Emergencies
Conditions
Brief 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.
Detailed 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
Interventions
None listed
Sponsors
Rennes University Hospital
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 44 Weeks
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement rate of therapeutic efficacy target of metronidazole | 1 week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | 1 week | Recording of adverse events (clinical and / or biological) during the treatment period and up to the end of the hospitalisation |
| Minimum Inhibitory Concentration | 1 week | 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 |
| Concentration of metronidazole un peritoneal fluid | 1 week | 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 |
| average clearance | 1 week | 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 |
| Impact of age | 1 week | 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 |
| Impact of weight | 1 week | 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 |
| Impact of therapeutic associations | 1 week | 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 |
| volume of distribution | 1 week | 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 |
| interindividual variability | 1 week | 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 |
| residual variability | 1 week | 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 |
Countries
France
Outcome results
None listed