gag therapy for recurrent urinary tract infection assessing comparability to international nitrofurantoin gold standard study

Conditions: Recurrent Urinary Tract Infection

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).

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

Keywords: gag therapy prophylactic antibiotics