Gag Therapy for Recurrent Urinary Tract Infection Assessing Comparability to International Nitrofurantoin Gold Standard Study (GT RACING)

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).

Study Overview

• Status: Recruiting
• Conditions: Recurrent Urinary Tract Infection
• Intervention / Treatment: Device: Ialuril 50ml Prefill; Drug: Nitrofurantoin

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dick Janssen, MD, PhD; Phone Number: +31 6 41856516; Email: dick.janssen@radboudumc.nl
• Study Contact Backup: Name: Cléo Baars, MD; Phone Number: +31 6 15400527; Email: cleo.baars@radboudumc.nl

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Recruiting
    • Rijnstate Ziekenhuis
    • Contact: Michael van Balken; Phone Number: +31880058888; Email: mvanbalken@rijnstate.nl
  • Nijmegen, Netherlands
    • Recruiting
    • Canisius Wilhelmina Ziekenhuis
    • Contact: Rianne Hendriks; Phone Number: +31243658961; Email: r.hendriks@cwz.nl
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Radboudumc
      • Contact: Cléo Baars, MD; Phone Number: +31 6 15400527; Email: cleo.baars@radboudumc.nl
      • Contact: Dick Janssen, MD, PhD; Phone Number: +31641856516; Email: dick.janssen@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A; 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.	Device: Ialuril 50ml Prefill; 50ml of sterile Ialuril (HA 1.6% CS 2%) bladder instillations weekly for 6 weeks, followed by monthly maintenance therapy for 6 months; Other Names: HA-CS; Drug: Nitrofurantoin; nitrofurantoin 100mg daily (1dd100mg or 2dd50mg) for 6 months. ( In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily)
Other: Group B; 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.	Device: Ialuril 50ml Prefill; 50ml of sterile Ialuril (HA 1.6% CS 2%) bladder instillations weekly for 6 weeks, followed by monthly maintenance therapy for 6 months; Other Names: HA-CS; Drug: Nitrofurantoin; nitrofurantoin 100mg daily (1dd100mg or 2dd50mg) for 6 months. ( In case of resistance/intolerance/allergy for nitrofurantoin alternatively trimethoprim 100mg daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of urinary tract infections	Number of urinary tract infections per patient-year	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first urinary tract infection	Time to first urinary tract infection	13 months
Global Assessment of Improvement	Changes on Global Assessment of Improvement, Likert scale: -3 (worst) to +3(best)	7 weeks, 3 months, 6 months after start of each therapy
Antibiotics resistance	Difference in acquired AB resistance (increase in resistance to different antibiotic treatments) between both patients groups	Baseline, 6 months after start of each therapy
Cost-effectiveness: medical consumption questionnaire	Difference in cost-effectiveness between the 2 therapies. This is assessed with the 'medical consumption questionnaire'	Baseline, 6 months after start of each therapy
Cost-effectiveness: productivity cost questionnaire	Difference in cost-effectiveness between the 2 therapies. This is assessed with the 'productivity cost questionnaire'	Baseline, 6 months after start of each therapy
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, 3 months, 6 months after start of each therapy
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, 3 months, 6 months after start of each therapy

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: IBSA Institut Biochimique SA; Goodlife Pharma B.V.
• Investigators: Principal Investigator: Dick Janssen, MD, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Prophylactic antibiotics; GAG therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Recurrence; Infections; Communicable Diseases; Urinary Tract Infections; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Infective Agents, Urinary; Nitrofurantoin
• Other Study ID Numbers: 111802; NL76892.091.21 (Other Identifier: algemeen beoordelings- en registratie)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: only anonymous patient data will be shared

Drug and device information, study documents

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