Population Pharmacokinetics of Metronidazole in Neonates

Emergencies Clinical Trial

— METROPOP  

Official title:

Population Pharmacokinetics of Metronidazole in Neonates: Evaluation and Optimization of the Dose

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04031183
• Other study ID #: 35RC18_8856_METROPOP
• Status: Recruiting
• Start date: May 29, 2020
• Est. completion date: March 2022

Study information

• Verified date: March 2020
• Source: Rennes University Hospital
• Contact: Marie LE NAOU
• Phone: 0033(0)299289194
• Email: marie.lenaou[@]chu-rennes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of NEOPOPI is to conduct a population pharmacokinetic study of metronidazole in neonates, in order to evaluate and optimize neonatal dose regimen.

There will be no change to the medication treatment received by participants. An opportunistic pharmacokinetic sampling approach will be followed: samples will be scavenged from blood or cerebrospinal fluid drawn for routine biochemical tests. In this way, no additional invasive tests will be needed.

Description:

• Administration of the antibiotic according to the usual procedures for prescribing services: in particular, neither the indications nor the doses nor the methods of administration are fixed by the protocol

• Opportunistic sampling strategy: no biological samples are specifically collected for the purposes of the study (measurements of concentrations on "bottoms" or "left-over" samples); the performance of this non-invasive sampling strategy has been previously demonstrated in the neonatal population.

• Micro-analytical method (assay of concentrations on micro-volumes, of the order of 50μL)

• Population pharmacokinetic analysis

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 44 Weeks

Eligibility

Inclusion Criteria:

• In case of birth at gestational age = 37 weeks of amenorrhea (SA): inclusion of children of postnatal age <28 days

• In case of birth at a gestational age <37 SA: inclusion of post-menstrual age children (ie gestational age + post-natal age) <44 SA 2. Benefiting from metronidazole antibiotic therapy, as part of their routine independent clinical management of the study, whether the targeted infection is suspected or proven 3. Social Security Affiliates 4. No opposition of parents to participation in the study

Non-Inclusion Critéria Treatment with metronidazole initiated before arrival in the investigative center (> 1 dose).

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Emergencies

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Brest	Brest
France	Centre Robert Debré	Paris
France	CHU de Rennes	Rennes
France	CH St Brieuc	Saint-Brieuc
France	CHU de Tours	Tours
France	CH Vannes	Vannes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement rate of therapeutic efficacy target of metronidazole	Achievement rate of therapeutic efficacy target of Metronidazole (ie percentage of neonates in whom metronidazole plasma concentration remains above the MIC of target organisms for more than 70% of the dose range). In accordance with the recommendations of the European Medicines Agency, the optimal dosage regimen is defined as leading to a probability of antibiotic therapy success of greater than or equal to 90%. Thus, it is necessary to determine the dosage regimen allowing the target of therapeutic efficacy to be reached (ie maintenance of the plasma concentration of metronidazole greater than the MIC of the targeted microorganisms for more than 70% of the dose) in at least 90% of treated neonates.	1 week
Secondary	Number of Adverse Events	Recording of adverse events (clinical and / or biological) during the treatment period and up to the end of the hospitalisation	1 week
Secondary	Minimum Inhibitory Concentration	Collection of MICs of metronidazole for isolated germs. For metronidazole the antibacterial activity is time-dependent, the predictor of efficacy is the "Time> MIC": this is the percentage of the administration interval during which the concentration of the antibiotic remains higher than the MIC of target germs	1 week
Secondary	Concentration of metronidazole un peritoneal fluid	Calculation of metronidazole concentration in peritoneal fluid / metronidazole plasma concentration when data permits (i.e. when prelevment performed as part of usual care, during treatment with metronidazole	1 week
Secondary	average clearance	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: - the precision of estimates of average clearance	1 week
Secondary	Impact of age	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: the impact of âge associations as explaining part of the pharmacokinetic variability of the antibiotic	1 week
Secondary	Impact of weight	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: the impact of weight as explaining part of the pharmacokinetic variability of the antibiotic	1 week
Secondary	Impact of therapeutic associations	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: the impact of therapeutic associations as explaining part of the pharmacokinetic variability of the antibiotic	1 week
Secondary	volume of distribution	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: - the precision of estimates of volume of distribution	1 week
Secondary	interindividual variability	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: - the precision of estimates of interindividual variability	1 week
Secondary	residual variability	Using the population pharmacokinetic model developed and validated (diagnostic plots, NPDE (Comets et al., 2008), and bootstrap), calculation of: - the precision of estimates of residual variability	1 week