NEMO1:NEonatal Seizure Using Medication Off-patent

NCT01434225 | Completed Phase 1 DMC

• 1 other identifier: 08NR26
• Study Type: interventional
• Target: 14
• Locations: 4 countries
• Sites: 7

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.

Conditions

Neonatal Seizures

Keywords

Neonatal seizures; Hypoxic Ischemic Encephalopathy; Electroencephalography; Bumetanide

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Study Arms (1)

Bumetanide

EXPERIMENTAL

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

Interventions

Bumetanide DRUG

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).

Bumetanide

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead
• Only For Children Pharmaceuticals: collaborator
• Cork University Hospital: collaborator
• UMC Utrecht: collaborator
• Helsinki University Central Hospital: collaborator
• Hôpital Necker-Enfants Malades: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• Karolinska University Hospital: collaborator
• University College London Hospitals: collaborator
• Uppsala University Hospital: collaborator
• Erasmus Medical Center: collaborator

Study Sites (7)

Cork University Maternity Hospital

Cork, Ireland

Location

Erasmus Universitair Medisch Centrum Rotterdam

Rotterdam, Netherlands

Location

University Medical Centre Utrecht

Utrecht, 3508 AB, Netherlands

Location

Karolinska Institutet and University Hospital

Stockholm, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25765333 DERIVED

Related Links

• Study web site

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

Bumetanide

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• Ronit Pressler, Dr

  Great Ormond Street Hospital for Children NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: September 14, 2011
• Study Start: August 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: September 14, 2015

Record last verified: 2015-09

Locations

GB (2); IE (1); SE (2); NL (2)