Meningitis
Conditions
Keywords
Meningitis, Neonates, Meropenem
Brief summary
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
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
Interventions
DRUGMeropenem
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
Sponsors
Chiesi Farmaceutici S.p.A.
PENTA Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 90 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis. | 3-4 days | 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. |
| Nature, frequency and numbers of all adverse events under meropenem. | Up to 48 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with a favourable outcome defined at Test of Cure visit (TOC). | An expected average of 21 days | 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). |
Countries
United Kingdom
Outcome results
None listed