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

Phase 4

Recruiting

• Conditions: Recurrent Urinary Tract Infection
• Interventions: Device: Ialuril 50ml Prefill; Drug: Nitrofurantoin

• Registration Number: NCT05652374
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study Start: 2022-10-20
• Study First Submitted: 2022-11-23
• Study First Submitted QC: 2022-12-14
• Study First Posted: 2022-12-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Primary Completion: 2027-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	Ialuril 50ml Prefill	Ialuril therapy for 6 months followed by nitrofuranoïne (or trimethoprim) prophylactic therapy for 6 months. In between therapies there is a 4 week wash-out period.
Group A	Nitrofurantoin	Ialuril therapy for 6 months followed by nitrofuranoïne (or trimethoprim) prophylactic therapy for 6 months. In between therapies there is a 4 week wash-out period.
Group B	Ialuril 50ml Prefill	Nitrofuranoïne (or trimethoprim) prophylactic therapy for 6 months followed by Ialuril therapy for 6 months. In between therapies there is a 4 week wash-out period.
Group B	Nitrofurantoin	Nitrofuranoïne (or trimethoprim) prophylactic therapy for 6 months followed by Ialuril therapy for 6 months. In between therapies there is a 4 week wash-out period.

Primary Outcome Measures

Name	Time	Method
Number of urinary tract infections	13 months	Number of urinary tract infections per patient-year

Secondary Outcome Measures

Name	Time	Method
Time to first urinary tract infection	13 months	Time to first urinary tract infection
Global Assessment of Improvement	7 weeks, 3 months, 6 months after start of each therapy	Changes on Global Assessment of Improvement, Likert scale: -3 (worst) to +3(best)
Antibiotics resistance	Baseline, 6 months after start of each therapy	Difference in acquired AB resistance (increase in resistance to different antibiotic treatments) between both patients groups
Cost-effectiveness: medical consumption questionnaire	Baseline, 6 months after start of each therapy	Difference in cost-effectiveness between the 2 therapies. This is assessed with the 'medical consumption questionnaire'
Cost-effectiveness: productivity cost questionnaire	Baseline, 6 months after start of each therapy	Difference in cost-effectiveness between the 2 therapies. This is assessed with the 'productivity cost questionnaire'
Therapy specific patient reported outcomes (symptoms & bother)	baseline, 7 weeks, 3 months, 6 months after start of each therapy	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)
General quality of life questionnaire (mobility, self-care, daily activities, pain/discomfort, anxiety/depression)	baseline, 7 weeks, 3 months, 6 months after start of each therapy	Is there a difference in the Quality-of-life between the 2 therapies during follow-up using ED-5D 5L questionnaire

Trial Locations

Locations (3)

Rijnstate ziekenhuis; 🇳🇱 Arnhem, Netherlands

Canisius wilhelmina ziekenhuis; 🇳🇱 Nijmegen, Netherlands

Radboudumc; 🇳🇱 Nijmegen, Gelderland, Netherlands