Primairy objectivesTo study the pharmacokinetics (plasma and cerebrospinal fluid) of meropenem in infants
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Central nervous system infections and inflammations
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics: The final model will be used for dosing simulations to give
final dose recommendation.
Safety of meropenem: The nature, frequency and numbers of all adverse events
will be described.
Safety and pharmacokinetic analyses will be carried out on the infants who
received at least one dose of meropenem after inclusion in neomero 2.
Secondary outcome
- The proportion of infants receiving meropenem who have clinical and
bacteriological resolution of probable or confirmed BM will be assessed as a
secondary endpoint. This assessment will be made at 2 days after the end of
therapy (TOC visit). A favourable outcome is defined in an infant fulfilling
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.
* In the case of microbiologically confirmed BM, microbiological eradication
and no new pathogen identified
- Description of clinical, biological and microbiological response at day 3 at
EOAT, at TOC and at FU;
- Analysis of survival until FU;
- Description of a favourable outcome at TOC visit free of relapse at D45;
- Description of the organisms causing neonatal BM, their antimicrobial
susceptibility and response at TOC according to resistance;
- Analysis of the time to bacterial eradication;
- Description of mucosal colonisation with antibiotic resistant bacteria at
enrolment, EOAT and FU/discharge;
- Functional genetic parameters that can affect response to therapy;
- Auditory function parameters;
- Neurological evaluation parameters;
- Factors that could influence the efficacy outcome (introducing Vancomycin
after the start of treatment, comorbidities at inclusion, genetic parameters,
etc) will be studied in a logistic regression model.
Background summary
Bacterial meningitis in neonates is a serious disease that can be followed by
death in 10% to 30% of the cases. It can cause long-term disabilities in an
additional 20% to 50%.
The rise in resistance to conventional antibiotics is coupled with a reduction
in the pharmaceutical development of novel antibiotics against Gram-negative
bacteria, to replace those that are now less effective. This makes the choice
of empiric therapy difficult and clinicians are now challenged to employ a
combination of strategies for effective prevention and treatment of such
infections. Meropenem, a carbapenem, is an attractive candidate for empiric
therapy of meningitis and late-onset sepsis in the first 3 months of life
because it is active in vitro against a broad range of Gram-negative, including
ESBL producers, and Gram-positive aerobic and anaerobic bacteria including
Listeria monocytogenes.
Meropenem has been included in the revised EMEA *priority list for studies into
off patent paediatric medicinal products* (Doc. Ref.EMEA/226983/2008) with a
stated need for data on pharmacokinetics (PK), efficacy and safety of meropenem
in patients below 3 months of age. To overcome these shortcomings, the NeoMero2
project aims to evaluate safety and pharmacokinetic/pharmacodynamic
characteristics of meropenem in neonates and infants aged <3 months suffering
from BM. The results will facilitate the use of meropenem in neonates and
infants with meningitis more safely, assuring proper dosage. Data on dosing,
efficacy and safety could be included in the SPCs and PLs leading to a PUMA.
Consequently off label use in patients of less than 3 months of age could be
avoided.
Study objective
Primairy objectives
To study the pharmacokinetics (plasma and cerebrospinal fluid) of meropenem in
infants <= 90 days of postnatal age with probable or confirmed bacterial
meningitis (BM); To describe the safety profile of meropenem in the treatment
of infants <= 90 days of postnatal age with probable or confirmed bacterial
meningitis.
Secondary objectives
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 responses 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
A European multicenter open-label single arm study to evaluate the
pharmacokinetics and safety of meropenem in infants <= 90 days of age with
probable or confirmed bacterial meningitis.
Intervention
Infants will be treated with meropenem
Study burden and risks
The vast majority of the investigations that we are going to record will be
done in any case in order to help the child, even if the child does not take
part in this study. The extra blood samples will be taken as often as possible
when routine samples are taken to avoid pain and discomfort.
Meropenem could cause side effects. The most common side effects reported are
diarrhoea, rashes, nausea and vomiting.
There have been two studies that report that meropenem was well tolerated in
babies younger than three months of age.
Via Giustiniani 3
Padova 35128
IT
Via Giustiniani 3
Padova 35128
IT
Listed location countries
Age
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.
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-001521-25-NL |
| CCMO | NL37952.091.11 |