Comparison of Two Dosage Adjustment Strategies of Vancomycin in Children (OPTIBAYE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02694458|
Recruitment Status : Unknown
Verified March 2016 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was: Active, not recruiting
First Posted : February 29, 2016
Last Update Posted : March 1, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Methicillin-resistant Staphylococcal Infections||Other: Early vancomycin monitoring and bayesian dosage adjustment Other: usual vancomycin dose and monitoring strategy||Not Applicable|
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.
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.
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.
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 (Clinical Trial)|
|Actual Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Comparison of Two Dosage Adjustment Strategies of Vancomycin in Children|
|Actual Study Start Date :||February 23, 2016|
|Actual Primary Completion Date :||February 15, 2017|
|Estimated Study Completion Date :||April 2017|
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.
- Proportion of subjects with vancomycin AUC/MIC ≥ 400 and serum trough concentration ≤ 20 mg/L [ Time Frame: 24th hour of treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02694458
|Hôpital Necker-Enfants Malades|
|Paris, France, 75015|
|Principal Investigator:||Jean-Marc TRELUYER, MD, PhD||Hôpital Necker-Enfants Malades|