NEMO1:NEonatal Seizure Using Medication Off-patent

Phase 1

Completed

• Conditions: Neonatal Seizures
• Interventions: Drug: Bumetanide

• Registration Number: NCT01434225
• Lead Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-09-09
• Study First Submitted QC: 2011-09-13
• Study First Posted: 2011-09-14
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Status Verified: 2015-09
• Last Update Submitted: 2015-09-11
• Last Update Posted: 2015-09-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bumetanide	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).

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (7)

Cork University Maternity Hospital; 🇮🇪 Cork, Ireland

Erasmus Universitair Medisch Centrum Rotterdam; 🇳🇱 Rotterdam, Netherlands

University Medical Centre Utrecht; 🇳🇱 Utrecht, Netherlands

Karolinska Institutet and University Hospital; 🇸🇪 Stockholm, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Leeds General Infirmary; 🇬🇧 Leeds, United Kingdom

University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom