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Population Pharmacokinetics of Metronidazole in Neonates (METROPOP)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04031183
Recruitment Status : Not yet recruiting
First Posted : July 24, 2019
Last Update Posted : March 6, 2020
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

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.


Condition or disease
Emergencies

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

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Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Population Pharmacokinetics of Metronidazole in Neonates: Evaluation and Optimization of the Dose
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022



Primary Outcome Measures :
  1. Achievement rate of therapeutic efficacy target of metronidazole [ Time Frame: 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 Outcome Measures :
  1. Number of Adverse Events [ Time Frame: 1 week ]
    Recording of adverse events (clinical and / or biological) during the treatment period and up to the end of the hospitalisation

  2. Minimum Inhibitory Concentration [ Time Frame: 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

  3. Concentration of metronidazole un peritoneal fluid [ Time Frame: 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

  4. average clearance [ Time Frame: 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


  5. Impact of age [ Time Frame: 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


  6. Impact of weight [ Time Frame: 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


  7. Impact of therapeutic associations [ Time Frame: 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


  8. volume of distribution [ Time Frame: 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


  9. interindividual variability [ Time Frame: 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


  10. residual variability [ Time Frame: 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



Biospecimen Retention:   Samples Without DNA
Blood or peritoneal fluid drawn for routine biochemical tests


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 44 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Neonates (including both preterm and full-term neonates) receiving amoxicillin as part of their routine clinical care (for suspected or proven neonatal sepsis).
Criteria

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

Information from the National Library of Medicine

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): NCT04031183


Contacts
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Contact: Marie LE NAOU 0033(0)299289194 marie.lenaou@chu-rennes.fr
Contact: Stephanie Leroux, Phd 0033 (0)299284312 Stephanie.LEROUX@chu-rennes.fr

Locations
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France
CHU d'Angers
Angers, France
Contact: Bernard LEBOUCHER         
CHU de Brest
Brest, France
Contact: Jean-Michel ROUE         
Centre Robert Debré
Paris, France
Contact: Valérie BIRAN         
CHU de Rennes
Rennes, France
Contact: Stéphanie LEROUX, Phd    0033 (0)299284312    Stephanie.LEROUX@chu-rennes.fr   
Contact: Marie LE NAOU    0033(0)0299289194    marie.lenaou@chu-rennes.fr   
CH St Brieuc
Saint-Brieuc, France
Contact: Jennifer CHAUVEL         
CHU de Tours
Tours, France
Contact: Géraldine FAVRAIS         
CH Vannes
Vannes, France
Contact: Anna SEVESTRE         
Sponsors and Collaborators
Rennes University Hospital
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Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT04031183    
Other Study ID Numbers: 35RC18_8856_METROPOP
First Posted: July 24, 2019    Key Record Dates
Last Update Posted: March 6, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Emergencies
Disease Attributes
Pathologic Processes