G41.9
Conditions
Interventions
Group 1: valproate 30mg/kg, one single infusion over 10 minutes, Maximum 3g
Group 2: levetiracetam 45 mg/kg, one single infusion over 10 minutes, Maximum 4.5g
Sponsors
Universität Leipzig
Eligibility
Sex/Gender
All
Age
65 Years to No maximum
Inclusion criteria
Inclusion criteria: Adult patients = 65 years old with ongoing convulsive SE (generalized CSE/focal CSE with impaired consciousness/focal CSE without impaired consciousness), as defined by a seizure lasting = 5 minutes or 2 or more convulsive seizures without full recovery of consciousness = 5 minutes, or nonconvulsive SE (NCSE with coma/ NCSE without coma) defined as ongoing EEG patterns consistent with definite or possible NCSE according to the Salzburg criteria (Leitinger et al. 2016), or clinically defined NCSE non-responding to treatment with AT LEAST - Lorazepam 2 mg (i.v.) - Midazolam 5 mg (i.v., buccal, intranasal, i.m.) - Diazepam 5 mg (i.v., rectal) - Clonazepam 1 mg (i.v.)
Exclusion criteria
Exclusion criteria: - Treatment of SE with other antiepileptic drugs/sedatives before enrollment - Intravenous application of VPA or LEV in the last 24 hours before enrollment. - Known or suspected severe liver or pancreatic disease (alcohol addiction, known liver cirrhosis or familial liver diseases, clinical signs of severe liver disease such as ascites, jaundice) - Known concomitant treatment with one or several of the following medications: phenobarbital, phenytoin, carbamazepine, carbapenem antibiotics, rifampicin, erythromycin, cimetidine, primidone, mefloquine, fluoxetine, felbamat, lopinavir, ritonavir - Known coagulopathy (anticoagulants allowed) - Known porphyria, mitochondriopathy and urea cycle disorders - Known severe kidney disease (GFR < 30ml/min) - Hypoglycemia (< 3.3 mmol/l) - Estimated weight < 45kg. - Need for acute neurosurgical treatment. - Known cardiopulmonary resuscitation within the last 7 days before enrollment - Known hypersensitivity against VPA or LEV - Known participation in other interventional trials - Known former participation in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint is the effectiveness of intravenous valproate or levetiracetam to terminate established status epilepticus and maintain control of epileptic activity up to 60 minutes after initiation of the trial intervention. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary goals are to assess the safety profile of valproate and levetiracetam in elderly patients with eSE, and to collect observational data about the established status epilepticus. Key secondary endpoints: - Probability of discontinuing VPA and LEV monotherapies until day 30 after start of the therapy - Time from initiation of trial intervention to cessation of eSE within 60 minutes - Neurological status (including vigilance) 60 minutes after initiation of Intervention - Difference of blood levels of VPA and LEV before and 60 minutes after initiation of intervention - Recurrence of seizures or nonconvulsive/ convulsive SE after initially successful intervention - For patients who failed the primary endpoint, number of patients in whom SE cessated during 60 minutes after initiation of intervention according to the treating physician - For NCSE patients who failed the primary endpoint, time to first cessation, as verified by EEG - Number of patients with SE-associated ventilation until hospital discharge - Functional outcome at discharge, defined by Barthel Index and modified Rankin Scale Assessment of safety: - Mortality - Need for any emergency medication (different from allocated study drug) during 60 minutes after initiation of study intervention - Need for ventilation (noninvasive/ invasive) during 60 minutes after initiation of intervention - Intrahospital complications o Incidence of delirium as diagnosed by the treating physician o Infections requiring intravenous administration of anti-infectives o Adverse events related to infusion/subsequent therapy with antiepileptic drug (sedation, dizziness, nausea, vomiting, thrombocytopenia, leukopenia,hypotension, new elevation of liver enzymes, hyperammonaemia, acute new liver failure or pancreatic damage, tremor, psychiatric abnormalities) | — |
Countries
Germany
Contacts
Public ContactAnett Schmiedeknecht
Zentrum für Klinische Studien Leipzig
Outcome results
None listed