Levetiracetam Treatment of Neonatal Seizures

NCT02550028 | Terminated Phase 1 DMC

• 1 other identifier: CHFudanU_NNICU3
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Neonatal Seizures

Keywords

Neonates; Seizure

Outcome Measures

Primary Outcomes (1)

• EEG

  Efficacy of levetiracetam by assessment of the change from baseline in EEG on Day 15.

  At Day 28

Secondary Outcomes (10)

• Brain Parenchyma Alterations(MRI)

  At Day 28

• Neurodevelopment(Bayley Scores)

  At Day 28

• Seizure Control Days

  From Day 1 to Day 28 post-dose in each period

• Number of Adverse Events（Abnormal Appearance）

  From Day 1 to Day 28 post-dose in each period

• Number of Adverse Events（Abnormal Blood Pressure）

  From Day 1 to Day 28 post-dose in each period

Other Outcomes (9)

• Rate and extent of absorption by assessment of tmax

  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)

• Rate and extent of absorption by assessment of Cmax

  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)

• Rate and extent of absorption by assessment of AUC(0-4)

  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)

Study Arms (2)

Oral levetiracetam

EXPERIMENTAL

Oral levetiracetam 50 mg/kg loading dose. 10 mg/kg 8 hourly maintenance

Drug: Oral levetiracetam

Intravenous phenobarbital

ACTIVE COMPARATOR

Intravenous phenobarbital 20 loading dose (add to 40 mg/kg if seizure discontrol). 5 mg/kg 24 hourly maintenance

Drug: Intravenous phenobarbital

Interventions

Oral levetiracetam DRUG

Oral load of levetiracetam (50 mg/kg) following identification of EEG confirmed neonatal seizure.

Also known as: Keppra

Oral levetiracetam

Intravenous phenobarbital DRUG

Intravenous load of phenobarbital (20 mg/kg)following EEG confirmation of seizure activity load.

Also known as: phenobarbitone

Intravenous phenobarbital

Eligibility Criteria

• Age: Up to 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonatal seizure occurred and was proved by EEG according to abnormal discharge of brain. one or more of the following :
• Male or female term baby with gestational \>37 weeks and postnatal age \< or= 28 days
• Birthweight \>2500g
• Written informed consent of parent or guardian

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Xiamen Children's Hospital, Fujian of China: collaborator
• Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region: collaborator
• Guangzhou Women and Children's Medical Center: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Maternal and Child Health Hospital of Hubei Province: collaborator
• The Maternal & Children Health Hospital of Dehong, Yunnan of China: collaborator

Study Sites (1)

Children Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Related Publications (10)

• 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.

  PMID: 24807683 BACKGROUND

• 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.

  PMID: 24286154 BACKGROUND

• Fang Y, Wu X, Xu L, Tang X, Wang J, Zhu G, Hong Z. Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types. J Clin Neurosci. 2014 Jan;21(1):55-62. doi: 10.1016/j.jocn.2013.01.032. Epub 2013 Nov 11.

  PMID: 24231559 BACKGROUND

• Khan O, Cipriani C, Wright C, Crisp E, Kirmani B. Role of intravenous levetiracetam for acute seizure management in preterm neonates. Pediatr Neurol. 2013 Nov;49(5):340-3. doi: 10.1016/j.pediatrneurol.2013.05.008. Epub 2013 Aug 3.

  PMID: 23921284 BACKGROUND

• Inaba K, Menaker J, Branco BC, Gooch J, Okoye OT, Herrold J, Scalea TM, Dubose J, Demetriades D. A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis. J Trauma Acute Care Surg. 2013 Mar;74(3):766-71; discussion 771-3. doi: 10.1097/TA.0b013e3182826e84.

  PMID: 23425733 BACKGROUND

• 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.

  PMID: 23127775 BACKGROUND

• 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.

  PMID: 22990039 BACKGROUND

• 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.

  PMID: 22462729 BACKGROUND

• 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.

  PMID: 22342434 BACKGROUND

• 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.

  PMID: 21680209 BACKGROUND

MeSH Terms

Conditions

Seizures

Interventions

Levetiracetam; Phenobarbital

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Barbiturates; Pyrimidinones; Pyrimidines

Study Officials

• Wenhao Zhou, Doctor

  Children's Hospital of Fudan University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: September 15, 2015
• Study Start: September 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

CN (1)