Linezolid or Vancomycin Surgical Site Infection Prophylaxis

NCT05571722 | Recruiting Phase 4 DMC

• 1 other identifier: RCAPHM22_0233
• Study Type: interventional
• Target: 1,160
• Locations: 1 country
• Sites: 1

Brief Summary

Anesthesia and surgical guidelines recommend the administration of a surgical antibiotic prophylaxis for patients undergoing "clean" surgery. The prescribed antibiotic should target the bacteria most commonly found in surgical site infections (SSIs) and the duration of administration should not exceed 24 hours to minimize the ecological risk of bacterial resistance emergence. Guidelines provide a framework for the administration of surgical antibiotic prophylaxis but their effectiveness is regularly re-evaluated by measuring the rates of SSIs and the microorganisms responsible for infectious complications after surgery. The majority of interventions required the use of first or second generation cephalosporins as surgical antibiotic prophylaxis. For patients with allergy to beta-lactams, clindamycin and vancomycin are proposed as alternatives. In the patients with methicillin-resistant S. aureus (MRSA) colonization or if those at risk of developing MRSA-associated SSI (hospital ecology, previous antibiotic treatment), only vancomycin is recommended. Vancomycin pharmacokinetics and pharmacodynamics is complex and its tissue absorption varies according to the level of tissue inflammation. This is a difficult molecule to handle, exclusively administered via intravenous route. Linezolid is a synthetic antibiotic from the oxazolidinone class. By binding to the rRNA on the 30S and 50S ribosomal subunits, it inhibits the bacterial synthesis. It is therefore a bacteriostatic antibiotic approved for the treatment of both methicillin susceptible S. aureus (MSSA) and MRSA infections. It also covers a broad spectrum of Gram positive bacteria. Its pharmacokinetics allows rapid intravenous infusion, with rapid penetration into bone and soft tissue of the surgical site during hip surgery. A large Cochrane meta-analysis reported that linezolid was superior to vancomycin in skin infections, including MRSA infections, albeit with low quality evidence. We therefore hypothesized that linezolid can be used instead of vancomycin for beta-lactam allergic patients and patients at risk of MRSA-associated SSI in general surgery.

Conditions

Antibiotic Prophylaxis; General Surgery

Outcome Measures

Primary Outcomes (1)

• Comparaison of the rates of SSIs in patients receiving vancomycin 30 mg/kg versus patients receiving linezolid 1200 mg as surgical antibiotic prophylaxis for all types of surgery

  The SSIs are defined according to the standardized and validated Centers for Disease Control (CDC) criteria, including three levels of infection (superficial, deep, organ or space) (10). These definitions were endorsed by Santé Publique France and are used by the ISO-Raisin Network for the surveillance of nosocomial infections.

  Day 30 after surgery

Secondary Outcomes (9)

• Assessment of SSIs rates in all patients after 365 days

  365 after surgery

• Comparaison of treatment compliance

  Day-365

• Number of days from hospital admission to surgery, from surgery to discharge, from inclusion to discharge

  Day-365

• Mortality rates In-hospital, at day-30, at day-90 and at day-365;

  day-30, at day-90 and at day-365

• Antibiotic-free days during the 30-days following surgery

  Day-30

Study Arms (2)

Control group: Vancomycin

ACTIVE COMPARATOR

Patients receive a dose of 30 mg/kg of vancomycin (2 hours infusion) starting 2.5 hours before the scheduled time of surgical incision as defined in the French guidelines.

Drug: Vancomycin Injection

Experimental group: linezolid

EXPERIMENTAL

Patients receive a dose of 1200 mg of linezolid (30 minutes infusion) 30 minutes before the scheduled time of surgical incision.

Drug: Linezolid Injection

Interventions

Vancomycin Injection DRUG

Patients receive a dose of 30 mg/kg of vancomycin (2 hours infusion) starting 2.5 hours before the scheduled time of surgical incision as defined in the French guidelines.

Control group: Vancomycin

Linezolid Injection DRUG

Patients receive a dose of 1200 mg of linezolid (30 minutes infusion) 30 minutes before the scheduled time of surgical incision.

Experimental group: linezolid

Eligibility Criteria

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

You may qualify if:

• Patients undergoing any elective surgery for which vancomycin is recommended in the guidelines as an alternative to beta-lactams including: neurosurgery, cardiac surgery, orthopedic surgery, vascular surgery, penile and testicular surgery, gastric banding procedure in digestive surgery.
• Age ≥ 18 years-old;
• Known allergy to beta-lactams AND/OR suspected or proven MRSA colonization. Proven MRSA colonization is defined as a positive patient sample (any type of swab or biological fluid) for MRSA within 3 months prior to surgery. MRSA colonization is suspected when the patient undergoing surgery has received antibiotic treatment within 3 months prior to surgery or is undergoing re-intervention more than 5 days after the first surgery. MRSA is defined as a strain of Staphylococcus aureus resistant to oxacillin or cefoxitin, predicting non-susceptibility to all classes of beta-lactam antimicrobials (except anti-MRSA cephalosporins) (6). In contrast, MSSA is defined as an oxacillin sensitive strain of Staphylococcus aureus;
• Informed consent of the patient;
• Affiliated to a social security system or equivalent.

You may not qualify if:

• Surgery for suspected or proven SSI (definition of SSI provided on chapter 3.6.1 Primary endpoint as defined by (5, 7)) according to international definitions;
• Obesity defined by a body mass index (BMI) \> 35 kg/m2 or a body weight \> 100 kg;
• Chronic kidney disease defined as glomerular filtration rate (GFR) \< 60 ml/min per 1.73m2;
• Known allergy to linezolid or vancomycin;
• Hematologic malignancy;
• Declared pregnancy or breastfeeding;
• Patient under legal protection regime for adults;
• Patient denying consent;
• Patient already included in LOVip for a previous surgery.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Anesthésie Réanimation - Hôpital Nord (AP-HM)

Marseille, 13015, France

RECRUITING

MeSH Terms

Interventions

Vancomycin; Linezolid

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• François CREMIEUX

  Assistance Publique Hopitaux De Marseille

  STUDY DIRECTOR

Central Study Contacts

Marc Leone, MD

CONTACT

0491968655; Marc.LEONE@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The treatment scheme of the study does not allow for double-blinded manipulations. Postoperative evaluations and measurements will be performed in a blinded fashion by an investigator different from the physician who managed the patient in the operating room: SSI rates, adverse events, and length of stay. Statistical analyses will be performed in a blinded fashion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-blind randomized controlled trial

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 7, 2022
• Study Start: November 12, 2024
• Primary Completion (Estimated): December 3, 2028
• Study Completion (Estimated): December 3, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)