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

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00510783
• Collaborator: UCB Pharma (Industry)
• Enrollment: 158
• Location: 1
• Arms: 2
• Duration (Months): 17.1
• Patients Per Site Per Month: 9.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tonic-clonic Seizure	Drug: Keppra; Drug: Fosphenytoin; Drug: Dilantin	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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: 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: 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: levetiracetam

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced a Recurrent Seizure After Treatment. [24 hours]

   Recurrent seizure is defined as a seizure within 24 hours of treatment in the Emergency Department.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Grady Memorial Hospital	Atlanta	Georgia	United States	30303

Sponsors and Collaborators

• Emory University
• UCB Pharma

Investigators

• Principal Investigator: Debra Houry, MD, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Debra Houry, MD, MPH, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT00510783
• Other Study ID Numbers: IRB00002266; NCT00832858
• First Posted: Aug 2, 2007
• Last Update Posted: Dec 12, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Debra Houry, MD, MPH, Professor, Emory University: tonic-clonic seizure; emergency department; IV levetiracetam; Keppra; seizures; phenytoin; Dilantin; Grand Mal seizure
• Additional relevant MeSH terms: Seizures; Emergencies; Phenytoin; Fosphenytoin; Levetiracetam

Study Results

Participant Flow

Recruitment Details	Study completed
Pre-assignment Detail	study completed

Arm/Group Title	Phenytoin/Fosphenytoin	Levetiracetam
Arm/Group Description	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).	Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes).
Period Title: Overall Study
STARTED	82	76
COMPLETED	51	47
NOT COMPLETED	31	29

Baseline Characteristics

Arm/Group Title	Phenytoin/Fosphenytoin	Levetiracetam	Total
Arm/Group Description	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).	Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes).	Total of all reporting groups
Overall Participants	82	76	158
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	80 97.6%	73 96.1%	153 96.8%
>=65 years	2 2.4%	3 3.9%	5 3.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.80 (106.459)	65.79 (154.721)	58.53 (131.651)
Sex: Female, Male (Count of Participants)
Female	56 68.3%	53 69.7%	109 69%
Male	26 31.7%	23 30.3%	49 31%
Region of Enrollment (participants) [Number]
United States	82 100%	76 100%	158 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced a Recurrent Seizure After Treatment.
Description	Recurrent seizure is defined as a seizure within 24 hours of treatment in the Emergency Department.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phenytoin/Fosphenytoin	Levetiracetam
Arm/Group Description	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).	Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes).
Measure Participants	82	76
Number [participants]	2 2.4%	3 3.9%

Adverse Events

Arm/Group Title	Phenytoin/Fosphenytoin		Levetiracetam
Arm/Group Description	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).		Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes).
All Cause Mortality
	Phenytoin/Fosphenytoin		Levetiracetam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Phenytoin/Fosphenytoin		Levetiracetam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	Phenytoin/Fosphenytoin		Levetiracetam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/82 (48.8%)		19/76 (25%)
Investigations
Fatigue	4/82 (4.9%)	4	7/76 (9.2%)	7
Burning at the IV Site	11/82 (13.4%)	15	5/76 (6.6%)	5
Itching	8/82 (9.8%)	8	0/76 (0%)	0
Dizziness	17/82 (20.7%)	17	7/76 (9.2%)	7

Limitations/Caveats

Several patients were lost to follow-up.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.