Obiettivo
Neonatal hypoxic ischaemic encephalopathy (HIE) occurs in 2-3/1000 live births and is a major cause of both acute mortality and long-term neurodisability. Seizures are the hallmark of HIE. The clinical and electrographic seizure burden in babies with HIE can be considerable and is often not reduced by current antiepileptic drugs. Phenobarbitone remains the first line drug for neonatal seizures despite the fact that it has limited efficacy. Better treatments for neonatal seizures, particularly in asphyxiated babies, are a high research priority with the ultimate aim to improve long-term outcome.
The aim of NEMO is to develop an effective treatment regimen for neonatal seizures using innovative strategies, targeted specifically to the needs and peculiarities of babies. An age dependent high expression of neuronal co-transporter resulting in excitatory rather than inhibitory function of GABA is believed to be responsible for the high incidence of seizures in the neonatal period. By blocking this co-transporter with bumetanide, a loop diuretic, the depolarizing action of GABA will be reversed resulting in reduced neuronal firing. Intensive EEG monitoring will enable us to accurately identify seizures and monitor treatment effect. A European-wide multicentre approach would, for the first time facilitate performing an RCT with enough statistical power in this age-group.
By consolidating efforts from basic science, pharmacology and clinical centres we propose:
1. to perform a European-wide, multicentre, randomised, placebo-controlled, double-blind trial to evaluate the efficacy and safety of bumetanide in neonates
2. to perform pharmacokinetic and pharmacodynamic studies of bumetanide
3. to further investigate the mechanisms of action in non-clinical experiments
4. to develop and adapt a bumetanide formulation suitable for neonates in order to apply for a Paediatric Use Marketing Authorization (PUMA).
5. if results of the initial trial do not support a PUMA application we plan to apply for a Paediatric Investigation Plan (PIP) for lidoocaine to assess its efficacy as an AED for the control of seizures which are not controlled by phenobarbitone.
Campo scientifico
Parole chiave
Argomento(i)
Invito a presentare proposte
FP7-HEALTH-2009-single-stage
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Meccanismo di finanziamento
CP-FP - Small or medium-scale focused research projectCoordinatore
WC1E 6BT LONDON
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Partecipanti (14)
T12 YN60 Cork
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75654 Paris
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00029 Helsinki
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LS2 9JT Leeds
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751 05 Uppsala
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80333 Muenchen
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Partecipazione conclusa
75005 Paris
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3584 CX Utrecht
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75012 Paris
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27708 Durham Nc
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17177 Stockholm
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69007 LYON
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WC1N 3JH London
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3015 GD Rotterdam
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