Skip to main content

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.

Field of science

  • /medical and health sciences/clinical medicine/paediatrics

Call for proposal

FP7-HEALTH-2009-single-stage
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

University College London
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 926 970
Administrative Contact
Greta Borg-Carbott (Ms.)

Participants (14)

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Ireland
EU contribution
€ 1 212 648
Address
Western Road
T12 YN60 Cork
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Mary Cusack (Ms.)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 565 685
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Annick Bertault (Ms.)
HELSINGIN JA UUDENMAAN SAIRAANHOITOPIIRIN KUNTAYHTYMÄ
Finland
EU contribution
€ 228 409
Address
Stenbackinkatu 9
00029 Helsinki
Activity type
Research Organisations
Administrative Contact
Anne Karikumpu (Ms.)
UNIVERSITY OF LEEDS
United Kingdom
EU contribution
€ 183 072
Address
Woodhouse Lane
LS2 9JT Leeds
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Kathy Brownridge (Ms.)
UPPSALA UNIVERSITET
Sweden
EU contribution
€ 191 220
Address
Von Kraemers Alle 4
751 05 Uppsala
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Inga Andersson (Ms.)
GABO:MI GESELLSCHAFT FUR ABLAUFORGANISATION:MILLIARIUM MBH & CO KG
Germany
EU contribution
€ 367 800
Address
Oskar Von Miller Ring 29
80333 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Birgit Fuchs (Ms.)
Only For Children Pharmaceuticals

Participation ended

France
EU contribution
€ 742 214,04
Address
Rue Henri Barbusse 35 Bis
75005 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Vincent Grek (Mr.)
UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands
EU contribution
€ 307 362
Address
Heidelberglaan 100
3584 CX Utrecht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Margot Van Der Starre (Dr.)
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
EU contribution
€ 74 855
Address
3 Avenue Victoria
75000 Paris
Activity type
Research Organisations
Administrative Contact
Christophe Misse (Mr.)
DUKE UNIVERSITY
United States
EU contribution
€ 108 160
Address
Allen Building 207
27708 Durham Nc
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Oshrat Benmoshe-Doriocourt (Ms.)
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 164 040
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Rolf Trana (Mr.)
CLININFO SA
France
EU contribution
€ 76 575
Address
Rue De Gerland 99 Entree 7
69007 Lyon
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Corinne Chevarier (Ms.)
GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST
United Kingdom
EU contribution
€ 140 103,60
Address
Great Ormond Street
WC1N 3JH London
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Jo Southern (Dr.)
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Netherlands
EU contribution
€ 81 689
Address
Dr Molewaterplein 40
3015 GD Rotterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Sandra Horsch (Dr.)