SeizuresPhase 1NCT00830531
Pilot Study of Bumetanide for Newborn Seizures
A Phase 1 study testing Bumetanide in people with Seizures, run by Soul, Janet , M.D. at 4 sites in United States.
Trial summary
The main goal of the study is to obtain pharmacokinetic and safety data of bumetanide in newborns with refractory seizures. The overall hypothesis is that bumetanide, added to conventional antiepileptic (antiseizure) medications, will be a safe and well tolerated medication, compared with conventional antiepileptic… Read more about this study
- Who is it for?
- Ages Up to 44 weeks
- Conditions the study is for
- Seizures
- What is being tested?
- Bumetanide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2010to Jan 2019
- Phase
- Phase 1
- 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 44 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- newborns with a post-conceptional age of 33-44 weeks
- condition with risk for seizure:
- asphyxia
- intracranial hemorrhage
- suspected or confirmed stroke
- CNS infection
Show all 11Show fewer
- genetic syndrome
- focal or diffuse brain malformation
- idiopathic or presumed genetic etiology of seizures
- metabolic disorder other than electrolyte disturbances or those caused by renal failure
- suspected clinical seizure
Who cannot join
- have transient metabolic abnormalities (e.g., transient hypocalcemia) as the sole cause of seizures
- are receiving ECMO (extracorporeal membrane oxygenation) therapy because of alteration of bumetanide pharmacokinetics by ECMO
- have contraindications to bumetanide (as determined by treating physician)
- have received diuretics such as furosemide or BTN
- newborns with a total serum bilirubin > 15 mg/dL at enrollment
- newborns given ≥ 40mg/kg of phenobarbital
- loading doses of AEDs other than phenobarbital (those who receive levetiracetam are still eligible since levetiracetam does not affect bumetanide pharmacokinetics)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Tufts Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Pilot Study of Bumetanide for Newborn Seizures: A Phase I Study of Pharmacokinetics and Safety of Bumetanide for Neonatal Seizures
The main goal of the study is to obtain pharmacokinetic and safety data of bumetanide in newborns with refractory seizures. The overall hypothesis is that bumetanide, added to conventional antiepileptic (antiseizure) medications, will be a safe and well tolerated medication, compared with conventional antiepileptic drugs alone.
Read the detailed description
Seizures occur more often during the newborn period (2-3.5 per 1000 live births) than at any later age. Neonatal seizures can lead to frequent and serious long-term consequences in survivors, such as later epilepsy and significant cognitive and motor disabilities. Unfortunately there are no completely effective drugs to treat neonatal seizures. Anti-epileptic drugs (AEDs) currently used to treat neonatal seizures are generally ineffective and have significant potential for side effects. Furthermore, many of these AEDs have never been tested in a randomized study. Numerous experts have thus emphasized in the last few years the urgent need for randomized trials of potential new treatments for neonatal seizures. The investigators are conducting a pilot study of the drug bumetanide as one such potential and novel treatment. Bumetanide is a commercially available drug that has been used safely in newborns as a diuretic for many years with minimal side effects. Recent basic science research in animals has shown bumetanide to be very effective in reducing seizures in neonatal animals by blocking a specific chloride importer which is highly expressed in neonates but not in children and adults (1). Moreover, these experimental studies have shown bumetanide to be particularly effective against seizures when used in combination with phenobarbital (PB), which is the standard first drug given to treat neonatal seizures (2).
The investigators will conduct a randomized, double-blind, controlled, dose escalation study of BTN as add-on therapy to treat refractory seizures caused by HIE, focal or multi-focal stroke, intracranial hemorrhage, CNS infection, genetic syndrome, focal or diffuse brain malformation, idiopathic or presumed genetic etiology of seizures, or metabolic disorder other than electrolyte disturbances or those caused by renal failure not controlled by an initial loading dose of PB. The trial will test the feasibility of early enrollment of newborns with HIE, rapid application of a full montage EEG, and continuous review of EEG data to detect refractory seizures as soon as they occur following an initial loading dose of PB. When an EEG-proven seizure occurs at least 30 minutes following a loading dose of PB, the newborn will be randomized to receive either BTN or placebo in conjunction with a loading dose of PB. Clinical, laboratory and continuous EEG monitoring data obtained after BTN administration will be analyzed to determine the pharmacokinetics (3) and safety of BTN by comparing data from treatment and standard therapy groups. This study addresses important challenges in trial design and sets the stage for trials to improve treatment of neonatal seizures. Data from this pilot study will be used to guide design of a planned Phase III multicenter trial to test the efficacy of BTN to control refractory neonatal seizures.
- Conditions
- Seizures
- Being tested
- Bumetanide, Normal Saline as Placebo
- Keywords
- Hypoxic-ischemic encephalopathy, Neonatal stroke, Intracranial hemorrhage, Perinatal asphyxia, Neonatal Seizures
- Medical subject headings
- Seizures, Hypoxia-Ischemia, Brain, Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BumetanideDrug
Also called Bumex
Bumetanide either 0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg IV administered together with standard phenobarbital therapy
Normal Saline as PlaceboDrug
Also called 0.9% NaCl
Normal Saline as placebo for bumetanide either 0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg IV administered together with standard phenobarbital therapy
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Standard phenobarbital combined with either 0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg of bumetanide as determined by the status of the dose escalation design. Receives: Drug: Bumetanide |
| 2 | Placebo comparator | Standard phenobarbital therapy combined with normal saline as placebo for bumetanide Receives: Drug: Normal Saline as Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is determination of the pharmacokinetics and safety of bumetanide in newborns with refractory seizures.
The investigators will determine the dose exposure, half-life, volume of distribution and clearance of bumetanide in newborns with refractory seizures. The investigators will determine if there is a significant effect of hepatic dysfunction or hypothermia on bumetanide pharmacokinetics. For evaluation of safety, the rate of adverse events will be compared between treatment and control groups.
Measured: 6-7 years are anticipated for the collection of the neonatal data
Secondary outcomes (1)
A secondary outcome is determination of the feasibility of the study design to test antiepileptic drugs to treat neonatal seizures caused by acute hypoxic-ischemic encephalopathy in a clinical trial.
The investigators will determine the feasibility of enrolling and randomizing newborns early in the course of their refractory seizures.
Measured: 6-7 years are anticipated for collection of the neonatal data
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2009 (estimated)
- Study startJan 2010
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Soul, Janet , M.D.
- Collaborators
- Citizens United for Research in Epilepsy, Harvard Catalyst- Harvard Clinical and Translational Science Center, Boston Children's Hospital, Charles H. Hood Foundation, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Janet Soul, MD,CM, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00830531
- Sponsor's protocol ID
- CURE 07120492
- Other IDs
- 1R01NS066929-01A1
- Status last verified
- Dec 2020
- First submitted
- 27 Jan 2009
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dzhala VI, Talos DM, Sdrulla DA, Brumback AC, Mathews GC, Benke TA, Delpire E, Jensen FE, Staley KJ. NKCC1 transporter facilitates seizures in the developing brain. Nat Med. 2005 Nov;11(11):1205-13. doi: 10.1038/nm1301. Epub 2005 Oct 9.
PubMed 16227993Dzhala VI, Brumback AC, Staley KJ. Bumetanide enhances phenobarbital efficacy in a neonatal seizure model. Ann Neurol. 2008 Feb;63(2):222-35. doi: 10.1002/ana.21229.
PubMed 17918265Li Y, Cleary R, Kellogg M, Soul JS, Berry GT, Jensen FE. Sensitive isotope dilution liquid chromatography/tandem mass spectrometry method for quantitative analysis of bumetanide in serum and brain tissue. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Apr 15;879(13-14):998-1002. doi: 10.1016/j.jchromb.2011.02.018. Epub 2011 Feb 19.
PubMed 21414852
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Bumetanide for Newborn Seizures: A Phase I Study of Pharmacokinetics and Safety of Bumetanide for Neonatal Seizures
- ClinicalTrials.gov ID
- NCT00830531
- Acronym / sponsor ID
- CURE 07120492
- Conditions
- Seizures
- Keywords
- Hypoxic-ischemic encephalopathy, Neonatal stroke, Intracranial hemorrhage, Perinatal asphyxia, Neonatal Seizures
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Soul, Janet , M.D.
- Collaborators
- Citizens United for Research in Epilepsy, Harvard Catalyst- Harvard Clinical and Translational Science Center, Boston Children's Hospital, Charles H. Hood Foundation, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2010
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 28 Jan 2009 (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.
The main goal of the study is to obtain pharmacokinetic and safety data of bumetanide in newborns with refractory seizures. The overall hypothesis is that bumetanide, added to conventional antiepileptic (antiseizure) medications, will be a safe and well tolerated medication, compared with conventional antiepileptic drugs alone.
Detailed description
Seizures occur more often during the newborn period (2-3.5 per 1000 live births) than at any later age. Neonatal seizures can lead to frequent and serious long-term consequences in survivors, such as later epilepsy and significant cognitive and motor disabilities. Unfortunately there are no completely effective drugs to treat neonatal seizures. Anti-epileptic drugs (AEDs) currently used to treat neonatal seizures are generally ineffective and have significant potential for side effects. Furthermore, many of these AEDs have never been tested in a randomized study. Numerous experts have thus emphasized in the last few years the urgent need for randomized trials of potential new treatments for neonatal seizures. The investigators are conducting a pilot study of the drug bumetanide as one such potential and novel treatment. Bumetanide is a commercially available drug that has been used safely in newborns as a diuretic for many years with minimal side effects. Recent basic science research in animals has shown bumetanide to be very effective in reducing seizures in neonatal animals by blocking a specific chloride importer which is highly expressed in neonates but not in children and adults (1). Moreover, these experimental studies have shown bumetanide to be particularly effective against seizures when used in combination with phenobarbital (PB), which is the standard first drug given to treat neonatal seizures (2).
The investigators will conduct a randomized, double-blind, controlled, dose escalation study of BTN as add-on therapy to treat refractory seizures caused by HIE, focal or multi-focal stroke, intracranial hemorrhage, CNS infection, genetic syndrome, focal or diffuse brain malformation, idiopathic or presumed genetic etiology of seizures, or metabolic disorder other than electrolyte disturbances or those caused by renal failure not controlled by an initial loading dose of PB. The trial will test the feasibility of early enrollment of newborns with HIE, rapid application of a full montage EEG, and continuous review of EEG data to detect refractory seizures as soon as they occur following an initial loading dose of PB. When an EEG-proven seizure occurs at least 30 minutes following a loading dose of PB, the newborn will be randomized to receive either BTN or placebo in conjunction with a loading dose of PB. Clinical, laboratory and continuous EEG monitoring data obtained after BTN administration will be analyzed to determine the pharmacokinetics (3) and safety of BTN by comparing data from treatment and standard therapy groups. This study addresses important challenges in trial design and sets the stage for trials to improve treatment of neonatal seizures. Data from this pilot study will be used to guide design of a planned Phase III multicenter trial to test the efficacy of BTN to control refractory neonatal seizures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: BumetanideStandard phenobarbital combined with either 0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg of bumetanide as determined by the status of the dose escalation design. |
| 2 | Placebo comparator | Drug: Normal Saline as PlaceboStandard phenobarbital therapy combined with normal saline as placebo for bumetanide |
Who may qualify
- Ages
- Up to 44 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- newborns with a post-conceptional age of 33-44 weeks
- condition with risk for seizure:
- suspected clinical seizure
Key exclusion criteria (7 listed)
- have transient metabolic abnormalities (e.g., transient hypocalcemia) as the sole cause of seizures
- are receiving ECMO (extracorporeal membrane oxygenation) therapy because of alteration of bumetanide pharmacokinetics by ECMO
- have contraindications to bumetanide (as determined by treating physician)
- have received diuretics such as furosemide or BTN
- newborns with a total serum bilirubin > 15 mg/dL at enrollment
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 |
|---|---|---|
| BumetanideAlso: BumexBumetanide either 0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg IV administered together with standard phenobarbital therapy | Drug | 1 |
| Normal Saline as PlaceboAlso: 0.9% NaClNormal Saline as placebo for bumetanide either 0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg IV administered together with standard phenobarbital therapy | Drug | 2 |
Primary outcome
The primary outcome is determination of the pharmacokinetics and safety of bumetanide in newborns with refractory seizures.
Time frame: 6-7 years are anticipated for the collection of the neonatal data
The investigators will determine the dose exposure, half-life, volume of distribution and clearance of bumetanide in newborns with refractory seizures. The investigators will determine if there is a significant effect of hepatic dysfunction or hypothermia on bumetanide pharmacokinetics. For evaluation of safety, the rate of adverse events will be compared between treatment and control groups.
1 secondary outcome
A secondary outcome is determination of the feasibility of the study design to test antiepileptic drugs to treat neonatal seizures caused by acute hypoxic-ischemic encephalopathy in a clinical trial.
Time frame: 6-7 years are anticipated for collection of the neonatal data
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 17 Dec 2020.
- Background: PubMed 16227993Dzhala VI, Talos DM, Sdrulla DA, Brumback AC, Mathews GC, Benke TA, Delpire E, Jensen FE, Staley KJ. NKCC1 transporter facilitates seizures in the developing brain. Nat Med. 2005 Nov;11(11):1205-13. doi: 10.1038/nm1301. Epub 2005 Oct 9.
- Background: PubMed 17918265Dzhala VI, Brumback AC, Staley KJ. Bumetanide enhances phenobarbital efficacy in a neonatal seizure model. Ann Neurol. 2008 Feb;63(2):222-35. doi: 10.1002/ana.21229.
- Background: PubMed 21414852Li Y, Cleary R, Kellogg M, Soul JS, Berry GT, Jensen FE. Sensitive isotope dilution liquid chromatography/tandem mass spectrometry method for quantitative analysis of bumetanide in serum and brain tissue. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Apr 15;879(13-14):998-1002. doi: 10.1016/j.jchromb.2011.02.018. Epub 2011 Feb 19.
- Publication reporting bumetanide trial results, Annals of Neurology 2020Link provided by the sponsor.
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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.
Janet Soul, MD,CM principal investigator
Boston Children's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bumetanide in people with Seizures, run by Soul, Janet , M.D. at 4 sites in United States.
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 11 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 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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?
The primary outcome is determination of the pharmacokinetics and safety of bumetanide in newborns with refractory seizures. (time frame: 6-7 years are anticipated for the collection of the neonatal data). 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 NCT00830531, which also lists 3 linked publications.
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 17 Dec 2020; AzTrials last refreshed its copy on 6 Nov 2026.