|- candidate number||18133|
|- NTR Number||NTR4646|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||16-jun-2014|
|- Secondary IDs||NL46991.058.13 P13.254|
|- Public Title||SPRING
Study of Prevention of Recurrent urinary tract infections by Intravesical iNstilment of Gentamicin|
|- Scientific Title||Prevention of recurrent urinary tract infections by multi-drug resistant bacteria, by intravesical administration of gentamicin.|
|- hypothesis||Prophylaxis with intravesical overnight instillation of gentamicin reduces the number of recurrences of UTI in patients with recurrent urinary tract infections due to multi-drug resistant bacteria, as compared to oral antibiotic prophylaxis.|
|- Healt Condition(s) or Problem(s) studied||Urinary tract infections, Multi-drug resistant bacteria, Cystitis, Prophylaxis|
|- Inclusion criteria||- Competent patient aged 18 or above. |
- 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).
- 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.
- 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).
- No clinical symptoms of UTI at enrolment.
Ad * Definitions of urinary symptoms:
- Dysuria: pain, tingling or burning sensation in the perineum during or just after urination.
- Frequency: more than usual, abnormal, frequent voiding.
- Urgency: unusual intense and sudden desire or urge to void.
- Suprapubic and/or perineal pain.
|- Exclusion criteria||- Urinary culture in prior 6 months tested positive for high-level gentamicin resistant enterobacteriaceae or enterococci (MIC >128 mg/L).|
- Abnormalities of the upper urinary tract, including presence of urinary stones.
- Patients with a permanent urinary catheter.
- Complete urinary incontinence.
- Patients with stage 5 chronic kidney disease (GFR <15 ml/min).
- Patients with known hypersensitivity to gentamicin.
- Pregnancy or lactation.
- Inability to provide informed consent.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-apr-2014|
|- planned closingdate||1-apr-2016|
|- Target number of participants||170|
|- Interventions||Randomization 2:2:1:|
1. 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).
2. Low dose oral antibiotic prophylaxis based on prior susceptibility pattern of isolated uropathogens and patient characteristics, reflecting current standard care, for 24 weeks.
3. Wait and see policy without antimicrobial prophylaxis. In case of a first UTI after enrolment, patients will be randomized to study group 1 or 2.
|- Primary outcome||The number of UTI per patient after start of intravesical gentamicin or oral antibiotic prophylaxis during 6 months (period of prophylactic treatment) and 12 months (total follow up)|
|- Secondary outcome||The time to first, second and third symptomatic UTI after start of intravesical gentamicin or oral antibiotic prophylaxis; the proportion of patients with at least 1 UTI during 6 months of prophylactic treatment; the microbiological cure rate in male patients with chronic bacterial prostatitis; the need for oral/iv antibiotic-courses for UTI given in the hospital/daycare during the year of the study; antimicrobial resistance of urethral, perineal and vaginal flora before, during and after treatment; the rate of side effects and adverse events.|
Patientsí satisfaction with the treatment will be evaluated after 2, 12 and 24 weeks, and occurrence of urinary symptoms will be assessed every visit.
|- Timepoints||Follow up at wk 1, 2, 7-8, 12-14, 22-24, 34-36, 2 months, 3 months, 6 months, 9 months and 12 months.|
|- Trial web site|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||Drs. J.E. Stalenhoef|
|- CONTACT for SCIENTIFIC QUERIES||Drs. J.E. Stalenhoef|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Publications||van Nieuwkoop C, den Exter PL, Elzevier HW, den Hartigh J, van Dissel JT. Intravesical gentamicin for recurrent urinary tract infection in patients with intermittent bladder catheterisation. Int J Antimicrob Agents. 2010 Dec;36(6):485-90|
|- Brief 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.|
|- Main changes (audit trail)|
|- RECORD||16-jun-2014 - 29-mei-2016|