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Treatment of NEonatal seizures with Medication Off-patent: evaluation of efficacy and safety of bumetanide

Treatment of NEonatal seizures with Medication Off-patent: evaluation of efficacy and safety of bumetanide

Objective

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.

Coordinator

UNIVERSITY COLLEGE LONDON

Address

Gower Street
Wc1e 6bt London

United Kingdom

Activity type

Other

EU Contribution

€ 926 970

Administrative Contact

Greta Borg-Carbott (Ms.)

Participants (14)

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UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK

Ireland

EU Contribution

€ 1 212 648

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

EU Contribution

€ 565 685

HELSINGIN JA UUDENMAAN SAIRAANHOITOPIIRIN KUNTAYHTYMÄ

Finland

EU Contribution

€ 228 409

UNIVERSITY OF LEEDS

United Kingdom

EU Contribution

€ 183 072

UPPSALA UNIVERSITET

Sweden

EU Contribution

€ 191 220

GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG

Germany

EU Contribution

€ 367 800

Only For Children Pharmaceuticals

France

EU Contribution

€ 742 214,04

UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Netherlands

EU Contribution

€ 307 362

ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS

France

EU Contribution

€ 74 855

DUKE UNIVERSITY

United States

EU Contribution

€ 108 160

KAROLINSKA INSTITUTET

Sweden

EU Contribution

€ 164 040

CLININFO SA

France

EU Contribution

€ 76 575

GREAT ORMOND STREET HOSPITAL FOR CHILDREN NATIONAL HEALTH SERVICE TRUST

United Kingdom

EU Contribution

€ 140 103,60

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Netherlands

EU Contribution

€ 81 689

Project information

Grant agreement ID: 241479

Status

Closed project

  • Start date

    1 October 2009

  • End date

    31 March 2015

Funded under:

FP7-HEALTH

  • Overall budget:

    € 7 020 774,08

  • EU contribution

    € 5 370 802,64

Coordinated by:

UNIVERSITY COLLEGE LONDON

United Kingdom