To determine the efficacy of oral fosfomycin in comparison to the standard of care oral ciprofloxacin, in the treatment of FUTI after initial empirical treatment with intravenous antibiotics.To describe the pharmokinetic profile of men treated with…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Urinary tract signs and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the clinical cure rate (resolution of symptoms) 10 to
18 days post-treatment (= test of cure, TOC).
Secondary outcome
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, rate of adverse events and the pharmacokinetic
profile of fosfomycin.
Background summary
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.
Study objective
To determine the efficacy of oral fosfomycin in comparison to the standard of
care oral ciprofloxacin, in the treatment of FUTI after initial empirical
treatment with intravenous antibiotics.
To describe the pharmokinetic profile of men treated with fosfomycin 3 gram
o.d.
Study design
An open label multicenter pilot study with historical controls
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.
Study burden and risks
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.
The burden for participants is considered low as patients are treated and
evaluated following current clinical practice guidelines and Good Clinical
Practice. This study is considered to be of low-risk for the following reasons;
the pathogen causing FUTI has documented susceptibility to fosfomycin; patients
are not acutely ill at the moment of randomization as they fulfil the criteria
for iv-oral switch (and indeed already had effective intravenous antibiotics)
and fosfomycin has a good safety profile. Fosfomycin has been used extensively
as single-dose oral therapy; previous studies have indicated that fosfomycin is
likely to be suitable for treating FUTI in men with a high bio-availability,
reaching sufficient levels in urine, prostate and bladder wall. Clinical cure
for FUTI has been described in case series. Furthermore, in case of clinical
failure of fosfomcycin the patient can always be treated with the gold standard
ciprofloxacin as this is part of the in- and exclusion criteria. Overall the
future benefit of this trial, obtaining a new antibiotic option for FUTI in
men, outweighs the low risks involved for participants.
Els Borst-Eilersplein 275
Den Haag 2545AA
NL
Els Borst-Eilersplein 275
Den Haag 2545AA
NL
Listed location countries
Age
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 b-lactams
6. Positive urine (> 103 CFU/ml) culture and/or blood culture with E. coli
susceptible to fosfomycin, ciprofloxacin and the empirical intravenous -lactam
treatment
7. Fulfilment 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 , All participants at the Haga Teaching
Hospital are also eligible for the pharmacokinetic part of the study.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004963-11-NL |
| CCMO | NL64395.098.18 |