Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age With Probable and Confirmed Meningitis - Full Text View

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:

MedlinePlus related topics: Meningitis

Drug Information available for: Meropenem

U.S. FDA Resources

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:

Site dedicated to the NeoMero studies This link exits the ClinicalTrials.gov site

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 May 19, 2013

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