Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia (BACSAFO)

November 20, 2024 updated by: Francesc Escrihuela-Vidal, Hospital Universitari de Bellvitge

Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia: Protocol for a Pooled Post-hoc Analysis of Two Randomised Clinical Trials

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.

Study Overview

Status

Active, not recruiting

Conditions

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.

Study Type

Observational

Enrollment (Actual)

369

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity
  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Institute of Health Policy, Management and Evaluation, University of Toronto
  • Spain
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Hospital Universitari de Bellvitge
    • Catalunya
      • Badalona, Catalunya, Spain, 08916
        • Germans Trias i Pujol Research Institute and Hospital (IGTP)
      • Barcelona, Catalunya, Spain, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Catalunya, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

In the BACSARM trial, 155 adult patients with MRSA bacteraemia were randomised 1:1 to receive daptomycin in combination with fosfomycin or daptomycin alone. In the SAFO trial, 214 adult patients with MSSA bacteraemia were randomised 1:1 to receive cloxacillin in combination with fosfomycin or cloxacillin alone. As this is a pooled analysis of all SAB, all patients included in the intention-to-treat analysis of the BACSARM and SAFO trials will be included in the present study, regardless of their susceptibility to methicillin.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Adjunctive fosfomycin
All patients receiving adjunctive fosfomycin (the combination therapy 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment success at 8 weeks from the time of randomisation
Time Frame: 8 weeks from the time of randomisation

A composite outcome available from the information collected in both trials and based on the fulfilment of all the following criteria:

  • Alive at week 8 from the time of randomisation.
  • Absence of relapse within 8 weeks after randomisation, defined as isolation of S. aureus in blood cultures after the index blood cultures were cleared.
  • Improvement of clinical signs and symptoms as assessed by investigators of the BACSARM and SAFO trials at week 8 from the time of randomisation.
8 weeks from the time of randomisation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Persistent bacteraemia
Time Frame: At days 3 and 7 from the time of randomisation
Positive blood cultures for S. aureus at days 3 and 7 from the time of randomisation
At days 3 and 7 from the time of randomisation
Mortality at days 14, 30 and 60 from the time of randomisation
Time Frame: Days 14, 30 and 60 from the time of randomisation
Mortality at days 14, 30 and 60 from the time of randomisation
Days 14, 30 and 60 from the time of randomisation
Adverse events leading to treatment discontinuation
Time Frame: During the time that adjunctive fosfomycin therapy was administered
Adverse events leading to treatment discontinuation during adjunctive fosfomycin therapy
During the time that adjunctive fosfomycin therapy was administered

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitari de Bellvitge

Collaborators

Institut d'Investigació Biomèdica de Bellvitge

Investigators

  • Principal Investigator: Jordi Carratalà, Medical Doctor, Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

January 31, 2025

Study Completion (Estimated)

January 31, 2025

Study Registration Dates

First Submitted

November 18, 2024

First Submitted That Met QC Criteria

November 18, 2024

First Posted (Actual)

November 19, 2024

Study Record Updates

Last Update Posted (Estimated)

November 22, 2024

Last Update Submitted That Met QC Criteria

November 20, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EOM033/24

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual data cannot be shared because of privacy restrictions. Raw anonymised data relating to primary and secondary outcomes and safety can be shared upon request to researchers who provide a methodologically reasonable proposal. The request for data can be sent to the corresponding author (J.C.). A period of 18 months after publication of the main study results should elapse before requests are made, so as to allow authors to publish substudies. Interested researchers must obtain the approval of the Bellvitge University Hospital Ethics Committee.

IPD Sharing Time Frame

A period of 18 months after publication of the main study results should elapse before requests are made.

IPD Sharing Access Criteria

Researchers who request to BACSAFO principal investigators providing a methodologically reasonable proposal. Interested researchers must obtain the approval of the Bellvitge University Hospital Ethics Committee.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Staphylococcus Aureus Bacteremia

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burkina Faso

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe