NEMO1:NEonatal Seizure Using Medication Off-patent

Study Overview
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Brief Summary
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NEMO is a multicentre pan European clinical trial with the aim to develop new treatment strategies for the treatment of neonatal seizures using the loop diuretic bumetanide. There is evidence that bumetanide improves GABAergic function of the current standard drug, phenobarbitone. Bumetanide has been used as a diuretic in term and preterm babies for around thirty years. This trial should confirm that Bumetanide in addition to standard treatment will result in better seizures control.

Official Title
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NEMO1: An Open Label Exploratory Dose Finding and Pharmacokinetic Clinical Trial of Bumetanide for the Treatment of Neonatal Seizure Using Medication Off-patent

Conditions
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Neonatal Seizures

Intervention / Treatment
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* Drug: Bumetanide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:- Male or female term baby with gestational age of 37-43 weeks and postnatal age <48 hours One or more of the following: APGAR score < 5 at 5 mins. Umbilical cord or first arterial blood sample pH < 7.1 or base deficit >16 mmol/L. Postnatal resuscitation still required 10 minutes after birth Clinically evolving encephalopathy Received one dose of standard anticonvulsive therapy (phenobarbitone,20mg/kg) for clinical or electrographic seizures. EEG: equal to or more than 3 min cumulative seizures, or 2 or more seizures of >30 sec duration over 2 hr period within first 48 hr of life Written informed consent of parent or guardian. EEG monitoring has commenced within the first 48 hours of birth. Exclusion Criteria: Suspected or confirmed brain malformation, inborn error of metabolism,genetic syndrome, or major congenial malformation Congenital (in utero) infection (TORCH). Babies who have received diuretics such as furosemide or bumetanide in routine clinical management within the last 24 hours. Total serum bilirubin > 15 mg/dl (255 micromol/l) at inclusion. On any other anticonvulsive medication other than phenobarbitone or bolus of midazolam / pentobarbitone for intubation. Anuria/renal failure defined as serum creatinine > 200 micromol/l. Severe electrolyte depletion (Na <120 mmol/L, K <3.0 mmol/L)

Ages Eligible for Study
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Maximum Age: 48 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bumetanide<br>Bumetanide - Standard Phenobarbital plus either 0.05 mg/kg,0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg of bumetanide as determined by the the dose escalation design Maximum dose allowed is 0.3mg/kg given up to 4 times at 12 hourly intervals (total of 1.2mg/kg). | Drug: Bumetanide<br>* Bumetanide - Standard Phenobarbital plus either 0.05 mg/kg,0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg of bumetanide as determined by the the dose escalation design Maximum dose allowed is 0.3mg/kg given up to 4 times at 12 hourly intervals (total of 1.2mg/kg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal dose finding | The optimal dose is defined as achieving effective seizure reduction: Reduction of electrographic seizure (measuresd by EEG) burden by >80% during the 3rd and 4th hour after the first bumetanide administration compared to a 2 hour epoch prior to Bumetanide administration. No need for rescue AED within 48 hours | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal seizures, Hypoxic Ischemic Encephalopathy, Electroencephalography, Bumetanide