Urinary Tract Infections, Urinary Tract Infection (UTI)
Conditions
Keywords
Hyaluronic acid (HA), Chondroitin sulphate (CS), antimicrobial resistance rates, Intravesical instillation, HA-CS instillations, Recurrent Urinary Tract Infection (rUTI)
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.
Interventions
DRUGintravesical instillation with HA-CS
intravesical instillation with HA-CS (Ialuril Prefill®, IBSA Farmaceutici Italia Srl, Lodi, Italy)
DRUGintravesical 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)
Sponsors
IBSA Institut Biochimique SA
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Pragmatic, parallel arm, superiority, multicentre, randomised trial with blinded treating physicians, patients and outcome assessors
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials | within 12 months after randomisation | Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials (cumulative number) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms of UTI according to the Acute Cystitis Symptom Score (ACSS) (cumulative number of each symptom) | 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) | Change in Acute Cystitis Symptom Score (ACSS). The first part of the ACSS questionnaire consists of 14 questions. The first 6 questions assess typical symptoms of UTI: frequency, urgency, pain and burning during urination, sensation of incomplete bladder emptying, pain/discomfort in the lower abdomen, visible hematuria. Each question concerning urinary symptoms allows the patient to choose one out of four answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 3. The score can range between 0 and 18. It has been validated and a score ≥ 6 seems to be very indicative for the diagnosis of an UTI. |
| Time to UTI recurrence (as days between randomisation and the first recurring UTI) | 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) |
| Asymptomatic bacteriuria of ≥105 cfu/ml | 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 | Asymptomatic bacteriuria, measured by number of colony forming Units (cfu) of ≥105 cfu/ml |
| Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials | 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) | Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials (cumulative number) |
| Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD) | from randomisation to 12 months | Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD) |
| Change in Pelvic Pain and Urinary/Frequency (PUF) Symptom Scale | prior to randomisation and at 1 month, 3 months, 6 months, 9 months, 12 months | The PUF questionnaire consists of 12 questions. The first two questions allow the patient to choose one out of five answers (points 0-3), the following questions one out of four (points 0-3) indicating increasing severity of the particular symptom. Seven of the questions concern symptoms (total count 23), four questions are part of the bother score (total count 12). Total score consists of symptom score and bother score (total count 35). The change of the score is calculated by subtracting the score at 1 month, 3 months, 6 months, 9 months, 12 months from the score at enrolment |
| Change in QoL Short Form (SF)-36 score | prior to randomisation and at 12 months | The QoL SF-36 consists of 36 items including eight independent scales and two main dimensions 35 of the items are compressed into eight multi-item scales: (1) physical functioning is a ten-question scale; (2) role-physical is a four-item scale; (3) bodily pain is a two-item scale; (4) general health is a five-item scale; (5) vitality is a four-item scale; (6) social functioning is a two-item scale; (7) role-emotional is a three-item scale; and (8) mental health is a five-item scale. Hence, in the SF-36 scoring system, the scales are assessed quantitatively, each on the basis of answers to two to ten multiple choice questions, and a score between 0 and 100 is then calculated on the basis of well-defined guidelines, with a higher score indicating a better state of health. The change of the score is calculated by subtracting the score at 12 month from the score at enrolment. |
| Detection of multidrug-resistant bacteria in urine culture (3Multiresistant gram negatives (MRGN), 4MRGN) | 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) | Detection of multidrug-resistant bacteria in urine culture (3MRGN, 4MRGN) (yes/no) |
Countries
Switzerland
Contacts
Primary ContactKathrin Bausch, Dr. med
Backup ContactHans-Helge Seifert, Prof. Dr. MD
Outcome results
None listed