Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age With Probable and Confirmed Meningitis

Study Overview
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Brief Summary
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This phase I-II multicenter international trial is designed to study the pharmacokinetics of meropenem and to characterize the safety profile of meropenem in the treatment of infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis.

Detailed Description
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The primary objective will be to study the pharmacokinetics (plasma and cerebrospinal fluid) of meropenem in infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis and to characterize the safety profile of meropenem in the treatment of infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis. The secondary objectives are : To describe the efficacy of meropenem on day 3, at end of allocated treatment (EOAT), at test of cure (TOC) and at follow up (FU). To evaluate survival at FU To evaluate further episodes of meningitis (relapse or new infection) occurring between TOC and FU visits To define the organisms causing neonatal meningitis To describe the antibacterial susceptibility of meningitis-causing organisms and to describe the clinical and microbiological response according to this To evaluate mucosal colonization by resistant organisms before and after treatment with meropenem To evaluate bacterial eradication To evaluate functional genetic parameters that may affect response to therapy

Official Title
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Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age (Inclusive) With Probable and Confirmed Meningitis: A European Multicenter Phase I-II Trial

Conditions
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Meningitis

Intervention / Treatment
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* Drug: Meropenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent form signed by the parents/carers Chronological age below 90 days inclusive The presence of: clinical signs consistent with BM (hyperthermia or hypothermia or temperature instability PLUS 1 or more neurological findings among coma, seizures, neck stiffness, apnoea, bulging fontanelle), OR CSF pleocytosis (≥ 20 cells/mm3) OR a positive Gram stain of CSF. Exclusion Criteria: Presence of a CSF device Proven viral or fungal meningitis Severe congenital malformations if the infant is not to expect to survive for more than 3 months Other situations where the treating physician considers a different empiric antibiotic regimen necessary Known intolerance or contraindication to the study medication Participation in any other clinical study of an investigational medicinal product Renal failure and requirement of haemofiltration or peritoneal dialysis Meningitis with an organism known to be resistant to meropenem

Ages Eligible for Study
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Maximum Age: 90 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Meropenem<br>Infants will received Meropenem 40 mg/kg every 8 hours (every 12 hours in the youngest age group: < 32 weeks GA and < 2 weeks postnatal age). Treatment duration = 21 ± 7 days | Drug: Meropenem<br>* 40 mg/kg every 8 hours (every 12 hours in the youngest age group: < 32 weeks GA and < 2 weeks postnatal age). Treatment duration = 21 ± 7 days<br>* Other names: Meropenem trihydrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis. | Pharmacokinetic analyses (AUC) will be carried out on the infants who received at least one dose of meropenem after inclusion in NeoMero-2. The final model will be used for dosing simulations to give final dose recommendations. | 3-4 days | 
| Nature, frequency and numbers of all adverse events under meropenem. | Adverse events will also be summarised according to the need of a specific medical intervention or not. Analyses by time period will also be shown (from D0 to TOC visit and from TOC visit to follow-up). | Up to 48 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a favourable outcome defined at Test of Cure visit (TOC). | Patients with a favourable outcome defined at Test of Cure visit (TOC) 2 days after EOAT is met as an infant fulfilling the following criteria: Alive with clinical and bacteriological resolution of the abnormalities that defined BM at entry and no occurrence of any new clinical or laboratory abnormalities requiring a new course of antibiotic therapy and no modification of the initial meropenem therapy (for more than 24 hours). | An expected average of 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningitis, Neonates, Meropenem