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

Overview

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.

Interventions

• Drug intravesical instillation with HA-CS
  intravesical instillation with HA-CS (Ialuril Prefill®, IBSA Farmaceutici Italia Srl, Lodi, Italy)
• Drug intravesical instillation of sterile purified water
  intravesical instillation of sterile purified water (packed and labelled according to Good Manufacturing Practice at IBSA Farmaceutici Italia Srl in Lodi, Italy to provide adequate blinding)

Primary outcome measures

• Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials [Time frame: within 12 months after randomisation]

Secondary outcome measures (8)

• Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials [Time frame: 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)]
• Symptoms of UTI according to the Acute Cystitis Symptom Score (ACSS) (cumulative number of each symptom) [Time frame: 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)]
• Time to UTI recurrence (as days between randomisation and the first recurring UTI) [Time frame: 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)]
• Asymptomatic bacteriuria of ≥105 cfu/ml [Time frame: 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]
• Detection of multidrug-resistant bacteria in urine culture (3Multiresistant gram negatives (MRGN), 4MRGN) [Time frame: 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)]
• Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD) [Time frame: from randomisation to 12 months]
• Change in Pelvic Pain and Urinary/Frequency (PUF) Symptom Scale [Time frame: prior to randomisation and at 1 month, 3 months, 6 months, 9 months, 12 months]
• Change in QoL Short Form (SF)-36 score [Time frame: prior to randomisation and at 12 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Switzerland · 2 centers

• Department of Gynecology, University Hospital Basel — Basel
• Department of Urology, University Hospital Basel — Basel

Identifiers

NCT: NCT04095572 · 2019-01377; me19Bausch

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗