Alternative Prophylaxis in Female Recurrent Urinary Tract Infections (AlP-FrUiT)

Non-antimicrobial Alternative in Prophylaxis of Recurrent Urinary Tract Infections: a Prospective, Randomised-controlled, Double-blinded, Multicentre Study

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.

Study Overview

• Status: Recruiting
• Conditions: Urinary Tract Infections; Urinary Tract Infection (UTI)
• Intervention / Treatment: Drug: intravesical instillation with HA-CS; Drug: intravesical instillation of sterile purified water

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kathrin Bausch, Dr. med; Phone Number: +41 61 265 72 80; Email: kathrin.bausch@usb.ch
• Study Contact Backup: Name: Hans-Helge Seifert, Prof. Dr. MD; Phone Number: +41 61 265 72 80; Email: helge.seifert@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Department of Gynecology, University Hospital Basel
    • Contact: Tilemachos Kavvadias, Dr. med; Phone Number: +41 61 265 93 93; Email: tilemachos.kavvadias@usb.ch
  • Basel, Switzerland, 4031
    • Recruiting
    • Department of Urology, University Hospital Basel
    • Contact: Kathrin Bausch, Dr. med; Phone Number: +41 61 265 72 80; Email: kathrin.bausch@usb.ch
    • Contact: Hans-Helge Seifert, Prof. Dr. MD; Phone Number: +41 61 265 72 80; Email: helge.seifert@usb.ch
    • Sub-Investigator: Linda Maria Stamm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: intervention group A; 50 ml of a sterile sodium HA (800 mg)- CS (1g) solution (Ialuril Prefill®, IBSA Farmaceutici Italia Srl, Via Martiri di Cefalonia 2, 26900 Lodi, Italy) weekly for four weeks, then every second week in the second month and four weeks later	Drug: intravesical instillation with HA-CS; intravesical instillation with HA-CS (Ialuril Prefill®, IBSA Farmaceutici Italia Srl, Lodi, Italy)
Placebo Comparator: control group B; 50 ml sterile purified water weekly for four weeks, then every second week in the second month and four weeks later	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials	Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials (cumulative number)	within 12 months after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials	Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials (cumulative number)	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)	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.	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 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)
Asymptomatic bacteriuria of ≥105 cfu/ml	Asymptomatic bacteriuria, measured by number of colony forming Units (cfu) 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
Detection of multidrug-resistant bacteria in urine culture (3Multiresistant gram negatives (MRGN), 4MRGN)	Detection of multidrug-resistant bacteria in urine culture (3MRGN, 4MRGN) (yes/no)	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)	Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)	from randomisation to 12 months
Change in Pelvic Pain and Urinary/Frequency (PUF) Symptom Scale	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	prior to randomisation and at 1 month, 3 months, 6 months, 9 months, 12 months
Change in QoL Short Form (SF)-36 score	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.	prior to randomisation and at 12 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: IBSA Institut Biochimique SA
• Investigators: Principal Investigator: Kathrin Bausch, Dr. med, Department of Urology, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2020
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Hyaluronic acid (HA); Intravesical instillation; Chondroitin sulphate (CS); antimicrobial resistance rates; HA-CS instillations; Recurrent Urinary Tract Infection (rUTI)
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections
• Other Study ID Numbers: 2019-01377; me19Bausch

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No