NEMO1:NEonatal Seizure Using Medication Off-patent

NHS Foundation Trust

Status and phase: Completed; Phase 2; Phase 1

Conditions: Neonatal Seizures

Treatments: Drug: Bumetanide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01434225

08NR26

Details and patient eligibility

About

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.

Enrollment: 14 patients

Sex: All

Ages: Under 48 hours old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Bumetanide

Experimental group

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).

Treatment:

Drug: Bumetanide