Efficacy of Cloxacillin and Fosfomycin Combination Versus Cloxacillin Monotherapy in Patients With MSSA Bacteremia
Status:
Recruiting
Trial end date:
2022-12-31
Target enrollment:
Participant gender:
Summary
Background: Despite management improvement in lasts years, S.aureus bacteremia leads to high
morbidity and mortality. For over 50 years, methicillin-susceptible S.aureus (MSSA)
bacteremia standard treatment was cloxacillin. Previous studies using different therapies and
combination treatment fall to improve survival in these patients.
Aim: to demonstrate the efficacy of the cloxacillin and fosfomycin combination administered
during the first week of treatment, compared with cloxacillin monotherapy in patients with
MSSA bacteremia in treatment success. Methods: A multicentre, superiority, open-label,
randomized, phase IV-III, two-armed parallel (1:1) groups clinical trial. Adult patients with
MSSA bacteremia will be randomized to Combination therapy group: patients will receive
intravenous cloxacillin 2g/4h and fosfomycin 3 g/6h for the duration of 7 days treatment, or
Standard therapy group: patients will receive intravenous cloxacillin 2g/4h for the duration
of 7 days IV treatment. After the first week, antibiotic treatment and duration will be
decided by responsible clinician following clinical practice.
The primary endpoint is the treatment success measured at day 7 of treatment; a composite
endpoint defined by all of the following criteria met after randomization: patient alive at
day 7 AND stable or improved quick SOFA score (compared with baseline) at day 7 AND fever
resolved at day 7 AND negative blood cultures for S. aureus at day 7.
In case of achieving statistical differences in the primary endpoint, investigators will
perform a hierarchical analysis of the treatment success at Test of Cure visit (TOC, 12 weeks
after randomization), defined by the presence of all of the following: patient alive at TOC
AND no evidence of microbiological treatment failure defined as isolation of S. aureus from
blood culture or other sterile site from day 8 after randomization until TOC.
Investigators have assumed a 74% of treatment success in monotherapy group. Accepting an
alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 183 subjects are necessary in
first group and 183 in the second to find a statistically significant difference of 12%. It
has been anticipated a drop-out rate of 5%.
Discussion: Randomized studies assessing efficacy of different treatment in MSSA bacteremia
are lacking. This study could help to improve knowledge about MSSA bacteremia and whether
combined treatment with cloxacillin and fosfomycin could improve outcomes compared with
standard treatment.
Phase:
Phase 4
Details
Lead Sponsor:
Institut d'Investigació Biomèdica de Bellvitge Miquel Pujol
Collaborators:
Institut d'Investigació Biomèdica de Bellvitge Instituto de Salud Carlos III