Neonatal SeizuresPhase 1/2NEMO1NCT01434225
NEMO1:NEonatal Seizure Using Medication Off-patent
A Phase 1/2 study testing Bumetanide in people with Neonatal Seizures, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 7 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 48 hours
- Conditions the study is for
- Neonatal Seizures
- What is being tested?
- Bumetanide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Aug 2011to Jun 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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.
Who cannot join
- 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 locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Netherlands2 sites
Erasmus Universitair Medisch Centrum Rotterdam
Rotterdam
University Medical Centre Utrecht
Utrecht, 3508 AB
Sweden2 sites
Karolinska Institutet and University Hospital
Stockholm
Uppsala University Hospital
Uppsala
United Kingdom2 sites
Leeds General Infirmary
Leeds
University College London Hospitals NHS Foundation Trust
London
About this study
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
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
- Being tested
- Bumetanide
- Keywords
- Neonatal seizures, Hypoxic Ischemic Encephalopathy, Electroencephalography, Bumetanide
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BumetanideDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Bumetanide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2011 (estimated)
- Study startAug 2011
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neonatal SeizuresStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- Ronit Pressler, Dr, Principal investigator, Great Ormond Street Hospital for Children NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434225
- Sponsor's protocol ID
- 08NR26
- Acronym
- NEMO1
- Status last verified
- Sep 2015
- First submitted
- 9 Sep 2011
- Last updated
- 14 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25765333
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01434225
- Acronym / sponsor ID
- NEMO1 / 08NR26
- Conditions
- Neonatal Seizures
- Keywords
- Neonatal seizures, Hypoxic Ischemic Encephalopathy, Electroencephalography, Bumetanide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- 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
- Study start
- Aug 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 14 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bumetanide | Experimental | Drug: BumetanideBumetanide - 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). |
Who may qualify
- Ages
- Up to 48 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (7 listed)
- Suspected or confirmed brain malformation, inborn error of metabolism,genetic syndrome, or major congenial malformation
- Congenital (in utero) infection (TORCH).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BumetanideBumetanide - 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 |
Primary outcome
Optimal dose finding
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2015.
- Derived from this study: PubMed 25765333Pressler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronit Pressler, Dr principal investigator
Great Ormond Street Hospital for Children NHS Foundation Trust
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bumetanide in people with Neonatal Seizures, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands, Sweden, United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal dose finding (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01434225, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2015.