Neonatal Seizures
Conditions
Keywords
Neonatal seizures, Hypoxic Ischemic Encephalopathy, Electroencephalography, Bumetanide
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.
Interventions
DRUGBumetanide
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).
Sponsors
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
Great Ormond Street Hospital for Children NHS Foundation Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 48 Hours
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Ireland, Netherlands, Sweden, United Kingdom
Outcome results
None listed