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Completed

NCT Number: NCT07043673

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

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.

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Key information

Conditions

Plasma Concentration

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University Rouen Hospital

Rouen, 76031, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Measurement of plasma concentration of the free form of vancomycin

    Time frame: 24 hours after the start of continuous vancomycin infusion treatment

    The primary endpoint is determined by the measurement of the plasma concentration of the free form of vancomycin during the total plasma concentration measurement after at least 24 hours of continuous infusion treatment.

Secondary outcomes

  1. Measurement of the fraction of the non-protein-bound form of vancomycin in plasma

    Time frame: 24 hours

    The fraction unbound to plasma proteins (free form) of vancomycin will be determined by the ratio of the concentration of the free form to that of the total form, and expressed as a %.

  2. To determine the areas under the 24-hour curve (AUC24h) for total plasma protein-bound forms of vancomycin

    Time frame: 24 hours

    The area under the 24-hour plasma concentration curve (AUC24h) is calculated for vancomycin by the product of the plasma concentration times 24, due to continuous administration. It is expressed in mg.h/L.

  3. To compare the areas under the 24-hour curve (AUC24h) for total and non-plasma protein-bound forms of vancomycin

    Time frame: 24 hours

    The area under the 24-hour plasma concentration curve (AUC24h) is calculated for vancomycin by the product of the plasma concentration times 24, due to continuous administration. It is expressed in mg.h/L.

  4. To determine the areas under the 24-hour curve (AUC24h) for non-plasma protein-bound forms of vancomycin

    Time frame: 24 hours

    The area under the 24-hour plasma concentration curve (AUC24h) is calculated for vancomycin by the product of the plasma concentration times 24, due to continuous administration. It is expressed in mg.h/L.

  5. To assess the frequency of achieving vancomycin pharmacodynamic targets for its total plasma concentration

    Time frame: 24 hours

    The pharmacodynamic objective of vancomycin will be considered to be achieved when the AUC24h/MIC of the total form is greater than or equal to 400, corresponding to a total vancomycinemia greater than 17 mg/L, for the treatment of a Staphylococcus sp with a MIC of 1 mg/L

Sponsors and collaborators

Lead sponsor

University Hospital, Rouen

Other

Registry information

Official study title

Plasma Concentrations of the Non-protein-bound Form of Vancomycin in Intensive Care

Acronym: FREEVANCO

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Jun 29, 2025
Registry last updated
Jun 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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