IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures

Tracking Information
First Submitted Date ICMJE	July 31, 2007
First Posted Date ICMJE	August 2, 2007
Results First Submitted Date	January 8, 2011
Results First Posted Date	August 5, 2013
Last Update Posted Date	December 12, 2013
Study Start Date ICMJE	July 2007
Actual Primary Completion Date	December 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 1, 2013)	Number of Participants Who Experienced a Recurrent Seizure After Treatment. [ Time Frame: 24 hours ]; Recurrent seizure is defined as a seizure within 24 hours of treatment in the Emergency Department.
Original Primary Outcome Measures ICMJE; (submitted: July 31, 2007)	To determine if IV levetiracetam is safe and effective in preventing early recurrent seizures for 24 hours compared to phenytoin in patients who present to the ED within 4 hours of a tonic-clonic seizure (primary or secondarily generalized). [ Time Frame: 24 hours ]
Change History	Complete list of historical versions of study NCT00510783 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures
Official Title ICMJE	IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures
Brief Summary	This study is looking at three seizure medicines. Patients with seizures are usually treated with phenytoin (Dilantin) or Fosphenytoin. These medicines can be given intravenously (IV)or by mouth. Another seizure medicine, levetiracetam (Keppra) can now be given this way also. This study will compare IV phenytoin (Dilantin) and IV fosphenytoin to levetiracetam (Keppra) in patients who have had a recent seizure. Only patients with a history of seizures can be involved. The patient must present to the emergency department within 4 hours of a seizure. The purpose of this study is to compare these three drugs, phenytoin (Dilantin), fosphenytoin, and levetiracetam (Keppra). The investigators are looking to see if these drugs can prevent another seizure in the next 24 hours. We are also looking for any possible side effects.
Detailed Description	More than one in every one hundred patients presenting to the emergency department for care do so for seizures. More than half of these patients will require medications, often intravenously (IV), while in the emergency department. For many years the standard treatment has been phenytoin. However, there are many known contraindications to the use of this drug. These include known hypersensitivity, cardiac arrhythmias, cardiac disease, impaired liver or kidney function, diabetes mellitus, older age, thyroid disease, pregnancy, and alcohol use. A recent review of patients with seizure disorder at Emory Crawford Long and Emory University hospitals suggested that a significant percentage of those who were taking phenytoin actually had one or more of these contraindications. Additionally, the IV form of phenytoin has known, severe adverse effects including cardiovascular collapse, life threatening cardiac arrhythmias, and severe hypotension. There is another form of Phenytoin, called Fosphenytoin, that while safer in some respects still has similar concerns associated with its administration. Levetiracetam (Keppra) has been available as an oral drug in the United States since 2000 and has a well established safety record when used as an add-on drug for patients with partial onset seizures. A double-blinded randomized study has shown that levetiracetam is also effective for primary generalized seizures as well. The IV form of levetiracetam has recently been approved by the FDA for use. The only known contraindications other than known hypersensitivity include impaired renal function, psychiatric disorder, older age, and pregnancy. IV levetiracetam is not known to cause any of the acute, catastrophic events seen occasionally with phenytoin. The investigators would therefore like to compare IV phenytoin and fosphenytoin to IV levetiracetam in preventing early recurrent seizures. Patients with known seizure disorders would be randomly assigned to one of two groups and therefore receive either IV fosphenytoin or IV levetiracetam. After an observation period, seizure free patients would be discharged and 24 hour phone follow up conducted to assess for the effectiveness of these anti-seizure medications as well as for any adverse reactions.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Tonic-clonic Seizure
Intervention ICMJE	Drug: Keppra The patient will receive 1 gram of Keppra added to 100ml diluent and will be infused over 15 minutes. Other Name: levetiracetam; Drug: Fosphenytoin IV load will be dependant on dilantin level. If no dilantin is detected in the patient, the patient will receive 1 gram of IV Fosphenytoin infused at 15 mg/min or slower depending on vitals. Other Name: Cerebyx; Drug: Dilantin IV load will be dependant on dilantin level. If no dilantin is detected in the patient, the patient will receive 1 gram of IV phenytoin infused at 25 mg/min or slower depending on vitals. Other Name: phenytoin
Study Arms	Active Comparator: Phenytoin/Fosphenytoin Patients in the control arm will receive either IV Dilantin (1 gram of IV phenytoin infused at 25 mg/min or slower depending on vitals) or IV Fosphenytoin (1 gram of IV Fosphenytoin infused at 15 mg/min or slower depending on vitals). Interventions: Drug: Fosphenytoin Drug: Dilantin; Active Comparator: Levetiracetam Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes). Intervention: Drug: Keppra
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 8, 2008)	158
Original Estimated Enrollment ICMJE; (submitted: July 31, 2007)	188
Actual Study Completion Date	December 2008
Actual Primary Completion Date	December 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: age 18 or older; patient presenting to Grady Memorial Hospital's Emergency Department after having a tonic-clonic seizure (primary or secondarily generalized) within the last 4 hours Cause of seizure for inclusion: reason for seizure is often undetermined at time of presentation to the Emergency Department. The most likely expected causes of a seizure are noncompliance to existing antiepileptic drug regimen, refractory epilepsy with breakthrough seizure, metabolic aberration, alcohol withdrawal, or unknown. Exclusion Criteria: non-English speaking; first time seizure; seizures other than tonic-clonic seizure (primary or secondarily generalized); more than 3 seizures in 24 hours or status epilepticus, pregnant patients by history or by urine pregnancy testing, serious neurologic insult resulting in seizure but where seizure is not the primary reason for admission (e.g. traumatic brain injury with seizure or hemorrhagic stoke would be excluded); contraindication to IV levetiracetam; received IV phenytoin within 24 hours; known allergy to phenytoin; previously enrolled in the study
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00510783
Other Study ID Numbers ICMJE	IRB00002266
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Debra Houry, MD, MPH, Emory University
Study Sponsor ICMJE	Emory University
Collaborators ICMJE	UCB Pharma
Investigators ICMJE	Principal Investigator: Debra Houry, MD Emory University
PRS Account	Emory University
Verification Date	November 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP