Comparison of Two Dosage Adjustment Strategies of Vancomycin in Children (OPTIBAYE)

April 2, 2021 updated by: Assistance Publique - Hôpitaux de Paris

Vancomycin is the standard first-line treatment for MRSA infections and a first-line empiric therapy. The relationship between exposure to vancomycin and efficacy is admitted but because of an important intersubject variability, therapeutic exposure isn't usually achieved.

The primary aim of this randomized controlled trial is to evaluate a new early dosage adjustment strategy of vancomycin in children, comparing it to the usual treatment strategy.

Using a bayesian approach, the purpose is to achieve earlier a therapeutic and non-toxic exposure to vancomycin.

The primary hypothesis is that an early dosage adjustment strategy using a bayesian approach will allow patients to achieve the vancomycin pharmacological target faster than with the usual treatment strategy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction/ Clinical significance :

Staphylococcus aureus is a common cause of serious infections. Methicillin-resistant Staphylococcus aureus (MRSA) are one of the most common causes of nosocomial antibiotic resistant bacterial infections in the world. According to the last data from the European Antimicrobial Resistance Network, in 2014, 17,4 % of invasive staphylococcal infections are due to MRSA in France, with proportions of up to 56 % in some regions in the European Economic Area (EEA). In the United-States of America, MRSA reach 50 % of Staphylococcus isolates in some studies. Vancomycin is the standard first-line treatment for MRSA infections and a first-line empiric therapy.

To optimize good clinical outcomes for invasive MRSA infections using pharmacokinetics-pharmacodynamics of vancomycin, studies support targeting area under the curve (AUC) of the serum concentration versus time over 24 hours to minimum inhibitory concentration (MIC) ratio ≥ 400, which frequently correlates to a trough concentration of 15 - 20 mg/L when the MIC is 1 mg/L. Because of few consensus regarding the dosage to use and high intersubject variability, this pharmacological target is difficult to reach in children, which may lead to a delayed infection control and an increase of vancomycin toxicity-related side effects.

Aims :

The primary aim is to evaluate an early dosage adjustment strategy of vancomycin in children, comparing it to the usual treatment strategy.

Using a bayesian approach, the main purpose is to achieve earlier a therapeutic and non-toxic exposure to vancomycin.

The secondary aims are to compare with the usual treatment strategy 1) the proportion of subjects with vancomycin serum concentration within the concentration targets at the 24th hour of treatment, and 2) the clinical (in terms of fever), biological (in terms of CRP) and bacteriological (in terms of blood culture) efficacy of this early dosage adjustment strategy of vancomycin.

Hypothesis :

This study hypothesizes that early dosage adjustment strategy of vancomycin using a bayesian approach will be superior to usual treatment strategy in achieving the pharmacological target of vancomycin at the 24th hour of treatment in children.

Methodology :

As part of routine care, a prospective open-label randomized controlled trial will be conducted in a major paediatric hospital in Paris, France. Subjects will be divided into two arms. Each arm will contain 50 subjects.

For subjects of the Modeling arm, drug concentration will be measured at the 3rd hour of treatment and dosage adjustment will be done at the 6th hour of treatment using a bayesian approach. Vancomycin serum concentration will be then measured at the 24th hour of treatment.

Subjects of the control arm will receive the usual treatment strategy. Vancomycin serum concentration will be measured at the 24th hour of treatment.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Hôpital Necker-Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 16 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Children aged 1 months to 16 years
  • Children for whom a vancomycin treatment is started in the hospital Necker-Enfants Malades in Paris, France
  • No objection of parents and of the child himself if he is able to express it.

Exclusion Criteria:

  • Patients undergoing hemodialysis
  • Patients undergoing peritoneal dialysis
  • Newborns less than 1 months old
  • Adolescents more than 16 years old and adults

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Modeling arm
Early vancomycin monitoring and bayesian dosage adjustment
Other: Early vancomycin monitoring and bayesian dosage adjustment
Measure of vancomycin serum concentration at the 3rd hour of treatment and adjustment of vancomycin dosage at the 6th hour of treatment using a bayesian approach. Then measure of vancomycin serum concentration at the 24th hour of treatment.
Sham Comparator: Control arm
Usual vancomycin dose and monitoring strategy
Other: usual vancomycin dose and monitoring strategy
Vancomycin serum concentration will be measured at the 24th hour of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of subjects with vancomycin AUC/MIC ≥ 400 and serum trough concentration ≤ 20 mg/L
Time Frame: 24th hour of treatment
24th hour of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Jean-Marc TRELUYER, MD, PhD, Hôpital Necker-Enfants Malades

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2016

Primary Completion (Actual)

February 15, 2017

Study Completion (Actual)

February 15, 2017

Study Registration Dates

First Submitted

February 24, 2016

First Submitted That Met QC Criteria

February 24, 2016

First Posted (Estimate)

February 29, 2016

Study Record Updates

Last Update Posted (Actual)

April 5, 2021

Last Update Submitted That Met QC Criteria

April 2, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-A01545-44

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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