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

Primary Purpose

Methicillin-resistant Staphylococcal Infections

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Early vancomycin monitoring and bayesian dosage adjustment
usual vancomycin dose and monitoring strategy
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Methicillin-resistant Staphylococcal Infections focused on measuring Vancomycin, Children, Infection, Antibiotic, Methicillin-resistant Staphylococcus aureus (MRSA), Population-based pharmacokinetic modeling, Pharmacokinetics, Pharmacodynamics, Bayesian approach, Therapeutic drug monitoring

Eligibility Criteria

1 Month - 16 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Necker-Enfants Malades

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Modeling arm

Control arm

Arm Description

Early vancomycin monitoring and bayesian dosage adjustment

Usual vancomycin dose and monitoring strategy

Outcomes

Primary Outcome Measures

Proportion of subjects with vancomycin AUC/MIC ≥ 400 and serum trough concentration ≤ 20 mg/L

Secondary Outcome Measures

Full Information

First Posted
February 24, 2016
Last Updated
April 2, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT02694458
Brief Title
Comparison of Two Dosage Adjustment Strategies of Vancomycin in Children
Acronym
OPTIBAYE
Official Title
Comparison of Two Dosage Adjustment Strategies of Vancomycin in Children
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
February 23, 2016 (Actual)
Primary Completion Date
February 15, 2017 (Actual)
Study Completion Date
February 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Methicillin-resistant Staphylococcal Infections
Keywords
Vancomycin, Children, Infection, Antibiotic, Methicillin-resistant Staphylococcus aureus (MRSA), Population-based pharmacokinetic modeling, Pharmacokinetics, Pharmacodynamics, Bayesian approach, Therapeutic drug monitoring

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Modeling arm
Arm Type
Experimental
Arm Description
Early vancomycin monitoring and bayesian dosage adjustment
Arm Title
Control arm
Arm Type
Sham Comparator
Arm Description
Usual vancomycin dose and monitoring strategy
Intervention Type
Other
Intervention Name(s)
Early vancomycin monitoring and bayesian dosage adjustment
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
usual vancomycin dose and monitoring strategy
Intervention Description
Vancomycin serum concentration will be measured at the 24th hour of treatment.
Primary Outcome Measure Information:
Title
Proportion of subjects with vancomycin AUC/MIC ≥ 400 and serum trough concentration ≤ 20 mg/L
Time Frame
24th hour of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Marc TRELUYER, MD, PhD
Organizational Affiliation
Hôpital Necker-Enfants Malades
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23340565
Citation
Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, Cho S, Natale S, Bui I, Tran TM, Capparelli EV. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013 Apr;32(4):e155-63. doi: 10.1097/INF.0b013e318286378e.
Results Reference
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PubMed Identifier
21208910
Citation
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4. Erratum In: Clin Infect Dis. 2011 Aug 1;53(3):319.
Results Reference
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PubMed Identifier
25548398
Citation
Hoang J, Dersch-Mills D, Bresee L, Kraft T, Vanderkooi OG. Achieving therapeutic vancomycin levels in pediatric patients. Can J Hosp Pharm. 2014 Nov;67(6):416-22. doi: 10.4212/cjhp.v67i6.1403.
Results Reference
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Comparison of Two Dosage Adjustment Strategies of Vancomycin in Children

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