switzerland. The choice of 2000 mg delivered intravenously reflects the general practice.
Active_comparator: Aminoglycoside (AMK)
Amikacin infusion Amikacin is an aminoglycoside routinely used in Australia (e.g. amikacin, gentamicin) as the standard of care for antibiotic prophylaxis for endourological treatments. It is also used globally for fever in neutropenia in hematological patients. Due to their relatively limited use, aminoglycosides have low resistance rates amongst Enterobacteriaceae. A single dose of 1000mg will be used intravenously
Experimental: AminoglycosideLD + Mannitol (AMK1/2 + MAN)
Amikacin + Mannitol combination The addition of Mannitol enhances bactericidal effect of amikacin in E.coli and K.pneumoniae in animal models and allows for a decrease of amikacin dosing. A single dose of 500mg (low dose or LD - decrease by 50%) systemic amikacin will be used intravenously in combination with 5 grams mannitol delivered intravenously.
Sponsors
Collaborators: Ecole Polytechnique Fédérale de Lausanne, Insel Gruppe AG, University Hospital Bern
Leads: Centre Hospitalier Universitaire Vaudois

This content was sourced from clinicaltrials.gov