Tonic-clonic SeizurePhase 4NCT00510783
IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures
A Phase 4 study testing Keppra, Fosphenytoin and Dilantin in people with Tonic-clonic Seizure, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tonic-clonic Seizure
- What is being tested?
- Keppra, Fosphenytoin and Dilantin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 158 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Dec 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Tonic-clonic Seizure
- Being tested
- Keppra, Fosphenytoin, Dilantin
- Keywords
- tonic-clonic seizure, emergency department, IV levetiracetam, Keppra, seizures, phenytoin, Dilantin, Grand Mal seizure
- Medical subject headings
- Seizures, Emergencies, Epilepsy, Tonic-Clonic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KeppraDrug
Also called levetiracetam
The patient will receive 1 gram of Keppra added to 100ml diluent and will be infused over 15 minutes.
FosphenytoinDrug
Also called Cerebyx
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.
DilantinDrug
Also called phenytoin
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.
| Study group | Role | What they receive |
|---|---|---|
| Phenytoin/Fosphenytoin | Active comparator | 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). Receives: Drug: Fosphenytoin; Drug: Dilantin |
| Levetiracetam | Active comparator | Patients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes). Receives: Drug: Keppra |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2007 (estimated)
- Study startJul 2007
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tonic-clonic SeizureStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- UCB Pharma
- Responsible party
- Principal investigator, Debra Houry, MD, MPH, Emory University
- Investigators
- Debra Houry, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00510783
- Sponsor's protocol ID
- IRB00002266
- Status last verified
- Nov 2013
- First submitted
- 31 Jul 2007
- Last updated
- 12 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IV Keppra in the Emergency Department for Prevention of Early Recurrent Seizures
- ClinicalTrials.gov ID
- NCT00510783
- Acronym / sponsor ID
- IRB00002266
- Conditions
- Tonic-clonic Seizure
- Keywords
- tonic-clonic seizure, emergency department, IV levetiracetam, Keppra, seizures, phenytoin, Dilantin, Grand Mal seizure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- UCB Pharma
- Study start
- Jul 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 2 Aug 2007 (estimated)
- Results
- Posted 5 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phenytoin/Fosphenytoin | Active comparator | Drug: Fosphenytoin, Drug: DilantinPatients 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). |
| Levetiracetam | Active comparator | Drug: KeppraPatients in the intervention arm will receive IV Keppra (1 gram of Keppra added to 100 mL diluent infused over 15 minutes). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KeppraAlso: levetiracetamThe patient will receive 1 gram of Keppra added to 100ml diluent and will be infused over 15 minutes. | Drug | Levetiracetam |
| FosphenytoinAlso: CerebyxIV 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. | Drug | Phenytoin/Fosphenytoin |
| DilantinAlso: phenytoinIV 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. | Drug | Phenytoin/Fosphenytoin |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Debra Houry, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Keppra, Fosphenytoin and Dilantin in people with Tonic-clonic Seizure, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced a Recurrent Seizure After Treatment. (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2013.