Plasma Concentrations of the Non-protein-bound Form of Vancomycin

NCT ID: NCT07043673

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 77 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-17
• Study Completion Date: 2025-03-01

Brief Summary

In routine practice, the use of vancomycin must be accompanied by plasma concentration monitoring to ensure that pharmacodynamic targets are met and that plasma concentrations are not in toxic ranges.

Because vancomycin has high plasma protein binding and a free fraction exhibits marked inter-individual variability, this variability is increased in intensive care, monitoring is all the more imperative.

The factors influencing the concentration and/or free fraction of vancomycin are numerous and vary from one study to another. The striking fact of this work is that the link between the concentration of the total form and the concentration of the free form has not been established.

However, only plasma measurements of the total form of vancomycin are currently available to clinicians in routine practice, while only the free fraction is biologically active, responsible for its efficacy, but also for its toxicity in the event of an overdose. This paradox is widely highlighted by authors who have studied the free fraction of vancomycin, emphasizing the importance of continuing scientific research on this subject. Moreover, these studies are few in number, particularly in intensive care units, and their sample size is small, and they present biases, particularly those related to their essentially retrospective nature.

The failure to consider the free concentration of vancomycin in the therapeutic monitoring strategy is primarily explained by the fact that clinicians do not have access to plasma concentrations of the free form of drugs in routine practice. Thus, the guidelines do not include pharmacodynamic targets for the free concentration, due to the lack of scientific data on the subject.

Detailed Description

Since 2019, the Rouen University Hospital Pharmacology Laboratory has been measuring the non-protein-bound plasma concentrations of certain beta-lactam antibiotics. The analyzed sample comes from ultrafiltration of the plasma sample, a pre-analytical technique used in several studies on the free form of vancomycin. Access to this new technique at Rouen University Hospital gives us the opportunity to study free vancomycin concentrations in ICU patients.

This study therefore aims to investigate free vancomycin plasma concentrations in patients admitted to the ICU treated for suspected or proven Gram-positive cocci infection, and for whom a dosage has been prescribed as part of routine practice.

This prospective study aims to specifically analyze the concentration of the free form of vancomycin, but also to determine whether certain clinical or biological factors could predict this concentration. The long-term objective would be to be able to better individualize dosage regimens for vancomycin, a molecule with high inter-individual variability in intensive care patients, with the aim of reducing both underdoses, which are responsible for therapeutic failures, and overdoses, which are responsible for toxicity.

Conditions

Plasma Concentration

Keywords

vancomycine

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Vancomycin plasma dosage group

Any intensive care patient at the Rouen University Hospital undergoing a plasma vancomycin dosage carried out as part of routine care for a suspected or proven Gram + Cocci infection

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Adult patient hospitalized in intensive care,
• Treated with vancomycin for a proven or suspected Gram-positive cocci infection,
• For whom a plasma vancomycin dose has been prescribed
• Patient who has been informed and has expressed verbal non-opposition. If the patient is unable to express their non-opposition (emergency situations), non-opposition must be obtained from the patient's representative, their trusted person, or, failing that, a relative.

Exclusion Criteria

• Objection from the patient or their relatives
• Discontinuous administration of vancomycin
• Total plasma vancomycin levels measured 5 days or more prior to inclusion, with the plasma sample being stored in the laboratory for only 5 days, as is standard practice.
• Individuals not covered by a social security scheme
• Failure to perform the prescribed vancomycin dosage: discontinuation of vancomycin, death, etc.
• Vancomycin serum sample taken before the 24th hour, including the loading dose.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe PG GOUIN, Professor

Role: STUDY_DIRECTOR

University Hospital, Rouen

Locations

University Rouen Hospital

Rouen, , France

Countries

France

Other Identifiers

N° IDRCB : 2022-A00706-37

Identifier Type: OTHER

Identifier Source: secondary_id

2022/058/OB

Identifier Type: -

Identifier Source: org_study_id