| 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 |
|
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Source of Monetary or Material Support
|
|
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Primary Sponsor
|
| Name |
JIPMER |
| Address |
JIPMER, Dhanvantrinagar, Pondicherry - 605006 |
| Type of Sponsor |
Research institution and hospital |
|
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Details of Secondary Sponsor
|
|
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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 |
|
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Regulatory Clearance Status from DCGI
|
|
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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. |
|
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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
|
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant and Outcome Assessor Blinded |
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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)?
|
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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
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