An interventional study of Linezolid 600 mg and Placebo in Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia), sponsored by University Hospital, Basel, Switzerland. Recruiting at 12 sites in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-13.
Sponsored by University Hospital, Basel, Switzerland · Not applicable, Interventional, and Treatment
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.
Staphylococcus aureus (S. aureus) is one of the deadliest bacterial pathogens, especially in high-income countries, and causes bloodstream infections (bacteraemia) in 20-30 per 100,000 people annually. Despite widely available antibiotic treatments, the 90-day mortality rate remains high at 20-30%, and complications such as organ damage, relapses, and long-term impairment affect many survivors. Existing treatments have failed to improve survival rates highlighting the urgent need for novel therapeutic strategies.
Virulence factors produced by S. aureus facilitate bacterial persistence and spread, and tissue damage. Preclinical research suggests that inhibiting the production of virulence factors may improve patient outcomes. While some clinical guidelines recommend this approach for toxin-mediated infections, randomized controlled trials (RCTs) evaluating this approach in S. aureus bacteraemia have not yet been conducted.
Linezolid, an antibiotic commonly used for pneumonia and complicated skin and soft-tissue infections, has shown strong inhibition of the expression of S. aureus virulence factors in preclinical studies. Studies in animal models demonstrated that linezolid, when combined with other antibiotics, enhances treatment efficacy and reduces bacterial toxin production. Observational studies suggest that early initiation of linezolid may lead to better patient outcomes, but no RCT has tested this approach in S. aureus bacteraemia.
This placebo-controlled trial will evaluate whether adding a 5-day course of linezolid to standard antibiotic therapy improves clinical outcomes in patients with S. aureus bacteraemia.
297 studies on the registry are indexed under Bacteremia; 51 are open to participants now.
This study's planned enrollment of 606 is above the median of 156 across 156 interventional studies indexed under Bacteremia.
Browse Bacteremia studies →University Hospital, Basel, Switzerland is the lead sponsor of 990 studies on the registry; 189 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
600mg twice a day for 5 days (in addition to the standard antibiotic treatment)
Drug: Linezolid 600 mg
oral placebo tablets twice a day for 5 days (in addition to the standard antibiotic treatment)
Drug: Placebo
linezolid 600 mg tablets (twice a day for 5 days)
Placebo tablets (twice a day for 5 days)
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.
Time frame: From randomisation (day 1) until day 90
All-cause mortality
Proportion of patients who died from any cause during the duration of the study.
Time frame: From randomisation (day 1) until day 90
Time to death
Time frame: From randomisation (day 1) until day 90
Level of function
Proportion of participants back to their usual level of function prior to the infection.
Time frame: From randomisation (day 1) until day 90
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.
Time frame: From day 14 to day 90 (randomisation = day 1)
Number of participants with early microbiological failure leading to treatment change
Any positive sterile site culture with S. aureus between 5 and 13 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.
Time frame: From day 5 to day 13 (randomisation = day 1)
Number of participants with clinical failure leading to treatment change
Newly identified focus of S. aureus between 14 and 90 days after randomisation as determined by the site investigator (or delegated physician) that leads to a change in treatment. This can incorporate clinical, radiological, microbiological and pathological findings.
Time frame: From day 14 to day 90 (randomisation = day 1)
Number of participants with early clinical failure leading to treatment change
Newly identified focus of S. aureus between 5 and 13 days after randomisation as determined by the site investigator (or delegated physician) that leads to a change in treatment. This can incorporate clinical, radiological, microbiological and pathological findings.
Time frame: From day 5 to day 13 (randomisation = day 1)
Hospital length of stay
Duration of the index acute hospital stay from randomisation until the day of hospital discharge. Transfers to another acute care hospital for continuation of acute treatment will be included in the assessment of hospital length of stay. Days after transfer to rehabilitation centres or switch to outpatient parenteral ambulatory treatment will not be included in the acute hospital stay.
Time frame: From randomisation (day 1) until day 90
Time to being discharged alive
For participants who die during the hospitalisation, 90 days will be recorded.
Time frame: From randomisation (day 1) until day 90
Days alive without being on the Intensive Care Unit (ICU)
Number of days a participant is alive and not hospitalised in the Intensive Care Unit.
Time frame: From randomisation (day 1) until day 90
Days alive without antibiotics
Number of days a participant is alive and not on any antibiotics.
Time frame: From randomisation (day 1) until day 90
Mental health
Mental health assessed by patient-reported outcome using Short Form-36 (SF-36) questionnaire. The SF-36 questionnaire score ranges from 0 to 100, with higher scores indicating better health.
Time frame: At day 90 (randomisation = day 1)
Physical health
Physical health assessed by patient-reported outcome using SF-36 questionnaire. The SF-36 questionnaire score ranges from 0 to 100, with higher scores indicating better health.
Time frame: At day 90 (randomisation = day 1)
Number of participants with persistent bacteraemia
S. aureus-positive blood culture on day 5 (±1 day) after randomisation. If day 2 or day 3 blood cultures are negative and no subsequent blood cultures are performed, the day 5 blood culture is presumed to be negative.
Time frame: At day 5 (randomisation = day 1)
Two or more systemic inflammatory response syndrome (SIRS) criteria fulfilled
SIRS criteria: * Abnormal body temperature (\<36°C or \>38°C) * tachypnoea or mechanical ventilation (RR\>20 breaths per minute) * tachycardia (HR \>90 beats per minute in an adult * abnormal leukocyte count (from routine blood sampling on day 5 ±1 day, defined as \>12.0 x 10\^9/L or \<4.0 x 10\^9/L or \>10% of immature (band) forms)
Time frame: At day 5 (randomisation = day 1)
Change in C-reactive protein (CRP)
Day 1 CRP means any blood CRP measurement taken on randomisation day 1 or the calendar day prior to randomisation. If there is more than one measurement, the value recorded is the one taken closest before randomisation.
Time frame: From randomisation (day 1) until day 5
Development of new antibiotic drug resistance in Staphylococcus aureus
Any new resistance absent in the S. aureus from the initial blood culture and detected in any S. aureus cultured after the start of the intervention.
Time frame: From randomisation (day 1) until day 90
Adverse events leading to study drug discontinuation
Any adverse event (irrespective of grade) leading to study drug discontinuation as documented by the treating physician.
Time frame: From randomisation (day 1) until day 5
Serious adverse reactions until day 90
Any serious adverse event will be reported to the study-site principal investigator, who then assesses whether there is a reasonable causal relationship with the investigational medicinal product.
Time frame: From randomisation (day 1) until day 90
Clinical signs of serotonin toxicity
Assessed using the Hunter Serotonin Toxicity Criteria.
Time frame: From randomisation (day 1) until day 7
Laboratory signs of myelosuppression
Laboratory confirmation of thrombocytopenia, anaemia, or leukopenia.
Time frame: From randomisation (day 1) until day 7
Evidence of hyperlactatemia
In case of clinical suspicion of hyperlactatemia, lactate levels will be measured and compared to specific laboratory-defined reference ranges. For increased lactate levels, the causality with the study treatment will be assessed.
Time frame: From randomisation (day 1) until day 7
Acute kidney injury
Assessed on day 5 and, if participant remains hospitalised, on day 14, using the Kidney Disease Improving Global Outcomes (KDIGO) definition.
Time frame: From randomisation until day 14
Number of participants with Clostridioides difficile (C. difficile)-associated diarrhoea
This means a stool submitted to a clinical laboratory has tested positive for C. difficile toxin or toxin gene.
Time frame: From randomisation (day 1) until day 90
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).
Time frame: At day 5 (day of randomisation = day 1)
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.
Time frame: From randomisation (day 1) until day 90 or until the date of the participant's first blood culture negative for S. aureus, whichever came first.
Plan to share: Yes — After publication of the main results, the full dataset will be submitted to the Data Access Committee of the Faculty of Medicine (MF-DAC) at the University of Basel. Other researchers interested in using the study data may contact the independent MF-DAC of the University of Basel to request access.
Supporting information: Study protocol, Statistical analysis plan
Time frame: A detailed statistical analysis plan will be finalised before database lock. The statistical analysis plan will be made publicly available on clinicaltrials.gov.
Started Oct 2025 (actual). Primary completion is estimated for Oct 2028, 36 months after the start.
Of 34 non-industry interventional studies with no phase under Bacteremia, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 64. This study's planned 36 months is close to that.
Counting every sponsor, half of 35 studies reached it within 34 months; a quarter within 13 and three quarters within 64.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Linezolid
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