Pilot Study of Bumetanide for Newborn Seizures

NCT00830531 | Completed Phase 1 DMC

• 2 other identifiers: CURE 071204921R01NS066929-01A1
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Seizures

Keywords

Hypoxic-ischemic encephalopathy; Neonatal stroke; Intracranial hemorrhage; Perinatal asphyxia; Neonatal Seizures

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  6-7 years are anticipated for collection of the neonatal data

Study Arms (2)

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.

Drug: Bumetanide

2

PLACEBO COMPARATOR

Standard phenobarbital therapy combined with normal saline as placebo for bumetanide

Drug: Normal Saline as Placebo

Interventions

Bumetanide DRUG

Bumetanide either 0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg IV administered together with standard phenobarbital therapy

Also known as: Bumex

1

Normal Saline as Placebo DRUG

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

Also known as: 0.9% NaCl

2

Eligibility Criteria

• Age: Up to 44 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Soul, Janet , M.D.: lead
• Citizens United for Research in Epilepsy: collaborator
• Harvard Catalyst- Harvard Clinical and Translational Science Center: collaborator
• Translational Research Program, Boston Children's Hospital: collaborator
• Charles H. Hood Foundation: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Mooney Family Initiative for Translational Studies in Rare Diseases, Boston Children's Hospital: collaborator

Study Sites (4)

Tufts Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• 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.

  PMID: 16227993 BACKGROUND

• Dzhala 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.

  PMID: 17918265 BACKGROUND

• Li 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.

  PMID: 21414852 BACKGROUND

Related Links

• Publication reporting bumetanide trial results, Annals of Neurology 2020

MeSH Terms

Conditions

Seizures; Hypoxia-Ischemia, Brain; Intracranial Hemorrhages

Interventions

Bumetanide; Saline Solution

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Hemorrhage; Pathologic Processes

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Janet Soul, MD,CM

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 28, 2009
• Study Start: January 1, 2010
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: December 17, 2020

Record last verified: 2020-12

Locations

US (4)