NEMO1:NEonatal Seizure Using Medication Off-patent

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust (Other)

Overall Status

Completed

CT.gov ID

NCT01434225

Collaborator

Only For Children Pharmaceuticals (Industry), Cork University Hospital (Other), UMC Utrecht (Other), Helsinki University Central Hospital (Other), Hôpital Necker-Enfants Malades (Other), The Leeds Teaching Hospitals NHS Trust (Other), Karolinska University Hospital (Other), University College London Hospitals (Other), Uppsala University Hospital (Other), Erasmus Medical Center (Other)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neonatal Seizures	Drug: Bumetanide	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bumetanide 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 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).

Arm

Intervention/Treatment

Experimental: Bumetanide

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

Outcome Measures

Primary Outcome Measures

Optimal dose finding [6 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 48 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cork University Maternity Hospital	Cork	Ireland
2	Erasmus Universitair Medisch Centrum Rotterdam	Rotterdam	Netherlands
3	University Medical Centre Utrecht	Utrecht	Netherlands	3508 AB
4	Karolinska Institutet and University Hospital	Stockholm	Sweden
5	Uppsala University Hospital	Uppsala	Sweden
6	Leeds General Infirmary	Leeds	United Kingdom
7	University College London Hospitals NHS Foundation Trust	London	United Kingdom