E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
proven or suspected bacterial meningitis in neonates and infants up to
90 days of age |
|
E.1.1.1 | Medical condition in easily understood language |
meningitis in neonates and infants |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058780 |
E.1.2 | Term | Meningitis neonatal |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Microbiology substudy. 11.05.2011/version 1.0
Genetic determinants of susceptibility to sepsis and to differential responses to Meropenem. 11.05.2011/version 1.0 |
|
E.3 | Principal inclusion criteria |
Informed consent form signed by the parents/carers Chronological age below 90 days inclusive The presence of: clinical signs consistent with bacterial meningitis (clinical signs of meningitis are: fever or hypothermia or temperature instability PLUS 1 or more neurological findings e.g. coma, seizures, neck stiffness, apnoea, bulging fontanelle) OR CSF pleocytosis (≥ 20 cells / mm3 OR a positive Gram stain of CSF. |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The PK of meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed BM
Adverse events experienced by infants receiving meropenem. Clinical and biological adverse events will be recorded until FU visit. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
A favourable outcome defined at Test of Cure visit (TOC), 2 days after EOAT as an infant fulfilling the following criteria:
- Alive;
- Clinical and bacteriological* resolution (see appendix B) 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;
- No modification of the initial meropenem therapy (for more than 24 hours).
* In the case of microbiologically confirmed BM, microbiological eradication and no new pathogen identified |
|
E.5.2 | Secondary end point(s) |
Clinical, biological and microbiological response at day 3, at EOAT, at TOC and at FU; Survival at FU visit; Auditory function as assessed by brain-stem auditory evoked potentials between COT and FU visits; Neurological evaluation as assessed by cerebral ultrasound (and if persistently abnormal, by MRI or CT) at any time up until the FU visit; The organisms causing neonatal meningitis; |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The antibiotic susceptibility of bacteria causing BM; Mucosal colonisation with antibiotic resistant bacteria or fungi at enrolment, EOAT and FU / discharge (whichever is earlier) Genetic parameters that can affect response to therapy |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
IDMC performs an interim review of the trial's progress including
updated figures on recruitment, data quality, and main safety and
efficacy outcomes. Based on its review,
the IDMC will provide within 15 days after each of its meetings a brief formal written report with recommendations to the sponsor regarding study modification, continuation or termination. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |