Tonic-clonic Seizure
Conditions
Keywords
tonic-clonic seizure, emergency department, IV levetiracetam, Keppra, seizures, phenytoin, Dilantin, Grand Mal seizure
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.
Interventions
DRUGKeppra
The patient will receive 1 gram of Keppra added to 100ml diluent and will be infused over 15 minutes.
DRUGFosphenytoin
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.
DRUGDilantin
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.
Sponsors
UCB Pharma
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Study completed
Pre-assignment details
study completed
Participants by arm
| Arm | Count |
|---|---|
| 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). | 82 |
| Levetiracetam Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes). | 76 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 29 | 25 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Levetiracetam | Phenytoin/Fosphenytoin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants | 80 Participants | 153 Participants |
| Age Continuous | 65.79 years STANDARD_DEVIATION 154.721 | 51.80 years STANDARD_DEVIATION 106.459 | 58.53 years STANDARD_DEVIATION 131.651 |
| Region of Enrollment United States | 76 participants | 82 participants | 158 participants |
| Sex: Female, Male Female | 53 Participants | 56 Participants | 109 Participants |
| Sex: Female, Male Male | 23 Participants | 26 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 82 | 19 / 76 |
| serious Total, serious adverse events | 0 / 82 | 0 / 76 |
Outcome results
Primary
Number of Participants Who Experienced a Recurrent Seizure After Treatment.
Recurrent seizure is defined as a seizure within 24 hours of treatment in the Emergency Department.
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phenytoin/Fosphenytoin | Number of Participants Who Experienced a Recurrent Seizure After Treatment. | 2 participants |
| Levetiracetam | Number of Participants Who Experienced a Recurrent Seizure After Treatment. | 3 participants |