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

• ClinicalTrials.gov Identifier: NCT01554124
• Recruitment Status: Completed
• First Posted: March 14, 2012
• Last Update Posted: February 16, 2015
• Sponsor: PENTA Foundation
• Collaborator: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): PENTA Foundation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Meningitis	Drug: Meropenem	Phase 1; Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: February 2013
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis. [ Time Frame: 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.

2. Nature, frequency and numbers of all adverse events under meropenem. [ Time Frame: 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 Outcome Measures :

1. Percentage of patients with a favourable outcome defined at Test of Cure visit (TOC). [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: up to 90 Days (Child)
• Sexes Eligible for Study: All
• 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

Locations

United Kingdom

HEATH, Paul

London, Cranmer Terrace, United Kingdom, SW17 ORE

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:

Site dedicated to the NeoMero studies 

• Responsible Party: PENTA Foundation
• ClinicalTrials.gov Identifier: NCT01554124
• Other Study ID Numbers: 2011-001521-25
• First Posted: March 14, 2012
• Last Update Posted: February 16, 2015
• Last Verified: February 2015

Keywords provided by PENTA Foundation:

Meningitis; Neonates; Meropenem

Additional relevant MeSH terms:

Meningitis; Central Nervous System Diseases; Nervous System Diseases; Meropenem; Anti-Bacterial Agents; Anti-Infective Agents