Clinical trial NCT01554124: Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age With Probable and Confirmed Meningitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Meningitis
Keywords: Meningitis
Neonates
Meropenem
Lead sponsor: PENTA Foundation
Sponsor class: NETWORK
Collaborators: name: Chiesi Farmaceutici S.p.A.
First posted: 2012-03-14
Enrollment: 51
Sex: ALL
Maximum age (years): 90
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis.
timeFrame: 3-4 days
measure: Nature, frequency and numbers of all adverse events under meropenem.
timeFrame: Up to 48 days
Secondary outcomes:
measure: Percentage of patients with a favourable outcome defined at Test of Cure visit (TOC).
timeFrame: An expected average of 21 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: HEATH, Paul
state: Cranmer Terrace
Study officials:
affiliation: Paediatric Infectious Diseases St Georges, University of London
name: Paul HEATH
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Jean-Pierre ABOULKER
role: STUDY_CHAIR
References: