Acute febrile urinary tract infection MedDRA version: 20.0 Level: LLT Classification code 10046574 Term: Urinary tract infection NOS System Organ Class: 100000017512 MedDRA version: 20.0 Level: LLT Classification code 10046576 Term: Urinary tract infection, site not specified System Organ Class: 100000017512
Conditions
Interventions
Trade Name: Monuril 3000 mg, granulaat voor drank
(Generic name: Fosfomycin-trometamol)
Pharmaceutical Form:
Pharmaceutical form of the placebo: Powder and solvent for oral solution
Route of administ
Sponsors
University Medical Centre Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Hospitalised -Competent women (=18 years), able to give informed consent -AF-UTI as presumptive diagnosis and primary reason for hospitalisation* -Adequate intravenous antibiotic therapy for =48 - =120 hours** -Candidate for safe iv to oral switch as judged by the attending physician -Urine (=104 CFU/ml) OR blood culture obtained within 24 hours before or after admission: Escherichia coli , ciprofloxacin S AND fosfomycin S*** * Acute Febrile Urinary Tract Infections (AF-UTI) are UTI with at least one of the forthcoming systemic symptoms: fever or low temperature (=38.0 C ? or =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: -Pregnant or nursing women -Glomerular filtration rate < 30 ml/min/1,73 m3 or renal replacement therapy -Concomitant systemic antibacterial treatment # -Ascertained or presumptive hypersensitivity to the active compounds and/or any excipient of the products or to any quinole -Participation to any trial with an investigational product involved in the 30 days before the screening visit -Every other laboratory result, clinical condition, disease or treatment that, in investigator’s opinion, make the subject non suitable for the study -Specific comorbidity or diagnosis## -Contraindications/interactions for any of the active compounds or medication ### -Patients with inadequate understanding of the study risks or its requirements or unwilling to plan a follow-up visit # If prophylactic antibiotic therapy could not be paused during study therapy, the patient should be excluded Except for continuation of prophylactic antibacterial therapy ## Renal transplant patients, polycystic kidney disease, neutropenia (<500 /µl), paraplegia, long-term indwelling catheters (placed =24 hours before admission), urostomy, ileal loops, double-J catheter, nephrostomy catheter, suprapubic catheter, suspicion/presence of renal abscess, suspicion of septic metastatic foci/endocarditis ### Concurrent use of Tizanidin, Clozapin or Theophylline. If pausing or conversion of this medicine disadvantages the participant, she will be excluded. Patients with a history of tendon disease/disorder related to quinolone treatment. Patients with known risk factors for prolongation of the QT interval. Glucose-6-phosphate dehydrogenase deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 6-10 days post-treatment ;Main Objective: To demonstrate non-inferiority of oral fosfomycin-trometamol compared to oral ciprofloxacin as a step-down treatment for E.coli AF-UTI in women for the cumulative incidence of survival and clinical cure (resolution of symptoms) 6-10 days post-treatment.;Primary end point(s): Primary endpoint: The primary endpoint is the cumulative incidence of clinical cure (resolution of symptoms, incl. survival) ;Secondary Objective: 1) To demonstrate non-inferiority of oral fosfomycin-trometamol compared to oral ciprofloxacin as a step-down treatment for E.coli AF-UTI in women on microbiological cure 6-10 days post-treatment, the cumulative incidence of early study discontinuation, the cumulative incidence of clinical cure, the cumulative incidence of mortality, ICU admittances, relapses, reinfections, readmissions, additional antibiotic treatment for Urinary Tract Infections (UTI), adverse events, the total days of hospitalisation and days of absenteeism within 30-35 days post-treatment. 2) to identify associations between patient/disease or treatment variables/and the primary endpoint 6-10 days post-treatment and ICU admission and mortality 30-35 days post-treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: 1. The cumulative incidence of microbiological cure 6-10 days post-treatment 2. The cumulative incidence of survival AND clinical cure (resolution of symptoms) AND microbiological cure 6-10 days post-treatment 3. The cumulative incidence of acquired fosfomycin resistance, ciprofloxacin resistance or ESBL-producing bacteria in urine culture 6-10 days post-treatment 4. The cumulative incidence of survival and clinical cure (resolution of symptoms) 30-35 days post-treatment 5. The cumulative incidence of mortality for any reason or related to UTI or study medicines within 30-35 days post-treatment 6. The cumulative incidence of ICU admissions for any reason or related to UTI or study medicines within 30-35 days post-treatment 7. The cumulative incidence of readmissions for any reason or related to UTI or study medicines within 30-35 days post-treatment 8. The cumulative incidence of relapses within 30-35 days post-treatment 9. The cumulative incidence of reinfections within 30-35 days post-treatment 10. The cumulative incidence of additional antibiotic use for UTI within 30-35 days post-treatment 11. The cumulative incidence of early discontinuation of study medicines because of adverse events OR because of loss of complaints 12. Total days of hospitalisation and Intensive Care Unit stay within 30-35 days post-treatment 13. The cumulative incidence of absenteeism within 30-35 days post-treatment 14. The cumulative incidence of study protocol related and unrelated adverse events, within 30-35 days post-treatment 15. Patient characteristics associated with the primary or secondary outcomes in both study arms (Charlson comorbidity index, Diabetes Mellitus y/n, indwelling catheter y/n, age </= 65 years, treatment restrictions at admission y/n, treatment restrictions at randomisation y/n, renal stones y/n) 16. Disease related characteristics associated with the primary or secondary outcomes in both study arms ( | — |
Countries
Netherlands
Contacts
Public ContactThijs ten Doesschate
University Medical Center Utrecht
Outcome results
None listed