Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia

NCT ID: NCT06695832

Last Updated: 2024-11-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 369 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2025-01-31

Brief Summary

Staphylococcus aureus bacteraemia is a frequent and life-threatening infection, despite current standard antibiotic monotherapy. This study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in patients with this serious infection. Two clinical trials suggested that adjunctive fosfomycin therapy might offer a clinical benefit in certain cases, but the results are inconclusive. We aim to analyse pooled data from these trials in order to identify subgroups of patients that might benefit most from this therapy.

Detailed Description

Background. Improving outcomes in patients with methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia (SAB) is a critical healthcare goal. Two recent randomised clinical trials (RCTs), the BACSARM trial and the SAFO trial, assessed the efficacy of fosfomycin as an adjunctive therapy for MRSA and MSSA SAB respectively. Although neither trial demonstrated statistically significant differences in their primary endpoints of treatment success and reduced mortality respectively, both studies observed lower rates of persistent bacteraemia in the fosfomycin groups.

Methods. We will perform a post-hoc analysis of pooled individual patient data from the BACSARM and SAFO trials, which will be referred to as the BACSAFO study. The primary exposure of interest is fosfomycin adjunctive therapy, and the primary outcome will be treatment success at 8 weeks, defined as the patient being alive, without signs of relapse, and showing improvement in clinical signs and symptoms. We will use both Bayesian and frequentist methodologies: the Bayesian analysis will use a hierarchical Bayesian log-binomial model, while the frequentist analysis will apply a hierarchical log-binomial model. In addition, we will investigate whether adjunctive fosfomycin is particularly beneficial in specific patient subgroups (created according to age, methicillin resistance, place of acquisition, and complicated bacteraemia status).

Discussion. The BACSAFO study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in SAB patients. Although previous trials have not demonstrated significant differences in the primary endpoints, the significant reductions in rates of persistent bacteraemia observed suggest that fosfomycin might offer a clinical benefit in certain cases. By analysing pooled data and attempting to identify subgroups that might benefit most, this study has the potential to refine treatment strategies and inform trial design and planning for future RCTs investigating combination antibiotic therapies for SAB.

Conditions

Staphylococcus Aureus Bacteremia

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: RETROSPECTIVE

Study Groups

Adjunctive fosfomycin

All patients receiving adjunctive fosfomycin (the combination therapy group).

No interventions assigned to this group

Standard antibiotic monotherapy group

All patients not receiving fosfomycin, i.e., those receiving daptomycin alone for MRSA bacteraemia or cloxacillin alone for MSSA bacteraemia.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• All patients included in the BACSARM and SAFO clinical trials.

Exclusion Criteria

• For both trials: polymicrobial bacteraemia, severe clinical status with expected survival < 24 hours, severe liver disease with Child-Pugh score class C, diagnosis of prosthetic infective endocarditis, allergy or known resistance to study drugs, pregnancy at the time of inclusion, inclusion in another clinical trial.
• For the BACSARM trial: diagnosis of MRSA pneumonia, prior history of eosinophilic pneumonia, use of additional antibiotic therapy with microbiological activity against MRSA.
• For the SAFO trial: prior history of myasthenia gravis, acute SARS-CoV2 infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut d'Investigació Biomèdica de Bellvitge

OTHER

Sponsor Role: collaborator

Hospital Universitari de Bellvitge

OTHER

Sponsor Role: lead

Responsible Party

Francesc Escrihuela-Vidal

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jordi Carratalà, Medical Doctor

Role: PRINCIPAL_INVESTIGATOR

Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain

Locations

The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity

Melbourne, Victoria, Australia

Institute of Health Policy, Management and Evaluation, University of Toronto

Toronto, Ontario, Canada

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Germans Trias i Pujol Research Institute and Hospital (IGTP)

Badalona, Catalonia, Spain

Hospital Clinic de Barcelona

Barcelona, Catalonia, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, Spain

Countries

Australia; Canada; Spain

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Other Identifiers

EOM033/24

Identifier Type: -

Identifier Source: org_study_id