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NEMO1:NEonatal Seizure Using Medication Off-patent (NEMO1)

Primary Purpose

Neonatal Seizures

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Bumetanide
Sponsored by
Great Ormond Street Hospital for Children NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neonatal Seizures focused on measuring Neonatal seizures, Hypoxic Ischemic Encephalopathy, Electroencephalography, Bumetanide

Eligibility Criteria

undefined - 48 Hours (Child)All SexesDoes not accept 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)

Sites / Locations

  • Cork University Maternity Hospital
  • Erasmus Universitair Medisch Centrum Rotterdam
  • University Medical Centre Utrecht
  • Karolinska Institutet and University Hospital
  • Uppsala University Hospital
  • Leeds General Infirmary
  • University College London Hospitals NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bumetanide

Arm Description

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
September 9, 2011
Last Updated
September 11, 2015
Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
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
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1. Study Identification

Unique Protocol Identification Number
NCT01434225
Brief Title
NEMO1:NEonatal Seizure Using Medication Off-patent
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
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

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neonatal Seizures
Keywords
Neonatal seizures, Hypoxic Ischemic Encephalopathy, Electroencephalography, Bumetanide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bumetanide
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Bumetanide
Intervention Description
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 Measure Information:
Title
Optimal dose finding
Description
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
Time Frame
6 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
48 Hours
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronit Pressler, Dr
Organizational Affiliation
Great Ormond Street Hospital for Children NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cork University Maternity Hospital
City
Cork
Country
Ireland
Facility Name
Erasmus Universitair Medisch Centrum Rotterdam
City
Rotterdam
Country
Netherlands
Facility Name
University Medical Centre Utrecht
City
Utrecht
ZIP/Postal Code
3508 AB
Country
Netherlands
Facility Name
Karolinska Institutet and University Hospital
City
Stockholm
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25765333
Citation
Pressler RM, Boylan GB, Marlow N, Blennow M, Chiron C, Cross JH, de Vries LS, Hallberg B, Hellstrom-Westas L, Jullien V, Livingstone V, Mangum B, Murphy B, Murray D, Pons G, Rennie J, Swarte R, Toet MC, Vanhatalo S, Zohar S; NEonatal seizure treatment with Medication Off-patent (NEMO) consortium. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2 trial. Lancet Neurol. 2015 May;14(5):469-77. doi: 10.1016/S1474-4422(14)70303-5. Epub 2015 Mar 10.
Results Reference
derived

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NEMO1:NEonatal Seizure Using Medication Off-patent

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