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.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

• social sciences sociology demography mortality
• medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Neonatal seizures
• PK/PD
• bumetanide
• drug development
• off-patent
• randomised controlled trial

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-HEALTH - Specific Programme "Cooperation": Health

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• HEALTH-2009-4.2-1 - Adapting off-patent medicines to the specific needs of paediatric populations

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

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

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

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

Coordinator

Participants (14)