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

This study has been completed.
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Debra Houry, MD, MPH, Emory University
ClinicalTrials.gov Identifier:
NCT00510783
First received: July 31, 2007
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Tonic-clonic Seizure
Drug: Keppra
Drug: Fosphenytoin
Drug: Dilantin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Number of Participants Who Experienced a Recurrent Seizure After Treatment. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Recurrent seizure is defined as a seizure within 24 hours of treatment in the Emergency Department.


Enrollment: 158
Study Start Date: July 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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 Names:
  • Fosphenytoin
  • 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 Names:
  • Dilantin
  • phenytoin
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).
Drug: Keppra
The patient will receive 1 gram of Keppra added to 100ml diluent and will be infused over 15 minutes.
Other Names:
  • Keppra
  • levetiracetam

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00510783

Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
UCB Pharma
Investigators
Principal Investigator: Debra Houry, MD Emory University
  More Information

No publications provided

Responsible Party: Debra Houry, MD, MPH, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00510783     History of Changes
Obsolete Identifiers: NCT00832858
Other Study ID Numbers: IRB00002266
Study First Received: July 31, 2007
Results First Received: January 8, 2011
Last Updated: November 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
tonic-clonic seizure
emergency department
IV levetiracetam
Keppra
seizures
phenytoin
Dilantin
Grand Mal seizure

Additional relevant MeSH terms:
Emergencies
Seizures
Disease Attributes
Pathologic Processes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Etiracetam
Fosphenytoin
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 16, 2014