Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age With Probable and Confirmed Meningitis (NeoMero-2)

This study is currently recruiting participants.
Verified March 2013 by PENTA Foundation
Sponsor:
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
PENTA Foundation
ClinicalTrials.gov Identifier:
NCT01554124
First received: February 27, 2012
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Meningitis
Drug: Meropenem
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by PENTA Foundation:

Primary Outcome Measures:
  • Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis. [ Time Frame: 3-4 days ] [ Designated as safety issue: Yes ]

    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. [ Time Frame: Up to 48 days ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Percentage of patients with a favourable outcome defined at Test of Cure visit (TOC). [ Time Frame: An expected average of 21 days ] [ Designated as safety issue: Yes ]
    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).


Estimated Enrollment: 60
Study Start Date: February 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Meropenem

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

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

Other Name: Meropenem trihydrate

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

Ages Eligible for Study:   up to 90 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01554124

Locations
United Kingdom
HEATH, Paul Recruiting
London, Cranmer Terrace, United Kingdom, SW17 ORE
Contact: Tatiana Munera    + 44 02087255382    tmunerah@sgul.ac.uk   
Principal Investigator: Paul Heath         
Sponsors and Collaborators
PENTA Foundation
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Paul HEATH Paediatric Infectious Diseases St Georges, University of London
Study Chair: Jean-Pierre ABOULKER Institut National de la Santé Et de la Recherche Médicale, France
  More Information

Additional Information:
No publications provided

Responsible Party: PENTA Foundation
ClinicalTrials.gov Identifier: NCT01554124     History of Changes
Other Study ID Numbers: 2011-001521-25
Study First Received: February 27, 2012
Last Updated: March 12, 2013
Health Authority: Greece: Ethics Committee
Greece: National Organization of Medicines
Lithuania: Bioethics Committee
Lithuania: State Medicine Control Agency - Ministry of Health
Estonia: Research Ethics Committee
Estonia: The State Agency of Medicine
Italy: Ethics Committee
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Medicines Evaluation Board (MEB)
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by PENTA Foundation:
Meningitis
Neonates
Meropenem

Additional relevant MeSH terms:
Meningitis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014