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ID
Source
Brief title
Health condition
Urinary tract infections
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical cure rate (i.e., resolution of symptoms and fever) among evaluable patients through the 10- to 18-day posttherapy visit.
Secondary outcome
10-18 days post-treatment:
- bacteriologic cure rate i.e. urine culture
- all-cause mortality
- adverse events
70- to 84 days post-treatment:
- clinical cure rate
- all-cause mortality
- relapse rate of UTI
- The plasma concentration of fosfomycin (mg/L) + 1, 1.5, 3, 5, and 8 hours after
the first study administration
- The plasma concentration of fosfomycin (mg/L) just before, +1, 1.5, 2, 3 hours
after third study administration or later
- The urine concentration of fosfomycin (mg/L), as measured following the
methods (section 5) 1-24 hours after the first study administration
- The urine concentration of fosfomycin (mg/L) 48-72 hours after the first study
administration or later
Background summary
Rationale: Due to rising resistance of Enterobacteriaceae against the orally available
antibiotics ciprofloxacin and trimethoprim-sulfamethoxazole, difficulties arise in the treatment
of febrile urinary tract infection (FUTI) in men. Fosfomycin possesses a high bactericidal
activity to Escherichia coli with resistance rates of 1%. Fosfomycin 3000mg, dosed every 24
hours, reaches sufficient antibiotic levels in urine, prostate and bladder, has good tolerability
and is considered safe. Therefore, fosfomycin is a potential alternative antibiotic option for
treatment of FUTI in men.
Objective: To determine the efficacy of oral fosfomycin, in the treatment of FUTI after initial
empirical treatment with intravenous antibiotics.
Study design: An open label multicenter pilot study
Study population: Consenting men (≥18 years), on appropriate intravenous therapy for
FUTI caused by E. coli and fulfilling criteria for an iv-to-oral switch.
Intervention: After an empirical intravenous antibiotic treatment an iv-oral switch to oral
fosfomycin 3000mg, every 24 hours, up to 14 days. Patients will be compared to historical
controls who were included in a randomized trial with similar inclusion criteria and who were
treated with oral ciprofloxacin.
Eligible patients who refuse to be treated with fosfomycin, will be treated with ciprofloxacin.
Those patients will be asked to participate in the trial for observational purposes only as they
can serve as control patients as well.
Main study parameters/endpoints: The primary endpoint is the clinical cure rate (resolution
of symptoms) 10 to 18 days post-treatment (= test of cure, TOC). Secondary endpoints are
clinical cure rate during late follow-up (LFU, 70 to 84 days post-treatment), microbiological
cure rate, time to resolution of symptoms, rate of UTI relapse and rate of adverse events. A pharmacokinetic substudy is part of the study and end points are blood and urine concentrations of fosfomycin after oral ingestion.
Study objective
Oral fosfomycin efficacy is as good as ciprofloxacin in men with E. coli FUTI after initial empirical treatment with intravenous antibiotics.
Study design
The primary outcome will be assesed on day 24-32. Secondary outcomes will be assesed on day 24-32 and 84-94.
Plasma pharmacokinetics data will be assesed at day 0 and day 3 till day 14.
Intervention
Oral fosfomycin 3 gram each 24 hours with duration of 14 days minus days of intravenous antibiotic,
Inclusion criteria
1. Competent male patient aged 18 years or above
2. One or more symptom(s) suggestive of urinary tract infection (dysuria, frequency or
urgency; perineal or suprapubic pain; costo-vertebral tenderness or flank pain)
3. Fever (ear or rectal temp of 38.2 oC or higher, or axillary temp of 38 oC or higher), or
history of feeling feverish with shivering or rigors in the past 24 hours
4. Positive urine nitrate test and/or leucocyturia as depicted by positive leukocyte
esterase test or microscopy
5. Hospital admission for presumed FUTI and empirical intravenous antibiotic treatment
with beta-lactams
6. Positive urine (> 103 CFU/ml) culture and/or blood culture with E. coli susceptible to
fosfomycin, ciprofloxacin and the empirical intravenous beta-lactam treatment
7. Fullfilment of criteria for safe iv to oral switch (hemodynamic stability, ability to
consume oral antibiotics, no gastrointestinal problems which affect absorption)
Exclusion criteria
1. Known allergy to fosfomycin or ciprofloxacin
2. Patients with known polycystic kidney disease
3. Patients on permanent renal replacement therapy (hemodialysis or peritoneal
dialysis)
4. Patients with history of kidney transplantation
5. Patients with a permanent urinary catheter
6. Patients with chronic renal failure (eGFR < 30 ml/min/1.73m3)
7. Patients with renal abcess or pyonephrosis
8. Patients with chronic bacterial prostatitis (defined as recurrent UTI with the same
uropathogen and no other clarifying underlying urological disorder)
9. Patients with any diagnosed metastatic E. coli foci
10. Patients with a double-J or nephrostomy catheter
11. Concomitant systemic antibiotic treatment for another reason than FUTI
12. Residence outside the Netherlands
13. Inability to speak or read Dutch
Specific exclusion criteria for the FOS-MEN-pharm substudy is
1. Incontinency for urine, which results in the inability to properly get urine samples.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| NTR-new | NL8728 |
| Other | METC Leiden-Den Haag-Delft. : 18-105 |