Clinical Trial: Pilot Study of Bumetanide for Newborn Seizures

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Pilot Study of Bumetanide for Newborn Seizures: A Phase I Study of Pharmacokinetics and Safety of Bumetanide for Neonatal Seizures

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.

Detailed Summary:

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 do
Sponsor: Soul, Janet , M.D.

Current Primary Outcome: The primary outcome is determination of the pharmacokinetics and safety of bumetanide in newborns with refractory seizures. [ Time Frame: 5-6 years are anticipated for collection of the neonatal data ]

Original Primary Outcome: The primary outcome is determination of the pharmacokinetics of bumetanide in newborns with refractory seizures. [ Time Frame: Two years are anticipated for collection of the neonatal data ]

Current 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: 5-6 years are anticipated for collection of the neonatal data ]

Original Secondary Outcome:

• A secondary outcome is determination of the safety and tolerability of bumetanide as add-on therapy in newborns with refractory seizures. [ Time Frame: Two years is anticipated ]
• The secondary outcome will be to determine whether there is a dose-dependent effect of bumetanide compared with standard therapy alone for the control of seizures, quantified by EEG measures of seizure activity. [ Time Frame: Two and a half years is anticipated ]

Dates:
Date Received: January 27, 2009
Date Started: January 2010
Date Completion: December 2017
Last Updated: April 18, 2017
Last Verified: April 2017