Clinical trial NCT02550028: Levetiracetam Treatment of Neonatal Seizures
Official title: Levetiracetam Treatment of Neonatal Seizures: A Multi-Centre Randomized Blinded Controlled Study of the Efficacy of Oral Levetiracetam as First Line Treatment for Neonatal Seizures in China
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Neonatal Seizures
Keywords: Neonates
Seizure
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: Xiamen Children's Hospital, Fujian of China
name: Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
name: Guangzhou Women and Children's Medical Center
name: Second Affiliated Hospital of Wenzhou Medical University
name: Maternal and Child Health Hospital of Hubei Province
name: The Maternal & Children Health Hospital of Dehong, Yunnan of China
First posted: 2015-09-15
Enrollment: 60
Sex: ALL
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory. A multi-centre Chinese clinical trials with the aim to using oral Levetiracetam to develop new treatment strategies for the treatment of neonatal seizures. The purpose of this study is to determine the correct oral dosing, safety and efficacy for oral Levetiracetam as first line treatment in term new born babies with seizures.

Detailed description: This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects. Levetiracetam has great potential as a treatment for neonatal seizures but is not approved for use in children less than 1 years of age by oral. This study aims to obtain essential data regarding the efficacy and safety of oral Levetiracetam in neonatal population and simultaneously to use EEG monitoring systems that facilitate seizure detection and research.

Specific aims are:

1. To determine the efficacy of oral Levetiracetam in terminating neonatal seizures by EEG in the Neonatal Neurological Intensive Care Unit (NNICU).
2. To determine dose escalation data by studying the additional efficacy of a further dose in non responders.
3. To determine additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study.
4. To determine further safety data of oral Levetiracetam in neonates.

Eligibility criteria: Inclusion Criteria:

Neonatal seizure occurred and was proved by EEG according to abnormal discharge of brain. one or more of the following :

1. Male or female term baby with gestational \>37 weeks and postnatal age \< or= 28 days
2. Birthweight \>2500g
3. Written informed consent of parent or guardian

Exclusion Criteria:

1. Babies who have been close to death
2. Seizure occurred by metabolic factors (hypoglycemia, hypocalcemia, electrolyte disorder)
3. Babies who have received phenobarbitone or any other anticonvulsive medication before hospitalization
4. Abnormal renal function

Primary outcomes:
measure: EEG
timeFrame: At Day 28
Secondary outcomes:
measure: Brain Parenchyma Alterations(MRI)
timeFrame: At Day 28
measure: Neurodevelopment(Bayley Scores)
timeFrame: At Day 28
measure: Seizure Control Days
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Adverse Events（Abnormal Appearance）
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Adverse Events（Abnormal Blood Pressure）
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Adverse Events(Pulse)
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Adverse Events(Respiratory)
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Abnormal Clinical Chemistry
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Abnormal Hematology
timeFrame: From Day 1 to Day 28 post-dose in each period
measure: Number of Abnormal Clinical Urinalysis
timeFrame: From Day 1 to Day 28 post-dose in each period
Other outcomes:
measure: Rate and extent of absorption by assessment of tmax
timeFrame: At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
measure: Rate and extent of absorption by assessment of Cmax
timeFrame: At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
measure: Rate and extent of absorption by assessment of AUC(0-4)
timeFrame: At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
measure: Rate and extent of absorption by assessment of Cmax,ss of levetiracetam
timeFrame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
measure: Rate and extent of absorption by assessment of AUC(0-24) of levetiracetam
timeFrame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
measure: Rate and extent of absorption by assessment of tmax,ss of levetiracetam
timeFrame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
measure: Rate and extent of absorption by assessment of Cavg,ss of levetiracetam
timeFrame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
measure: Rate and extent of absorption by assessment of AUC(0-last) of levetiracetam
timeFrame: At Day 1 and Day 14 in each period (in subjects with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
measure: Rate and extent of absorption following multiple dose administration by assessment of Cmin of levetiracetam
timeFrame: At Day 1 and on Day 14 at pre-dose in each period
Locations:
city: Shanghai
country: China
facility: Children Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Wenhao Zhou, Doctor
role: STUDY_CHAIR
References:
citation: Garrity LC, Turner M, Standridge SM. Increased levetiracetam clearance associated with a breakthrough seizure in a pregnant patient receiving once/day extended-release levetiracetam. Pharmacotherapy. 2014 Jul;34(7):e128-32. doi: 10.1002/phar.1439. Epub 2014 May 7.
citation: Bansal S, Blalock D, Kebede T, Dean NP, Carpenter JL. Levetiracetam versus (fos)phenytoin for seizure prophylaxis in pediatric patients with intracranial hemorrhage. J Neurosurg Pediatr. 2014 Feb;13(2):209-15. doi: 10.3171/2013.10.PEDS13256. Epub 2013 Nov 29.
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citation: Kanemura H, Sano F, Sugita K, Aihara M. Effects of levetiracetam on seizure frequency and neuropsychological impairments in children with refractory epilepsy with secondary bilateral synchrony. Seizure. 2013 Jan;22(1):43-7. doi: 10.1016/j.seizure.2012.10.003. Epub 2012 Nov 3.
citation: Liu YH, Wang XL, Deng YC, Zhao G. Levetiracetam-associated aggravation of myoclonic seizure in children. Seizure. 2012 Dec;21(10):807-9. doi: 10.1016/j.seizure.2012.08.008. Epub 2012 Sep 16.
citation: Jehi LE, Irwin AI, Kayyali H, Vadera S, Bingaman W, Najm I. Levetiracetam may favorably affect seizure outcome after temporal lobectomy. Epilepsia. 2012 Jun;53(6):979-86. doi: 10.1111/j.1528-1167.2012.03453.x. Epub 2012 Mar 29.
citation: Steinbaugh LA, Lindsell CJ, Shutter LA, Szaflarski JP. Initial EEG predicts outcomes in a trial of levetiracetam vs. fosphenytoin for seizure prevention. Epilepsy Behav. 2012 Mar;23(3):280-4. doi: 10.1016/j.yebeh.2011.12.005. Epub 2012 Feb 16.
citation: Auvin S, Chhun S, Berquin P, Ponchel E, Delanoe C, Chiron C. Aggravation of absence seizure related to levetiracetam. Eur J Paediatr Neurol. 2011 Nov;15(6):508-11. doi: 10.1016/j.ejpn.2011.05.007. Epub 2011 Jun 15.