Clinical trial NCT04095572: Alternative Prophylaxis in Female Recurrent Urinary Tract Infections
Official title: Non-antimicrobial Alternative in Prophylaxis of Recurrent Urinary Tract Infections: a Prospective, Randomised-controlled, Double-blinded, Multicentre Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Urinary Tract Infections
Urinary Tract Infection (UTI)
Keywords: Hyaluronic acid (HA)
Chondroitin sulphate (CS)
antimicrobial resistance rates
Intravesical instillation
HA-CS instillations
Recurrent Urinary Tract Infection (rUTI)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: IBSA Institut Biochimique SA
First posted: 2019-09-19
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, parallel arm, superiority, multicentre, randomised trial with blinded treating physicians, patients and outcome assessors
Primary purpose: TREATMENT

Brief summary: Urological pathogens are effected by rising antimicrobial resistance rates due to the frequent use of antimicrobials for treatment and prophylaxis. Intravesical instillation with hyaluronic acid (HA) and chondroitin sulphate (CS) obtained positive outcomes in the treatment of overactive bladder, radiation cystitis and interstitial cystitis by replenishment of the glycosaminoglycan layer of the bladder. This study is to investigate whether intravesical instillation with HA-CS in patients with recurrent urinary tract infections (rUTI) is superior to a placebo instillation in terms of reduction of rate of symptomatic urinary tract infections (UTIs) (based on clinical diagnosis) needing treatment with antimicrobials within 12 months after randomisation.


Eligibility criteria: Inclusion Criteria:

* Documented history of rUTI, defined as ≥ 3 episodes of (un)complicated UTI documented by urine culture with the isolation of ≥103 cfu/ml of an identified pathogen in the last year with clinical symptoms OR 2 episodes in the last 6 month

Exclusion Criteria:

* No informed consent
* Concomitant UTI (\< 7 days prior to randomisation)
* Ongoing antimicrobial prophylaxis (e.g. for rUTI or for any other reason like endocarditis, transplanted patients under immunosuppression)
* Ongoing prophylactic strategy (e.g. immunoactive prophylaxis)
* Documented underlying urogenital abnormality (e.g. significant post voiding residual volume (\>50 ml), urethral stricture, urethral diverticula, urinary stone, reflux, urinary neoplasia), urological device (e.g. catheter, ureteral stent) or symptomatic pelvic floor disorder (e.g. genital prolapse stage ≥ II)
* Concomitant disease (i.e. renal insufficiency, diabetes mellitus, corticosteroid use)
* Urogenital urological or gynecological surgery \< 6 weeks
* Known allergy to the study medication
* Use of spermicides or intrauterine device
* Pregnancy

Primary outcomes:
measure: Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials
timeFrame: within 12 months after randomisation
Secondary outcomes:
measure: Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials
timeFrame: at screening and at each instillation visit (week 1 = Randomization, week 2, week 3, week 4, week 6, week 8, week 12) and at follow-up visits after randomization (month 6, month 9, month 12)
measure: Symptoms of UTI according to the Acute Cystitis Symptom Score (ACSS) (cumulative number of each symptom)
timeFrame: at screening and at each instillation visit (week 1 = Randomization, week 2, week 3, week 4, week 6, week 8, week 12) and at follow-up visits after randomization (month 6, month 9, month 12)
measure: Time to UTI recurrence (as days between randomisation and the first recurring UTI)
timeFrame: at screening and at each instillation visit (week 1 = Randomization, week 2, week 3, week 4, week 6, week 8, week 12) and at follow-up visits after randomization (month 6, month 9, month 12)
measure: Asymptomatic bacteriuria of ≥105 cfu/ml
timeFrame: at each instillation visit (week 1 = Randomization, week 2, week 3, week 4, week 6, week 8) if the urine dipstick is suspicious, at the 7th instillation (= week 12 )and at 12 month follow-up
measure: Detection of multidrug-resistant bacteria in urine culture (3Multiresistant gram negatives (MRGN), 4MRGN)
timeFrame: at screening and at at each instillation visit (week 1 = Randomization, week 2, week 3, week 4, week 6, week 8, week 12) and at follow-up visits after randomization (month 6, month 9, month 12)
measure: Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)
timeFrame: from randomisation to 12 months
measure: Change in Pelvic Pain and Urinary/Frequency (PUF) Symptom Scale
timeFrame: prior to randomisation and at 1 month, 3 months, 6 months, 9 months, 12 months
measure: Change in QoL Short Form (SF)-36 score
timeFrame: prior to randomisation and at 12 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department of Gynecology, University Hospital Basel
city: Basel
country: Switzerland
facility: Department of Urology, University Hospital Basel
Study officials:
affiliation: Department of Urology, University Hospital Basel
name: Kathrin Bausch, Dr. med
role: PRINCIPAL_INVESTIGATOR
References: