NEMO1:NEonatal Seizure Using Medication Off-patent

This study has been completed.
Sponsor:
Collaborators:
Only For Children Pharmaceuticals
Cork University Hospital
UMC Utrecht
Helsinki University Central Hospital
Hôpital Necker-Enfants Malades
The Leeds Teaching Hospitals NHS Trust
Karolinska University Hospital
University College London Hospitals
Uppsala University Hospital
Erasmus Medical Center
Information provided by (Responsible Party):
Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01434225
First received: September 9, 2011
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Neonatal Seizures
Drug: Bumetanide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Great Ormond Street Hospital for Children NHS Foundation Trust:

Primary Outcome Measures:
  • Optimal dose finding [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    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


Estimated Enrollment: 49
Study Start Date: August 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   up to 48 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434225

Locations
Ireland
Cork University Maternity Hospital
Cork, Ireland
Netherlands
Erasmus Universitair Medisch Centrum Rotterdam
Rotterdam, Netherlands
University Medical Centre Utrecht
Utrecht, Netherlands, 3508 AB
Sweden
Karolinska Institutet and University Hospital
Stockholm, Sweden
Uppsala University Hospital
Uppsala, Sweden
United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
Only For Children Pharmaceuticals
Cork University Hospital
UMC Utrecht
Helsinki University Central Hospital
Hôpital Necker-Enfants Malades
The Leeds Teaching Hospitals NHS Trust
Karolinska University Hospital
University College London Hospitals
Uppsala University Hospital
Erasmus Medical Center
Investigators
Principal Investigator: Ronit Pressler, Dr Great Ormond Street Hospital for Children NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01434225     History of Changes
Other Study ID Numbers: 08NR26
Study First Received: September 9, 2011
Last Updated: June 19, 2013
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Research Ethics Committee
Ireland: Irish Medicines Board
Finland: Ethics Committee
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Medicines Evaluation Board (MEB)
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board

Keywords provided by Great Ormond Street Hospital for Children NHS Foundation Trust:
Neonatal seizures
Hypoxic Ischemic Encephalopathy
Electroencephalography
Bumetanide

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Bumetanide
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014