EXtended Use of FOsfomycin for the Treatment of CYstitis in Primary Care
Status:
Terminated
Trial end date:
2022-02-14
Target enrollment:
Participant gender:
Summary
Cystitis is the most frequent reason for women to visit their general practitioner. More than
600.000 women suffer from urinary tract infections in The Netherlands each year. Currently,
the 1st choice treatment for uncomplicated cystitis is nitrofurantoin (NIT) for 5 days. The
second choice is 3 gram fosfomycin-trometamol (FT) in a single dose. FT is increasingly
prescribed because it has few side-effects and it has a patient-friendly dosing scheme.
Previous research did not show significant difference in efficacy between fosfomycin and
nitrofurantoin, but a clinical trial from 2018 claims a single dose of FT might be inferior
to 5 days of nitrofurantoin. Pharmacodynamic and pharmacokinetic research suggests that a
single dose of FT may be insufficient to cure cystitis. Overall, it remains unknown whether a
single gift of FT is as efficacious as 5 days of nitrofurantoin for uncomplicated cystitis
with regard to clinical cure and if an additional gift of FT would overcome this. A clinical
trial is therefore warranted.
Objective: To investigate the comparative effectiveness and side-effects of 5 days of
nitrofurantoin, single dose FT, and extended use of FT in uncomplicated cystitis in primary
care.
Study design: An open-label randomized non-inferiority / superiority study with 3 arms.
Study population: 777 non-pregnant women with symptoms of uncomplicated cystitis, with 259
subjects in each study arm.
Intervention: (A) FT in a single dose of 3000mg on day 1; (B) extended dosing of 3000mg FT on
day 1 and 3 (C) nitrofurantoin 100mg bid (slow release) for 5 days.
Main study parameters/endpoints: primary: days of absence of cystitis symptoms within 28
days. Secondary: clinical failure on day 28, microbiological failure on day 28, incidence of
side-effects, cost-effectiveness Burden and risks associated with participation, benefit and
group relatedness: A potential risk of participation is that the treatment arm to which the
patient is allocated is either less efficacious, has more adverse events or higher recurrence
rate than the other treatment arms. However, NIT and FT are both frequently used for urinary
tract infections and considered safe and effective compounds for uncomplicated cystitis.
According to previous studies, a second dose of FT is well tolerated. The potential risks of
participation on severe adverse events is expected to be negligible as the risk of severe
clinical failure after cystitis treatment is only 1% according to previous studies and
differences between NIT and FT have not been observed previously. A potential benefit of
participating to this study is that a more patient friendly treatment scheme is equally
effective. For future patients the guidelines could be improved and become more
patient-friendly. The burden of participation is considered low. Study participants need to
complete a short daily questionnaire on a mobile application up to 28 days.
Phase:
Phase 3
Details
Lead Sponsor:
MJM Bonten
Collaborators:
Saltro ZonMw: The Netherlands Organisation for Health Research and Development