Neonatal Seizures in Hypoxic Ischemic Encephalopathy MedDRA version: 15.0 Level: LLT Classification code 10061197 Term: Neonatal seizures System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Bumetanide 0.2mg/ml solution for IV administration
Product Code: bumetanide
Pharmaceutical Form: Solution for injection
Sponsors
Only for Children Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female term baby with gestational age of 37-43 weeks and postnatal age 16 mmol/L. Postnatal resuscitation still required 10 minutes after birth 3. Clinical evolving encephalopathy 4. Received one dose of standard anticonvulsive therapy (phenobarbitone, 20mg/kg) for clinical or electrographic seizures. 5. EEG: equal to or more than 3 min cumulative seizures, or 2 or more seizures of >30 sec duration over a 2 hr period within the first 48 hr of life and after administration of one standard (20mg/kg) dose of phenobarbitone 6. Written informed consent of parent or guardian. 7. EEG monitoring has commenced within the first 48 hours of birth Are the trial subjects under 18? yes Number of subjects for this age range: 49 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Suspected or confirmed brain malformation, inborn error of metabolism, genetic syndrome, or major congenial malformation 2. Congenital (in utero) infection (TORCH) if known. 3. Babies who have received diuretics such as furosemide or bumetanide in routine clinical management within the last 24 hours 4. On any other anticonvulsive medication other than phenobarbitone or or bolus of midazolam / pentobarbitone for intubation. 6. Severe electrolyte depletion (Na <120 mmol/L, K <3.0 mmol/L)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Stage 1 • To estimate the optimal dose of bumetanide for the treatment of neonatal seizures not responding to the first dose phenobarbitone. This optimum dose will be that which achieves the maximum seizure reduction with an acceptable safety profile when used in addition to standard therapy (second dose of phenobarbitone) in > 50% of patients Stage 2 • To determine the pharmacokinetics of bumetanide when given at the optimal dose as an add-on to phenobarbitone in babies with HIE and seizures not controlled by phenobarbitone ;Secondary Objective: • To assess the feasibility of neonatal seizure treatment with bumetanide in babies with HIE and seizures that are not responding to a first dose of phenobarbitone. • To assess whether bumetanide reduces the need for rescue medication. ;Primary end point(s): Stage 1 Efficacy: 1. Defined as reduction of electrographic seizure burden by =80% within hours 3 and 4 after the first bumetanide administration compared to the baseline; a 2 hour epoch immediately prior to the first Bumetanide administration 2. No need for rescue AED within 48 hours Safety: acceptable safety profile defined as 1. Absence of Suspected Unexpected Serious Adverse Reactions (SUSARs) 2. Serious Adverse Reactions (SAR) which are at least probably related in 1 hour) which requires inotropic support in <10%) Stage 2 1. PK measurements (bumetanide at the optimal dose);Timepoint(s) of evaluation of this end point: Stage 1 Efficacy: 1. Evaluated at hours 3 and 4 after the first bumetanide administration 2. Need for rescue AED evaluated at 48 hours after the first bumetanide administration Safety: acceptable safety profile continuously evaluated during the trial Stage 2 1. PK measurements (bumetanide at the optimal dose) analysis completed at the end of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Stage 1 1. PK measurements 2. Overall seizure control within the first 24 hr after bumetanide administration evaluated after the end of trial Stage 2 1. Safety of bumetanide in babies with HIE 2. Overall seizure control within the first 24 hr after bumetanide administration evaluated after the end of trial ;Timepoint(s) of evaluation of this end point: Stage 1 1. PK measurements analysis completed at the end of the trial. 2. Overall seizure control within the first 24 hr after bumetanide administration evaluated after the end of trial Stage 2 1. Safety of bumetanide in babies with HIE continuously evaluated during the trial 2. Overall seizure control within the first 24 hr after bumetanide administration evaluated after the end of trial | — |
Countries
Finland, Ireland, Netherlands, Sweden, United Kingdom
Contacts
Public ContactAlice Nolla
Only for Children Pharmacueticals
Outcome results
None listed