Back to resultsAlternative Prophylaxis in Female Recurrent Urinary Tract Infections (AlP-FrUiT)
Primary Purpose
Urinary Tract Infections, Urinary Tract Infection (UTI)
Status
Recruiting
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
intravesical instillation with HA-CS
intravesical instillation of sterile purified water
Sponsored by
About this trial
This is an interventional treatment trial for Urinary Tract Infections focused on measuring Hyaluronic acid (HA), Chondroitin sulphate (CS), antimicrobial resistance rates, Intravesical instillation, HA-CS instillations, Recurrent Urinary Tract Infection (rUTI)
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
Sites / Locations
- Department of Gynecology, University Hospital BaselRecruiting
- Department of Urology, University Hospital BaselRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
intervention group A
control group B
Arm Description
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
50 ml sterile purified water weekly for four weeks, then every second week in the second month and four weeks later
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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)
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.
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)
Asymptomatic bacteriuria of ≥105 cfu/ml
Asymptomatic bacteriuria, measured by number of colony forming Units (cfu) of ≥105 cfu/ml
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)
Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)
Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)
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
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.
Full Information
NCT ID
NCT04095572
First Posted
September 17, 2019
Last Updated
November 1, 2021
Sponsor
University Hospital, Basel, Switzerland
Collaborators
IBSA Institut Biochimique SA
1. Study Identification
Unique Protocol Identification Number
NCT04095572
Brief Title
Alternative Prophylaxis in Female Recurrent Urinary Tract Infections
Acronym
AlP-FrUiT
Official Title
Non-antimicrobial Alternative in Prophylaxis of Recurrent Urinary Tract Infections: a Prospective, Randomised-controlled, Double-blinded, Multicentre Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 27, 2020 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
Collaborators
IBSA Institut Biochimique SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Pragmatic, parallel arm, superiority, multicentre, randomised trial with blinded treating physicians, patients and outcome assessors
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
intervention group A
Arm Type
Active Comparator
Arm Description
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
Arm Title
control group B
Arm Type
Placebo Comparator
Arm Description
50 ml sterile purified water weekly for four weeks, then every second week in the second month and four weeks later
Intervention Type
Drug
Intervention Name(s)
intravesical instillation with HA-CS
Intervention Description
intravesical instillation with HA-CS (Ialuril Prefill®, IBSA Farmaceutici Italia Srl, Lodi, Italy)
Intervention Type
Drug
Intervention Name(s)
intravesical instillation of sterile purified water
Intervention Description
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 Measure Information:
Title
Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials
Description
Rate of symptomatic UTIs (based on clinical diagnosis) needing treatment with antimicrobials (cumulative number)
Time Frame
within 12 months after randomisation
Secondary Outcome Measure Information:
Title
Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials
Description
Symptomatic UTI (based on clinical diagnosis supported by measured bacteriuria of ≥103 cfu/ml) treated with antimicrobials (cumulative number)
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)
Title
Symptoms of UTI according to the Acute Cystitis Symptom Score (ACSS) (cumulative number of each symptom)
Description
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 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)
Title
Time to UTI recurrence (as days between randomisation and the first recurring UTI)
Description
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)
Title
Asymptomatic bacteriuria of ≥105 cfu/ml
Description
Asymptomatic bacteriuria, measured by number of colony forming Units (cfu) 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
Title
Detection of multidrug-resistant bacteria in urine culture (3Multiresistant gram negatives (MRGN), 4MRGN)
Description
Detection of multidrug-resistant bacteria in urine culture (3MRGN, 4MRGN) (yes/no)
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)
Title
Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)
Description
Prescribed defined daily doses (DDD) of antibiotics (cumulative sum of DDD)
Time Frame
from randomisation to 12 months
Title
Change in Pelvic Pain and Urinary/Frequency (PUF) Symptom Scale
Description
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
Time Frame
prior to randomisation and at 1 month, 3 months, 6 months, 9 months, 12 months
Title
Change in QoL Short Form (SF)-36 score
Description
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.
Time Frame
prior to randomisation and at 12 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kathrin Bausch, Dr. med
Phone
+41 61 265 72 80
Email
kathrin.bausch@usb.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Hans-Helge Seifert, Prof. Dr. MD
Phone
+41 61 265 72 80
Email
helge.seifert@usb.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathrin Bausch, Dr. med
Organizational Affiliation
Department of Urology, University Hospital Basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Gynecology, University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tilemachos Kavvadias, Dr. med
Phone
+41 61 265 93 93
Email
tilemachos.kavvadias@usb.ch
Facility Name
Department of Urology, University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathrin Bausch, Dr. med
Phone
+41 61 265 72 80
Email
kathrin.bausch@usb.ch
First Name & Middle Initial & Last Name & Degree
Hans-Helge Seifert, Prof. Dr. MD
Phone
+41 61 265 72 80
Email
helge.seifert@usb.ch
First Name & Middle Initial & Last Name & Degree
Linda Maria Stamm
12. IPD Sharing Statement
Learn more about this trial
Alternative Prophylaxis in Female Recurrent Urinary Tract Infections
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