Clinical trial NCT01434225: NEMO1:NEonatal Seizure Using Medication Off-patent
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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neonatal Seizures
Keywords: Neonatal seizures
Hypoxic Ischemic Encephalopathy
Electroencephalography
Bumetanide
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Only For Children Pharmaceuticals
name: Cork University Hospital
name: UMC Utrecht
name: Helsinki University Central Hospital
name: Hôpital Necker-Enfants Malades
name: The Leeds Teaching Hospitals NHS Trust
name: Karolinska University Hospital
name: University College London Hospitals
name: Uppsala University Hospital
name: Erasmus Medical Center
First posted: 2011-09-14
Enrollment: 14
Sex: ALL
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Optimal dose finding
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: Cork University Maternity Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Universitair Medisch Centrum Rotterdam
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Stockholm
country: Sweden
facility: Karolinska Institutet and University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Ronit Pressler, Dr
role: PRINCIPAL_INVESTIGATOR
References:
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.