About this trial
The aim of the study is to assess whether targeting virulence factors by administering linezolid in addition to standard antibiotic treatment improves outcomes in patients with Staphylococcus aureus bacteraemia.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Staphylococcus aureus (S. aureus) grown from at least one blood culture
Hospitalised at a participating centre
≥18 years old
Written informed consent or fulfilling criteria for an emergency exception from informed consent requirements
Disqualifiers
Administration of the initial drug treatment not feasible within 72 hours since the collection of the first positive blood culture with S. aureus
Documented history of positive blood cultures for S. aureus occurring between 72 hours and 180 days prior to the eligibility assessment
Necrotising fasciitis
Currently receiving linezolid or clindamycin
Trial design
Parallel
Treatments tested in this trial
Linezolid 600 mg
Druglinezolid 600 mg tablets (twice a day for 5 days)
Placebo
DrugPlacebo tablets (twice a day for 5 days)
Treatment groups
Trial outcomes
Primary outcomes
Desirability of Outcome Ranking (DOOR)
The hierarchical composite endpoint DOOR will be calculated based on the following 4 criteria: 1. Alive at 90 days 2. Return to usual level of function by day 90 3. None of the following complications: Microbiological or clinical failure leading to treatment change; Serious adverse reaction; Adverse event leading to study drug discontinuation 4. Hospital length of stay The primary outcome will be expressed as the win ratio, i.e., the ratio of the number of times that participants in the intervention group have a lower DOOR compared to those in the control group. In this study, a pairwise comparison is used, i.e., every participant in the linezolid group is compared with every participant in the control group. When comparing two participants, the winner will be determined by the first component of the DOOR in which the two participants differ, the only exceptions being ties when both participants die or if they do not die but have the same length of hospitalisation.
Secondary outcomes
All-cause mortality
Proportion of patients who died from any cause during the duration of the study.
Time to death
Level of function
Proportion of participants back to their usual level of function prior to the infection.
Number of participants with microbiological failure leading to treatment change
Any positive sterile site culture with Staphylococcus aureus (S. aureus) between 14 and 90 days after randomisation that leads to a change in treatment. A sterile site means any site of the body where microorganisms are usually absent, i.e. below the outer and inner colonised surfaces of the skin and mucous membranes. Positive sterile sites cultures include deep visceral and musculoskeletal abscesses obtained in a sterile manner.
Other outcomes
Linezolid trough plasma concentrations at day 4 or 5
Additional exploratory laboratory outcome for a subset of participants only in participating centres (results may be reported in a publication separate from the publication of the main study results).
Molecular mechanisms of S. aureus bacteraemia
Basic research on the location of S. aureus in human blood (extracellular or intracellular). This will be conducted in a sub-sample of participants consenting to additional blood sampling and published separately from the publication of the main study results.
Sponsors and contacts
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University Hospital, Basel, Switzerland
Lead sponsor
Swiss National Science Foundation
Collaborator