- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05761405
Potentiated Aminoglycosides in Postoperative Urinary Tract Infection Prophylaxis (UROPOT)
Metabolic Potentiation of Aminoglycosides: a Novel Antimicrobial Strategy to Prevent Urinary Tract Infections (UROPOT TRIAL).
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).
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Sylvain Meylan, MD-PhD
- Phone Number: +41795569418
- Email: sylvain.meylan@chuv.ch
Study Contact Backup
- Name: Beat Roth, Prof.
- Phone Number: +41213142981
- Email: beat.roth@chuv.ch
Study Locations
-
-
-
Lausanne, Switzerland, 1011
- Recruiting
- CHUV
-
Contact:
- Sylvain Meylan, MD-PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Allergy to one of the study drugs Beta-lactams, aminoglycosides or mannitol
- Pregnant and lactating women
- Glomerular filtration rate (CKD-EPI eGFR) < 50ml/min / 1,73m2
- Hearing impairment
- Myasthenia gravis or other forms of myoneural disorders
- Congestive heart failure, Pulmonary edema
- Intracranial hemorrhage, blood-brain barrier compromise
- Previous (within 3 months prior to randomization) or concomitant participation in another interventional clinical trial
- Antibiotic treatment within 14 days prior to randomization
- Mixed cultures of E. coli and/or K. pneumonia with other bacteria
- Inability to understand and follow the protocol
- Inability to give informed consent
- BMI<20 or >30
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Preselected patients with ureteral stents in situ who are scheduled to undergo endourological ureteral stent manipulation will have routine urine cultures prior to intervention. Procedures: Consented patients will be randomized for the type of antibiotic prophylaxis according to a global randomization list (i.e. CRO, AMK, AMK1/2+MAN)). Antibiotics will be delivered in a single infusion that will be administered within 30 minutes. |
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
|
Preselected patients with ureteral stents in situ who are scheduled to undergo endourological ureteral stent manipulation will have routine urine cultures prior to intervention.
|
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.
|
Preselected patients with ureteral stents in situ who are scheduled to undergo endourological ureteral stent manipulation will have routine urine cultures prior to intervention. Procedures: Consented patients will be randomized for the type of antibiotic prophylaxis according to a global randomization list (i.e. CRO, AMK, AMK1/2+MAN)). Antibiotics (± mannitol) will be delivered in a single infusion that will be administered within 30 minutes. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infection prophylaxis
Time Frame: 48 hours postoperatively
|
Incidence of postoperative infections within the initial 48 hours postoperatively.
|
48 hours postoperatively
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Combined microbiological eradication
Time Frame: 6-8 hours post infusion
|
anti-biofilm activity as determined by culture of sonicated catheter (CFU/ml) and intraoperative urine culture (CFU/ml)
|
6-8 hours post infusion
|
Sustained microbiological eradication
Time Frame: Up to 2 weeks
|
To document eradication of bacteriuria at postoperative day 2 and 14 day by urine culture (CFU/ml)
|
Up to 2 weeks
|
Surgical safety outcome
Time Frame: Day 0-14
|
Postoperative complications
|
Day 0-14
|
Pharmacokinetics outcome
Time Frame: Day 0, Day 2, Day 14
|
Measurements of maximum urine drug concentrations (Amikacin, Ceftriaxone, Mannitol)
|
Day 0, Day 2, Day 14
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: Day 0-Day 14
|
Safety and tolerability of Amikacin/Mannitol combination (serious adverse events (SAEs), pre-specified adverse events (AEs) of special interest (ototoxicity, nephrotoxicity).
|
Day 0-Day 14
|
Collaborators and Investigators
Investigators
- Principal Investigator: Sylvain Meylan, Centre Hospitalier Universitaire Vaudois
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Urologic Diseases
- Disease Attributes
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Infections
- Communicable Diseases
- Urinary Tract Infections
- Physiological Effects of Drugs
- Anti-Infective Agents
- Natriuretic Agents
- Anti-Bacterial Agents
- Diuretics, Osmotic
- Diuretics
- Mannitol
- Ceftriaxone
- Amikacin
Other Study ID Numbers
- 2022-001979
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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