Pilot Study of Bumetanide for Newborn Seizures
Information source: Soul, Janet , M.D.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Seizures
Intervention: Bumetanide (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Soul, Janet , M.D. Official(s) and/or principal investigator(s): Janet Soul, MD,CM, Principal Investigator, Affiliation: Children's Hospital Boston
Overall contact: Janet Soul, MD,CM, Phone: 617-355-8994, Email: janet.soul@childrens.harvard.edu
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 drugs alone.
Clinical Details
Official title: Pilot Study of Bumetanide for Newborn Seizures: A Phase I Study of Pharmacokinetics and Safety of Bumetanide for Neonatal Seizures
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: The primary outcome is determination of the pharmacokinetics and safety of bumetanide in newborns with refractory seizures.
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.
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 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.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- newborns with a post-conceptional age of 33-44 weeks
- condition with risk for seizure:
- asphyxia
- intracranial hemorrhage
- suspected or confirmed stroke
- CNS infection
- 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
Exclusion Criteria:
- 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)
Locations and Contacts
Janet Soul, MD,CM, Phone: 617-355-8994, Email: janet.soul@childrens.harvard.edu
Boston Children's Hospital, Boston, Massachusetts 02115, United States; Recruiting Janet Soul, MD, CM, Phone: 617-355-8994, Email: janet.soul@childrens.harvard.edu Janet Soul, MD, CM, Principal Investigator
Brigham and Women's Hospital, Boston, Massachusetts 02115, United States; Recruiting Helen Christou, MD, Phone: 617-525-8129, Email: HCHRISTOU@PARTNERS.ORG Helen Christou, MD, Principal Investigator
Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting Kevin J Staley, MD, Email: Staley.Kevin@mgh.harvard.edu Kevin J Staley, MD, Principal Investigator
Tufts Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts 02111, United States; Recruiting Jonathan Davis, MD, Email: jdavis@tuftsmedicalcenter.org Jonathan Davis, MD, Principal Investigator
Additional Information
Related 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. Epub 2005 Oct 9. Dzhala VI, Brumback AC, Staley KJ. Bumetanide enhances phenobarbital efficacy in a neonatal seizure model. Ann Neurol. 2008 Feb;63(2):222-35.
Starting date: January 2010
Last updated: April 17, 2015
|