Overview
Efficacy of Cloxacillin and Fosfomycin Combination Versus Cloxacillin Monotherapy in Patients With MSSA Bacteremia
Status:
Recruiting
Recruiting
Trial end date:
2022-12-31
2022-12-31
Target enrollment:
0
0
Participant gender:
All
All
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 4Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Institut d'Investigació Biomèdica de Bellvitge
Miquel PujolCollaborators:
Institut d'Investigació Biomèdica de Bellvitge
Instituto de Salud Carlos IIITreatments:
Cloxacillin
Fosfomycin
Methicillin
Criteria
Inclusion Criteria:- Subjects, aged ≥ 18 years;
- MSSA bacteraemia: ≥ 1 positive blood culture(s) for MSSA in the first 72 h up to
randomisation in patients with clinical suspicion of infection;
- Written informed consent of the participant or the legal representative.
Exclusion Criteria:
- Severe clinical status with expected death <48h.
- Severe hepatic cirrhosis (Child-Pugh C).
- Moderate-severe cardiac chronic failure (NYHA III-IV).
- Prosthetic endocarditis (need for concomitant antibiotic therapy active against S.
aureus together with the study antibiotics for the first 7 days of the study).
- No pre-existing evidence of S. aureus fosfomycin non-susceptibility.
- Known hypersensitivity to cloxacillin or fosfomycin.
- Polymicrobial bacteraemia with more than one microorganism in blood cultures.
- A positive pregnancy test or pregnancy or lactation at the time of inclusion.
- Miastenia gravis.
- Participation in another clinical trial.
- Previous participation in the present clinical trial.
- Acute SARS-CoV2 infection.