Clinical trial NCT05652374: Gag Therapy for Recurrent Urinary Tract Infection Assessing Comparability to International Nitrofurantoin Gold Standard Study
Official title: Gag Therapy for Recurrent Urinary Tract Infection Assessing Comparability to International Nitrofurantoin Gold Standard Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Recurrent Urinary Tract Infection
Keywords: GAG therapy
Prophylactic antibiotics
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: IBSA Institut Biochimique SA
name: Goodlife Pharma B.V.
First posted: 2022-12-15
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cross-over randomized controlled trial. Study is set-up as non-inferiority, parallel group trial, with a 1:1 randomization.
Primary purpose: PREVENTION

Brief summary: The GT RACING is a study comparing the efficacy of HA-CS bladder installations with prophylactic antibiotics in the prevention of recurrent urinary tract infections (rUTI).

Detailed description: The main objective of the study is to compare efficacy between hyaluronic acid - chondroitin sulphate (HA-CS) treatment and gold standard treatment (AB prophylaxis). Study is set-up as non-inferiority, parallel group cross-over RCT, with a 1:1 randomization.

Study population: Female (\>18rs) with at least 3 symptomatic urinary tract infections (UTI's) in the previous year with no adequate curable therapeutic options.

Intervention: 50ml of sterile Ialuril (HA 1.6% CS 2%) weekly for 6 weeks, followed by monthly maintenance therapy for 6 months.

Control : oral nitrofurantoin 100mg daily (1dd100mg or 2dd50mg) for 6 months. In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily will be given.

All patients recieve both treatments (ialuril and nitrofurantoin) consecutively, for 6 months each. The order of the therapies is determined by randomisation. Between therapies there is a 4 weeks 'wash-out' period. A total of 100 patients will be included.

During the study patients will fill-out questionnaires regarding symptoms, quality of life and use of healthcare. Furthermore urine will be collected at set timepoints.

Main study parameters/endpoints: The main study parameter is the number of UTI per patient-year. Secondary parameters are time to rUTI (wks.), outcome on the global responce assessment (GRA) scale, pattern of antibiotic resistance, outcome on the patient reported outcome questionnaire, cost effectiveness and Quality-of-life.

Eligibility criteria: Inclusion Criteria:

1. Adult female patients (\>18 years) who had at least 3 symptomatic UTI's in the previous year with no adequate curable therapeutic options (e.g. bladder stones)
2. At least one UTI's must be confirmed with a positive culture and antibiogram, further UTI's must be confirmed with a urine sediment with positive nitrite or a positive culture.

Exclusion Criteria:

1. Male
2. \< 18 years
3. Pregnant
4. Already on GAG therapy
5. Already on prophylactic antibiotics
6. Started or stopped cranberry/d-mannose therapy or vaginal estrogenic creme in the last two months
7. Had Gentamicin or other antibiotic instillations in the previous 2 months
8. Allergic to \>3 regular used antibiotics in Dutch guidelines (ed. Nitrofurantoin, trimethoprim, Fosfomycin)
9. A urinary fistula
10. Urinary stones
11. Urogenital cancer
12. Bladder Pain Syndrome - Interstitial Cystitis
13. Chronic pelvic pain
14. Had a STD untreated or treated in the previous 2 months
15. A urinary diversion
16. An Indwelling catheter
17. A suprapubic catheter
18. Performing \>1/day self-catheterization
19. A residue after voiding (PVR) of \>200ml
20. Unable (also legal) to give informed consent
21. Recurrent urosepsis
22. Multiresistant bacteria in previous urine cultures
23. Contra-indications and interactions for Nitrofurantoin: severe kidney disfunction (GFR \< 30), lung- or liver problems or neuropathy after previous use of nitrofurantoin, acute porphyria, known G6PD deficiency, use of magnesium trisilicate.
24. Contra-indications and interactions for trimethoprim: severe kidney or liver dysfunction, blood count abnormality, use of vitamin K antagonists, use of folic acid antagonists, use of ace inhibitors
25. Severe lung/respiratory disfunction (reduced lung capacity, lung cancer, fibrosis, COPD)
26. Does not tolerate catheterization

Primary outcomes:
measure: Number of urinary tract infections
timeFrame: 13 months
Secondary outcomes:
measure: Time to first urinary tract infection
timeFrame: 13 months
measure: Global Assessment of Improvement
timeFrame: 7 weeks, 3 months, 6 months after start of each therapy
measure: Antibiotics resistance
timeFrame: Baseline, 6 months after start of each therapy
measure: Cost-effectiveness: medical consumption questionnaire
timeFrame: Baseline, 6 months after start of each therapy
measure: Cost-effectiveness: productivity cost questionnaire
timeFrame: Baseline, 6 months after start of each therapy
measure: Therapy specific patient reported outcomes (symptoms & bother)
timeFrame: baseline, 7 weeks, 3 months, 6 months after start of each therapy
measure: General quality of life questionnaire (mobility, self-care, daily activities, pain/discomfort, anxiety/depression)
timeFrame: baseline, 7 weeks, 3 months, 6 months after start of each therapy
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Arnhem
country: Netherlands
facility: Rijnstate ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius wilhelmina ziekenhuis
Study officials:
affiliation: Radboud University Medical Center
name: Dick Janssen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: