Levetiracetam Treatment of Neonatal Seizures

Neonatal Seizures Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02602015
• Other study ID #: PHDehong_NNICU3
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: November 9, 2015
• Last updated: November 9, 2015
• Start date: November 2015
• Est. completion date: December 2018

Study information

• Verified date: November 2015
• Source: The People's Hospital of Dehong Autonomous Prefecture
• Contact: Zhaoqing Yin, bachelor
• Email: zhaoqingyin99[@]sina.com
• Is FDA regulated: No
• Health authority: China: Health and Family planning commision Dehong Autonomous Prefecture of Dai and Jingpo Ethnic Groups,Yunnnan Province
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 28 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neonatal Seizures
• Seizures

Intervention

Drug:
• Oral levetiracetam
Oral load of levetiracetam (50 mg/kg) following identification of EEG confirmed neonatal seizure.
• Intravenous phenobarbital
Intravenous load of phenobarbital (20 mg/kg)following EEG confirmation of seizure activity load.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
The People's Hospital of Dehong Autonomous Prefecture	Children's Hospital of Fudan University, Guangzhou Women and Children's Medical Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Maternal and Child Health Hospital of Hubei Province, Second Affiliated Hospital of Wenzhou Medical University, Xiamen Children's Hospital, Fujian of China

References & Publications (10)

Auvin S, Chhun S, Berquin P, Ponchel E, Delanoë 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. — View 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. — View Citation

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. — View 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. — View Citation

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. — View 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. — View 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. — View Citation

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate and extent of absorption by assessment of tmax	Comparison of tmax (time to reach maximum plasma concentration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).	On 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 postdose)	Yes
Other	Rate and extent of absorption by assessment of Cmax	Comparison of Cmax (maximum observed plasma concentration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).	On 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 postdose)	Yes
Other	Rate and extent of absorption by assessment of AUC(0-4)	Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).	On 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)	Yes
Other	Rate and extent of absorption by assessment of Cmax,ss of levetiracetam	Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. 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).	On 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)	Yes
Other	Rate and extent of absorption by assessment of AUC(0-24) of levetiracetam	Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. 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).	On 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)	Yes
Other	Rate and extent of absorption by assessment of tmax,ss of levetiracetam	Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. 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).	On 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)	Yes
Other	Rate and extent of absorption by assessment of Cavg,ss of levetiracetam	Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. 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).	On 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)	Yes
Other	Rate and extent of absorption by assessment of AUC(0-last) of levetiracetam	Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) of levetiracetam (i.e. in subjects with intensive pharmacokinetic assessments)	On 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)	Yes
Other	Rate and extent of absorption following multiple dose administration by assessment of Cmin of levetiracetam	Comparison of Cmin (predose concentration) of levetiracetam in each treatment period.	On Day 1 and on Day 14 at pre-dose in each period	Yes
Primary	EEG	Efficacy of levetiracetam by assessment of the change from baseline in EEG on Day 15.	On Day 1	No
Primary	EEG	Efficacy of levetiracetam by assessment of the change from baseline in EEG on Day 15.	On Day 15	No
Secondary	Brain Parenchyma Alterations(MRI)	Efficacy of levetiracetam by assessment of the change of brain from baseline in MRI on Day 28.	On Day 28 in each period	No
Secondary	Neurodevelopment(Bayley Scores)	Efficacy of levetiracetam by assessment of the change from baseline to Day 28 in neurodevelopment via Bayley Scores of Infant Development Mental Development Index (BSID).	On Day 28	No
Secondary	Seizure Control Days	Efficacy of levetiracetam by assessment of seizure control days.	From Day 1 to Day 28 post-dose in each period	No
Secondary	Number of Adverse Events(Abnormal Appearance)	This is a composition of general appearance, abdomen, skin, head and neck (including ears, eyes, nose,and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.	From Day 1 to Day 28 post-dose in each period	Yes
Secondary	Number of Adverse Events(Abnormal Blood Pressure)		From Day 1 to Day 28 post-dose in each period	Yes
Secondary	Number of Adverse Events(Pulse)		From Day 1 to Day 28 post-dose in each period	Yes
Secondary	Number of Adverse Events(Respiratory)		From Day 1 to Day 28 post-dose in each period	Yes
Secondary	Number of Abnormal Clinical Chemistry	Safety of levetiracetam by assessment of safety laboratory tests.	From Day 1 to Day 28 post-dose in each period	Yes
Secondary	Number of Abnormal Hematology	Safety of levetiracetam by assessment of safety laboratory tests.	From Day 1 to Day 28 post-dose in each period	Yes
Secondary	Number of Abnormal Clinical Urinalysis	Safety of levetiracetam by assessment of safety laboratory tests.	From Day 1 to Day 28 post-dose in each period	Yes