Objective: The main objective is to demonstrate superiority of the intravesical overnight instillation of gentamicin versus oral antibiotic prophylaxis in reducing the number of recurrences of UTI and extending the time-interval to a next UTI, in…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Urinary tract signs and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: The primary end point is defined as the number
of UTI per patient after initiation of the study during the first 6 months
(prophylactic treatment) and during 12 months (total follow up).
Secondary outcome
Secondary endpoints include the time to first, second and third UTI after start
of intravesical gentamicin or oral antimicrobial prophylaxis, the
microbiological cure rate in males with chronic bacterial prostatitis, the need
for oral and/or intravenous antibiotic-courses for UTI in hospital/day-care
setting during the year of the study, patients* satisfaction with the treatment
and the development of antimicrobial resistance of uropathogens and commensal
flora.
Background summary
Rationale: Management of patients with recurrent urinary tract infections (UTI)
is challenging, even more so in the era of rising antimicrobial resistance.
Multidrug-resistance is currently leading to an increased need for intravenous
treatment of UTIs with reserve antibiotics and subsequent hospitalizations.
Prophylaxis with low dose oral antibiotics, as recommended by current
guidelines, is often limited by multidrug-resistance of uropathogens, and if
possible may even further extent the development of resistance. In such
patients with recurrent UTI due to multi-drug resistant uropathogens,
intravesical gentamicin installation is a potential valuable treatment option
for either suppression or prevention of UTI. Locally administered
aminoglycosides bypass systemic toxicity and development of antimicrobial
resistance is unlikely because of high urinary levels and lack of antibiotic
pressure on commensal gut flora.
Study objective
Objective: The main objective is to demonstrate superiority of the intravesical
overnight instillation of gentamicin versus oral antibiotic prophylaxis in
reducing the number of recurrences of UTI and extending the time-interval to a
next UTI, in adults with recurrent UTIs. Secondary objectives include
assessment of the acceptability and the safety of intravesical installation of
gentamicin and the influence on development of antibiotic resistance of
uropathogens.
Study design
Study design: Randomized, controlled, open-label, intervention study.
Intervention
Intervention: The intervention group receives intravesical installations of
gentamicin during a period of 24 weeks (once daily for 2 weeks, every other day
for 10 weeks, twice weekly for 12 weeks). The control group receives low dose
oral antibiotic prophylaxis based on prior susceptibility pattern of isolated
uropathogens and patient characteristics, reflecting current standard care.
Study burden and risks
Nature and extent of the burden and risks associated with participation and
benefit:
In this therapeutical trial treatment with intravesical gentamicin will be
compared to current standard of care. Subjects participating in the study will
receive a baseline evaluation including standard diagnostic procedures in
patients with recurrent UTI. Follow up consists of 7 outpatient clinic visits,
7 blood samples, 6 urine cultures, and 2 cultures of perineal/vaginal flora.
Symptoms, treatment details, side effects and quality of life will be evaluated
by standardized questionnaires obtained on each follow up visit.
By direct instillation of gentamicin in the bladder, high concentrations can be
reached without concerns on systemic side effects. Systemic uptake of
gentamicin will be monitored during treatment; in case of detectable gentamicin
serum levels, intravesical treatment might be discontinued as judged by the
principal investigators.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1. Competent patient aged 18 or above.
2. A history of recurrent cystitis, defined as:
a. females: at least 2 episodes of UTI in the last 6 months or 3 in the last 12 months
b. males: at least 2 episodes of UTI in the last 12 months (including recurrent cystitis likely due to chronic bacterial prostatitis).
3. At least one episode of these infections is documented by urine culture with the isolation of *10^3 CFU/mL of an identified MDR pathogen. Multidrug resistance is defined as acquired non-susceptibility to at least one agent in three or more antimicrobial classes.
4. All other episodes at least by one urinary symptom* and positive urinary nitrate test or leukocyturia (as depicted by positive leukocyte esterase test or microscopy).
5. No clinical symptoms of UTI at enrolment.
Exclusion criteria
1. Urinary culture in prior 6 months tested positive for high-level gentamicin resistant enterobacteriaceae or enterococci (MIC >128 mg/L).
2. Abnormalities of the upper urinary tract, including presence of urinary stones.
3. Patients with a permanent urinary catheter.
4. Complete urinary incontinence.
5. Patients with stage 5 chronic kidney disease (GFR <15 ml/min).
6. Patients with known hypersensitivity to gentamicin.
7. Pregnancy or lactation.
8. Inability to provide informed consent.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002995-42-NL |
| CCMO | NL46991.058.13 |
| OMON | NL-OMON23211 |