Linezolid Plus Standard of Care

NCT06958835 | Recruiting DMC

• 1 other identifier: 2025-00655; am23Khanna3
• Study Type: interventional
• Target: 606
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia)

Keywords

Virulence factors; Linezolid; Bloodstream Infection; Hierarchical composite endpoint; Staphylococcus aureus; Bacteremia; Bacteraemia; Methicillin-resistant Staphylococcus aureus (MRSA); Penicillin-susceptible Staphylococcus aureus (PSSA); Methicillin-susceptible Staphylococcus aureus (MSSA)

Outcome Measures

Primary Outcomes (1)

• 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.

  From randomisation (day 1) until day 90

Secondary Outcomes (24)

• All-cause mortality

  From randomisation (day 1) until day 90

• Time to death

  From randomisation (day 1) until day 90

• Level of function

  From randomisation (day 1) until day 90

• Number of participants with microbiological failure leading to treatment change

  From day 14 to day 90 (randomisation = day 1)

• Number of participants with early microbiological failure leading to treatment change

  From day 5 to day 13 (randomisation = day 1)

Other Outcomes (2)

• Linezolid trough plasma concentrations at day 4 or 5

  At day 5 (day of randomisation = day 1)

• Molecular mechanisms of S. aureus bacteraemia

  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.

Study Arms (2)

Linezolid

EXPERIMENTAL

600mg twice a day for 5 days (in addition to the standard antibiotic treatment)

Drug: Linezolid 600 mg

Placebo

PLACEBO COMPARATOR

oral placebo tablets twice a day for 5 days (in addition to the standard antibiotic treatment)

Drug: Placebo

Interventions

Linezolid 600 mg DRUG

linezolid 600 mg tablets (twice a day for 5 days)

Linezolid

Placebo DRUG

Placebo tablets (twice a day for 5 days)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Use of any monoamine oxidase A or B inhibitor within the last two weeks
• Known hypersensitivity to linezolid or any other ingredients of the study drugs
• Current severe thrombocytopenia (i.e. \<30 x 10\^9/L)
• Application of study drug not possible (per mouth or per gastric tube)
• Currently breastfeeding
• Local treating team believes that death is imminent and inevitable
• Patient is receiving end of life care and antibiotic treatment is not considered appropriate
• Local treating team believes that participation in the study is not in the best interest of the patient
• Any indication that the patient is unwilling to participate in the study including an advance directive stating such unwillingness

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (12)

Kantonsspital Aarau (KSA)

Aarau, Canton of Aargau, Switzerland

RECRUITING

St. Claraspital

Basel, Canton of Basel-City, Switzerland

RECRUITING

Hôpitaux universitaires de Genève (HUG)

Geneva, Canton of Geneva, Switzerland

NOT YET RECRUITING

Hôpital du Jura

Delémont, Canton of Jura, Switzerland

NOT YET RECRUITING

Centre hospitalier universitaire vaudois (CHUV)

Lausanne, Canton of Vaud, Switzerland

NOT YET RECRUITING

Kantonsspital Winterthur (KSW)

Winterthur, Canton of Zurich, Switzerland

NOT YET RECRUITING

Ente Ospedaliero Cantonale (EOC)

Lugano, Canton Ticino, Switzerland

RECRUITING

University Hospital Basel (USB)

Basel, 4031, Switzerland

RECRUITING

Inselspital Bern

Bern, Switzerland

NOT YET RECRUITING

HOCH Health Ostschweiz, Kantonsspital St.Gallen

Sankt Gallen, Switzerland

NOT YET RECRUITING

Stadtspital Zürich Triemli

Zurich, Switzerland

RECRUITING

Universitätsspital Zürich (USZ)

Zurich, Switzerland

RECRUITING

MeSH Terms

Conditions

Bacteremia; Sepsis; Staphylococcal Infections; Toxemia

Interventions

Linezolid

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Positive Bacterial Infections

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard Kühl, PD Dr. med.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

• Benjamin Speich, PD, PhD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

• Nina Khanna, Prof. Dr. med.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Kühl, PD Dr. med.

CONTACT

+41 61 328 66 61; richardalexander.kuehl@usb.ch

Natalie Rose, PhD

CONTACT

+41 61 328 35 54; natalie.rose@usb.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: May 6, 2025
• Study Start: October 6, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.

Locations

CH (12)