Levetiracetam to Prevent Post-Traumatic Epilepsy

Epilepsy Clinical Trial

Official title:

Pilot: Levetiracetam to Prevent Post-Traumatic Epilepsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01463033
• Other study ID #: NS45656
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2011
• Last updated: December 11, 2015
• Start date: April 2005
• Est. completion date: February 2010

Study information

• Verified date: December 2015
• Source: Children's Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Head injury is the cause of approximately 5% of all epilepsy in the US. Past attempts at preventing epilepsy by treatment with older antiepileptic drugs have been unsuccessful. Levetiracetam is a novel AED with potent antiepileptogenic properties in animal models of epilepsy. It has a favorable side effect and pharmacokinetic profile. It is therefore a strong candidate for a clinical trial of epilepsy prevention following traumatic brain injury (TBI). However, there has been no experience in administering levetiracetam rapidly to individuals with acute TBI. The investigators propose to initiate the evaluation of levetiracetam in prevention of post-traumatic epilepsy by determining the safety, tolerability, pharmacokinetics and feasibility of acute and chronic administration of levetiracetam to individuals with head injury with a high risk for developing post-traumatic epilepsy. Further, the investigators will follow subjects for 2 years after injury in order to obtain pilot data about effect of levetiracetam on PTE. This pilot study is the first step in evaluation of levetiracetam in prevention of post-traumatic epilepsy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: February 2010
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Acute head injury associated with one of the following:

Intracranial hemorrhage, including epidural, subdural and intracerebral hemorrhage or with cerebral contusion(s) of any size; Penetrating (foreign body) head injury; Skull fracture and dural tear; Seizure within 8 hours of head injury

• Onset of head injury within 8-hours of proposed treatment initiation.

• Glasgow Coma Scale 6-15.

Exclusion Criteria:

• Clinical contraindications:

• Previous epilepsy or status epilepticus.

• Any systemic illness or unstable medical condition that might pose additional risk, including: renal insufficiency, other unstable metabolic or endocrine disturbances, and active systemic cancer.

• Psychosis within six months of enrollment as determined by history of hospitalization for psychosis or medications for psychosis.

• Moderate to severe mental retardation (IQ< 55 or>2 school grade levels below the expected for age [expected age = grade level +5]).

• Clinical/Laboratory Indicators:

• Serum creatinine > 1.5 on the day of treatment initiation for adults.

• Serum creatinine =1.5 for subjects =17 years old, =1.0 for subjects 13-17 years old and =0.7 for subjects 6-12 years old.

• Pregnancy

• Use of any CNS-active investigational drugs within 3 months of enrollment.

• Use of Antiepileptic Drugs (AEDs) within two months of enrollment, for any indication.

• Allergy/sensitivity to study drugs or their formulations:

• Active drug or alcohol dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements:

• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Epilepsy
• Epilepsy, Post-Traumatic
• Post-traumatic Epilepsy

Intervention

Drug:
• Levetiracetam
55 mg/kg/day given in 2 divided doses 12 hours apart

Locations

Country	Name	City	State
United States	Children's National Medical Center	Washington	District of Columbia
United States	MedStar Research Institute	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Pavel Klein	Medstar Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (3)

Klein P, Herr D, Pearl PL, Natale J, Levine Z, Nogay C, Sandoval F, Trzcinski S, Atabaki SM, Tsuchida T, van den Anker J, Soldin SJ, He J, McCarter R. Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttr — View Citation

Klein P, Herr D, Pearl PL, Natale J, Levine Z, Nogay C, Sandoval F, Trzcinsky S, Atabaki SM, Tsuchida T, van den Anker J, Soldin SJ, He J, McCarter R. Results of phase II pharmacokinetic study of levetiracetam for prevention of post-traumatic epilepsy. Ep — View Citation

Pearl PL, McCarter R, McGavin CL, Yu Y, Sandoval F, Trzcinski S, Atabaki SM, Tsuchida T, van den Anker J, He J, Klein P. Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy. Epilepsia. 2013 Se — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-Traumatic Epilepsy	occurrence of PTE (Post-Traumatic Epilepsy)	2 years	No
Secondary	Adverse Events	The 66 subjects with acute head injury with a high risk for developing post-traumatic epilepsy that received levetiracetam 55 mg/kg/day in a b.i.d. were monitored for adverse events through the 30 day treatment period.	30 day treatment period	No