FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2014/06/004659 [Registered on: 09/06/2014] Trial Registered Retrospectively
Last Modified On: 06/06/2014
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Does Levetiracetam reduce death/ control fits better than phenobarbitone in neonates 
Scientific Title of Study   Levetiracetam vs Phenobarbitone for the control of neonatal seizures: A double blind randomised controlled Trial 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Shruthi K Bharadwaj 
Designation  Senior Resident, DM Neonatology Fellow 
Affiliation  JIPMER 
Address  Division of Neonatology Department of Paediatrics JIPMER Pondicherry

Pondicherry
PONDICHERRY
605006
India 
Phone  9655021135  
Fax    
Email  skb.bmc@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr B Vishnu Bhat 
Designation  Professor and Head 
Affiliation  JIPMER 
Address  Division of Neonatology Department of Pediatrics JIPMER Dhanvantrinagar

Pondicherry
PONDICHERRY
605006
India 
Phone  9842351282  
Fax    
Email  drvishnubhat@yahoo.com  
 
Details of Contact Person
Public Query
 
Name  shruthi k bharadwaj 
Designation  senior resident 
Affiliation  JIPMER 
Address  House no F2, first floor, New MSR Quarters, Hostel complex, JIPMER, Dhanvantrinagar, Pondicherry

Pondicherry
PONDICHERRY
605006
India 
Phone  9655021135  
Fax    
Email  skb.bmc@gmail.com  
 
Source of Monetary or Material Support  
JIPMER 
 
Primary Sponsor  
Name  JIPMER 
Address  JIPMER, Dhanvantrinagar, Pondicherry - 605006 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Shruthi K Bharadwaj  JIPMER  Division of Neonatology, Department of Pediatrics JIPMER Puducherry 605006 Pondicherry PONDICHERRY
Pondicherry
PONDICHERRY 
9655021135

skb.bmc@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics Committee (Human studies)  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Neonatal seizures,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  levetiracetam  babies will receive initial loading of i.v levetiracetam 20mg/kg over 20 minutes followed by loading doses of 20mg/kg upto maximum 60mg/kg if seizures are persistent. Maintenance dose is started with 20mg/kg/day in 2 divided doses and increased upto 30mg/kg/day if needed. Drugs are continued until seizure control. Babies are assessed at discharge, if neurological status is normal and no seizures, then stopped. If neurologically abnormal, then maintainence dose of drug is continued till 3 months and reassessed at 3 months of age. 
Comparator Agent  Phenobarbitone  Babies will receive 20mg/kg of phenobarbitone i.v over 20 minutes, followed by 10mg/kg upto maximum of 40mg/kg in case of persistent seizures. Maintainance dose of 5mg/kg/day is given as a single dose. Drugs are continued until seizure control. Babies are assessed at discharge, if neurological status is normal and no seizures, then stopped. If neurologically abnormal, then maintainence dose of drug is continued till 3 months and reassessed at 3 months of age. 
 
Inclusion Criteria  
Age From  1.00 Day(s)
Age To  30.00 Day(s)
Gender  Both 
Details  Babies admitted to NICU with clinical seizures and babies who develop clinical seizures during NICU stay with
 Gestational age ≥ 32 wks
 Birth weight ≥ 1500g
ï‚§ Chronological age < 30 days
 
 
ExclusionCriteria 
Details  Babies admitted to NICU with seizures and babies who develop seizures during NICU stay with
ï‚§ Seizures due to hypoglycemia and hypocalcemia
ï‚§ Serum creatinine >2mg/dl
ï‚§ Major congenital anomalies
ï‚§ Prior use of any other anticonvulsants
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
Mortality and times taken for the clinical control of seizures upto 30 days of age or at discharge whichever is earlier  Mortality and times taken for the clinical control of seizures upto 30 days of age or at discharge whichever is earlier 
 
Secondary Outcome  
Outcome  TimePoints 
All cause death/ neurodevelopmental delay at 18 months of age
 
All cause death/ neurodevelopmental delay at 18 months of age
 
Adverse events and side effects between the two groups during hospital stay  Adverse events and side effects between the two groups during hospital stay 
 
Target Sample Size   Total Sample Size="300"
Sample Size from India="300" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   15/02/2014 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   None so far 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Seizures occur in 1% to 5% of infants during the first month of life (the neonatal period), which is one of the highest-risk periods for seizures during the human life span(1,2) and may adversely impact neurodevelopmental outcome(3). Currently there are no class A evidence-based guidelines for the pharmacologic treatment of neonatal seizures (4) and hence the treatment is highly varied (4). The most commonly used anticonvulsant   in neonatal period is phenobarbitone which acts via GABAnergic mechanisms(4,5).  But phenobarbitone  results in complete termination of electroencephalogrphically confirmed seizures in only around 43% f patients when used as a first line medication (6). Other first line medications such as phenytoin and the benzodiazepines are also incompletely efficacious, prompting clinicians to use a number of  other anticonvulsants with minimal supporting evidence of safety, tolerability, and efficacy in neonates(7,8). Also the GABA receptor on which the phenobarbitone acts is shown to be deficient in the neonatal brain.  Also studies have shown that  phenobarbital causes neuronal apoptosis in animal models, and long term adverse neurodevelopmental effects related to pheno-barbital have been demonstrated(9). Levetiracetam is increasingly being used as an antiepileptic drug in the neonatal period,and is recognized as an antiepileptic drug with neuroprotective properties(10,11). Koppelstäetter et al. reported on the use of levetiracetam in term and preterm neonates with rarely observed adverse effects in their analysis of surveys from neonatologists and pediatric neurologists (12). A study by Kilicdag et al. demonstrated a significant decrease in the number of apoptotic neuronal cells in a levetiracetam treated group of rat pups who underwent a hypoxic-ischemic brain injury (11). Several retrospective trials and a few randomised trials are there demonstrating the usefulness of levetiracetam in neonatal seizures(7,13–19). Levetiracetam has a better neurodevelopmental outcome compared to phenobarbitone (9). Pharmacokinetics of levetiracetam in neonates has been well studies and the dosing, routes of elimination are well described(20–24). Levetiracetam can easily be administered to neonates because of the oral solution and intravenous formulations. Furthermore, it has little serum protein binding, is not hepatically metabolized, creates no drug-to-drug interactions and levetiracetam has few known serious adverse side effects, in contrast to other antiseizure medications, which may cause cardiopulmonary depression, arrhythmia, and coagulopathy. Levetiracetam  could be safe and efficacious in treating neonatal seizures and hence this study comparing the efficacy of levetiracetam with phenobarbitone in acute control of seizures as well as the long term outcome.

Hypothesis - Levetiracetam is more effective in seizure reduction in neonates compared to phenobarbitone


 
Close