Ignite Creation Date:
2024-05-05 @ 7:05 PM
Last Modification Date:
2024-10-26 @ 9:43 AM
Study NCT ID:
NCT00603135
Status:
WITHDRAWN
Last Update Posted:
2015-03-10
First Post:
2007-11-13
Brief Title:
Intravenous Levetiracetam as First-line Anticonvulsive Treatment in Patients With Non-convulsive Status Epilepticus
Sponsor:
University Hospital Basel Switzerland
Organization:
University Hospital Basel Switzerland
Study Overview
Official Title:
Intravenous Levetiracetam as First-line Anticonvulsive Treatment in Patients With Non-convulsive Status Epilepticus
Status:
WITHDRAWN
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Keppra
Brief Summary:
Status epilepticus SE represents the most common life-threatening neurological emergency requiring treatment on an intensive care unit The incidence in Western European countries is about 12-18100000 Immediate and effective treatment of SE is obviously essential because of the deleterious effects of continuous seizures on the brain and the whole organism Guidelines emphasize the use of benzodiazepines BZD as first-line anticonvulsive drugs Alternatively iv Phenytoin PHE fosphenytoin FOS and valproate VPA were also tested as first-line anticonvulsants in SE Direct comparison of PHE with lorazepam LZP showed significant superiority of LZP evidence class I Other trials iv PHE or -VPA are of evidence class III or IV BZD VPA and PHE have clinical and pharmacological disadvantages BZD may cause respiratory depression or sedation and may be not suitable for patients with COPD or ambiguous in patients with BZD addiction Some compounds also may induce tachyphylaxis or accumulate under concomitant renal failure PHE has saturable metabolism subject to Michaelis-Menten kinetics increasing the risk of overdosing in an acute setting causing liver damage serious cardiac arrhythmias hypotension cerebellar degeneration peripheral neuropathy and localsystemic skin reactions Although of unequivocal efficacy PHE should no longer be used for long-term because of its adverse effects after chronic administration irreversible cerebellar degeneration causing debilitating ataxia painful polyneuropathy and osteopenia increasing the risk of fractures Metabolism by and self-induction of the hepatic CYP450 system make PHE prone to interactions with several other drugs notably other antiepileptics VPA may cause liver failure hemorrhagic complications pancreatitis and hyperammonemic encephalopathy To summarize these three first-line agents for the treatment of SE may cause serious side effects in several patients with SE
Levetiracetam LEV is broad-spectrum antiepileptic drug It binds to the presynaptic vesicular protein 2A abundantly present in different regions of the brain LEV presynaptically modulates transmitter release but the exact mechanisms remain unclear Data also revealed that LEV stabilizes GABAA receptors upon repetitive activation what is important in treatment of SE because GABAA receptors undergo significant changes of subunit conformation within minutes after sustained activation like during SE These changes render GABAA receptors the less anticonvulsive the longer SE lasts Levetiracetam has a favorable pharmacological profile with large safety margins Its partly extrahepatic hydrolyzation bypasses the CYP450 system renal excretion is 60-70 unchanged and 23-27 metabolized Dosage needs adjustment when renal function is impaired LEV lacks interactions with any drugs yet Drowsiness is the most common side-effect while respiration liver and kidney function and the blood system are not affected LEV shows an important clinical effect even after the first dose and maximal efficacy within the first week of drug-intake The favorable clinico-pharmacological profile predilects LEV for the first-line treatment of SE especially in patients with multi-organ failure sepsis coma etc About 10 of comatous patients may be in non-convulsive SE NCSE on ICUs These patients are under polymedication whereby interactions of the anticonvulsants approved yet for the treatment of NCSE with their other drugs may have fatal effects Conversely non-interacting anticonvulsants would represent an advantage for the treatment of NCSE for these patients
Recently the iv formulation of LEV was approved by the FDA for the use in patients but not specifically for the treatment of SE Data about the single-dose bioavailability of iv-LEV in comparison to oral tablets as well as multiple-dose pharmacokinetics and tolerability in healthy subjects were recently published In addition the administration of iv-LEV dosages ranging from 2000-4000 mg within 15 minutes and of dosages ranging from 1500-2500 mg within 5 minutes was safe and well tolerated and led to efficacious drug levels in a randomized single-blind placebo-controlled safety and pharmacokinetic study in healthy volunteers
Slight somnolence is expected to be the only adverse effect of iv LEV sharply contrasting with the sedation up to coma after iv benzodiazepines Thus even severely ill patients will be accessible to neurological tests under LEV which is a big advantage in this clinical difficult setting of NCSE
I-v LEV is considered an ideal candidate for the first-line use before benzodiazepines in patients with NCSE especially in those with important comorbidity and concomitant polymedication Thus we would like to test the feasibility safety and efficacy of iv-LEV as first-line medication in a open-label single-center prospective pilot study as outlined below
Levetiracetam LEV is broad-spectrum antiepileptic drug It binds to the presynaptic vesicular protein 2A abundantly present in different regions of the brain LEV presynaptically modulates transmitter release but the exact mechanisms remain unclear Data also revealed that LEV stabilizes GABAA receptors upon repetitive activation what is important in treatment of SE because GABAA receptors undergo significant changes of subunit conformation within minutes after sustained activation like during SE These changes render GABAA receptors the less anticonvulsive the longer SE lasts Levetiracetam has a favorable pharmacological profile with large safety margins Its partly extrahepatic hydrolyzation bypasses the CYP450 system renal excretion is 60-70 unchanged and 23-27 metabolized Dosage needs adjustment when renal function is impaired LEV lacks interactions with any drugs yet Drowsiness is the most common side-effect while respiration liver and kidney function and the blood system are not affected LEV shows an important clinical effect even after the first dose and maximal efficacy within the first week of drug-intake The favorable clinico-pharmacological profile predilects LEV for the first-line treatment of SE especially in patients with multi-organ failure sepsis coma etc About 10 of comatous patients may be in non-convulsive SE NCSE on ICUs These patients are under polymedication whereby interactions of the anticonvulsants approved yet for the treatment of NCSE with their other drugs may have fatal effects Conversely non-interacting anticonvulsants would represent an advantage for the treatment of NCSE for these patients
Recently the iv formulation of LEV was approved by the FDA for the use in patients but not specifically for the treatment of SE Data about the single-dose bioavailability of iv-LEV in comparison to oral tablets as well as multiple-dose pharmacokinetics and tolerability in healthy subjects were recently published In addition the administration of iv-LEV dosages ranging from 2000-4000 mg within 15 minutes and of dosages ranging from 1500-2500 mg within 5 minutes was safe and well tolerated and led to efficacious drug levels in a randomized single-blind placebo-controlled safety and pharmacokinetic study in healthy volunteers
Slight somnolence is expected to be the only adverse effect of iv LEV sharply contrasting with the sedation up to coma after iv benzodiazepines Thus even severely ill patients will be accessible to neurological tests under LEV which is a big advantage in this clinical difficult setting of NCSE
I-v LEV is considered an ideal candidate for the first-line use before benzodiazepines in patients with NCSE especially in those with important comorbidity and concomitant polymedication Thus we would like to test the feasibility safety and efficacy of iv-LEV as first-line medication in a open-label single-center prospective pilot study as outlined below
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EKBB 27227 | None | None | None |