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

• ClinicalTrials.gov Identifier: NCT00510783
• Recruitment Status: Completed
• First Posted: August 2, 2007
• Results First Posted: August 5, 2013
• Last Update Posted: December 12, 2013
• Sponsor: Emory University
• Collaborator: UCB Pharma
• Information provided by (Responsible Party): Debra Houry, MD, MPH, Emory University

Tracking Information

• First Submitted Date: July 31, 2007
• First Posted Date: 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: July 2007
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Tonic-clonic Seizure

Intervention

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 8, 2008): 158
• Original Estimated Enrollment (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

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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00510783
• Other Study ID Numbers: IRB00002266
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Debra Houry, MD, MPH, Emory University
• Original Responsible Party: Not Provided
• Current Study Sponsor: Emory University
• Original Study Sponsor: Same as current
• Collaborators: UCB Pharma

Investigators

• Principal Investigator: Debra Houry, MD; Emory University

• PRS Account: Emory University
• Verification Date: November 2013