To evaluate if the combination of pivmecillinam and clavulanic acid (PAC) is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in patients with febrile UTI caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales (EPE).
A recent observational cohort study supports the notion that beta-lactams can be used with similar efficacy to fluoroquinolones as step down therapy in bacteremic E. coli UTI's. As such, pivmecillinam clavulanic acid (PAC) constitute an appealing per oral alternative, but the combination's safety and efficacy has not been evaluated in a clinical trial The aim of this trial is to investigate whether the PAC combination is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in treating EPE-causing febrile UTI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
330
1 tablet pivmecillinam 400 mg and 1 tablet Amoxicillin/clavulanic acid 875/125 mg, three times daily.
Ciprofloxacin 500 mg twice daily, trimethoprim/sulfamethoxazole 800 mg/160 mg twice daily or ertapenem 1 g once daily.
Helsingborg hospital
Helsingborg, Sweden
RECRUITINGKristianstad hospital
Kristianstad, Sweden
RECRUITINGSkåne University Hospital, Lund
Lund, Sweden
RECRUITINGClinical cure
Clinical cure defined as being alive with absence of fever (≥ 38.3 C) and resolution of, or return to non-infected baseline of, urinary tract symptoms (as defined in inclusion criteria) without additional antibiotic treatment (for UTI symptoms) based on fever control and a semi-structured interview at a live return visit to an independent physician (i.e. not previously involved in the care of the study participant) at an infectious disease clinic.
Time frame: Clinical cure 10 days (+/- 2 days)
To compare the recurrence prevalence of EPE (phenotypically same species) in urine cultures 10 +/- 2 days after antibiotic treatment between groups (i.e., microbiological cure).
Yes or no.
Time frame: Up to 28 days
To compare the prevalence of EPE or carbapenemase-producing bacteria in faecal cultures 10 +/- 2 days after antibiotic treatment between groups.
Yes or no.
Time frame: Up to 28 days
To compare participants' perception of treatment tolerability
Tolerability is measured on a 1-10 scale.
Time frame: 10 days
To compare the incidence of early study drug discontinuation between groups.
Yes or no.
Time frame: 10 days
To compare the incidence of additional antibiotic subscriptions (for UTI) within 28 days between groups.
Yes or no.
Time frame: 28 days
To compare re-admission to hospital (due to UTI-related symptoms) within 28 days between groups.
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Skåne University Hospital, Malmö
Malmo, Sweden
RECRUITINGVästmanland hospital Västerås
Västerås, Sweden
RECRUITINGYes or no.
Time frame: 28 days
To compare the incidence of drug-related serious adverse events (SAE) within 28 days between groups.
Yes or no.
Time frame: 28 days
To compare the all-cause mortality within 28 days between groups.
Yes or no.
Time frame: 28 days