NEMO1:NEonatal Seizure Using Medication Off-patent

Neonatal Seizures Clinical Trial

— NEMO1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01434225
• Other study ID #: 08NR26
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 9, 2011
• Last updated: September 11, 2015
• Start date: August 2011
• Est. completion date: June 2013

Study information

• Verified date: September 2015
• Source: Great Ormond Street Hospital for Children NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIreland: Research Ethics CommitteeIreland: Irish Medicines BoardFinland: Ethics CommitteeFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Committee for the Protection of PersonnesNetherlands: Medical Ethics Review Committee (METC)Netherlands: Medicines Evaluation Board (MEB)Sweden: Medical Products AgencySweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 48 Hours

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neonatal Seizures
• Seizures

Intervention

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).

Locations

Country	Name	City	State
Ireland	Cork University Maternity Hospital	Cork
Netherlands	Erasmus Universitair Medisch Centrum Rotterdam	Rotterdam
Netherlands	University Medical Centre Utrecht	Utrecht
Sweden	Karolinska Institutet and University Hospital	Stockholm
Sweden	Uppsala University Hospital	Uppsala
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	University College London Hospitals NHS Foundation Trust	London

Sponsors (11)

Lead Sponsor	Collaborator
Great Ormond Street Hospital for Children NHS Foundation Trust	Cork University Hospital, Erasmus Medical Center, Helsinki University Central Hospital, Hôpital Necker-Enfants Malades, Karolinska University Hospital, Only For Children Pharmaceuticals, The Leeds Teaching Hospitals NHS Trust, UMC Utrecht, University College London Hospitals, Uppsala University Hospital

Countries where clinical trial is conducted

Ireland,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes

External Links

•   Study web site