Gag Therapy for Recurrent Urinary Tract Infection Assessing Comparability to International Nitrofurantoin Gold Standard Study

Study Overview
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Brief Summary
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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
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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 trial, 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: Intervention group (n=50): 50ml of sterile Ialuril (HA 1.6% CS 2%) weekly for 6 weeks, followed by monthly maintenance therapy for 1 year. Control group (n=50): oral nitrofurantoin 100mg daily (1dd100mg or 2dd50mg) for 1 year. In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily will be given. 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.

Official Title
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Gag Therapy for Recurrent Urinary Tract Infection Assessing Comparability to International Nitrofurantoin Gold Standard Study

Conditions
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Recurrent Urinary Tract Infection

Intervention / Treatment
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* Device: Ialuril 50ml Prefill
* Drug: Nitrofurantoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) 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: Male < 18 years Pregnant Already on GAG therapy Already on prophylactic antibiotics Started or stopped cranberry/d-mannose therapy or vaginal estrogenic creme in the last two months Had Gentamicin or other antibiotic instillations in the previous 2 months Allergic to >3 regular used antibiotics in Dutch guidelines (ed. Nitrofurantoin, trimethoprim, Fosfomycin) A urinary fistula Urinary stones Urogenital cancer Bladder Pain Syndrome - Interstitial Cystitis Chronic pelvic pain Had a STD untreated or treated in the previous 2 months A urinary diversion An Indwelling catheter A suprapubic catheter Performing >1/day self-catheterization A residue after voiding (PVR) of >200ml Unable (also legal) to give informed consent Recurrent urosepsis Multiresistant bacteria in previous urine cultures 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. 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 Severe lung/respiratory disfunction (reduced lung capacity, lung cancer, fibrosis, COPD) Does not tolerate catheterization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial. Study is set-up as non-inferiority, parallel group trial, with a 1:1 randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>50ml of sterile Ialuril (HA 1.6% CS 2%) bladder instillations weekly for 6 weeks, followed by monthly maintenance therapy for 1 year | Device: Ialuril 50ml Prefill<br>* Bladder instillations weekly for 6 weeks, followed by monthly maintenance therapy for 1 year<br>* Other names: HA-CS;|
| Active Comparator: Control group<br>nitrofurantoin 100mg daily (1dd100mg or 2dd50mg) for 1 year. In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily will be given. | Drug: Nitrofurantoin<br>* 100mg daily (1dd100mg or 2dd50mg) for 1 year. ( In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of urinary tract infections | Number of urinary tract infections per patient-year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first urinary tract infection | Time to first urinary tract infection | 1 year | 
| Global Assessment of Improvement | Changes on Global Assessment of Improvement, Likert scale: -3 (worst) to +3(best) | 7 weeks, 6 months and 12 months | 
| Antibiotics resistance | Difference in acquired AB resistance (increase in resistance to different antibiotic treatments) between both patients groups | Baseline, 6 months, 12 months | 
| Cost-effectiveness: medical consumption questionnaire | Difference in cost-effectiveness between the 2 therapies. This is assessed with the 'medical consumption questionnaire' | Baseline, 6 months, 12 months | 
| Cost-effectiveness: productivity cost questionnaire | Difference in cost-effectiveness between the 2 therapies. This is assessed with the 'productivity cost questionnaire' | Baseline, 6 months, 12 months | 
| Therapy specific patient reported outcomes (symptoms & bother) | Differences in therapy specific patient reported outcomes between both patient groups (measured in Therapy Specific Patient Reported Outcome (PRO) Questionnaire on Symptom & Bother rUTI & GAG therapy) | baseline, 7 weeks, 6 months, 9 months, 12 months | 
| General quality of life questionnaire (mobility, self-care, daily activities, pain/discomfort, anxiety/depression) | Is there a difference in the Quality-of-life between the 2 therapies during follow-up using ED-5D 5L questionnaire | baseline, 7 weeks, 6 months, 9 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GAG therapy, Prophylactic antibiotics