Trial document




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  DRKS00022308

Trial Description

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Title

Treatment of Established Status Epilepticus in the Elderly - a prospective, randomized, double-blind comparative effectiveness trial

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Trial Acronym

ToSEE

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URL of the Trial

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Brief Summary in Lay Language

The study ToSEE aims to generate evidence for the treatment of the benzodiazepine-resistant (established) status epilepticus in the elderly. All subtypes of status epilepticus will be considered. The efficacy of the two frequently used drugs levetiracetam and valproat will be compared. Also the safety profile of both drugs will be investigated. ToSEE will also collect information about this disease, its complications and outcome aspects at the time of discharge or 30 days after inclusion at the latest.

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Brief Summary in Scientific Language

ToSEE is a prospective, multicenter, double-blind phase IV-trial with two treatment arms (levetiracetam and valproate) for the therapy of the benzodiazepine- resistant (established)status epilepticus (BRSE) in the elderly. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam (LEV) or valproate (VPA). All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. The Intervention is deemed successful if there is a stable cessation of ictal activity 15 minutes after the start of infusion persisting for the following 45 minutes of observation. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest.

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Do you plan to share individual participant data with other researchers?

No

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00022308
  •   2020/07/03
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  •   yes
  •   Approved
  •   153/19-ff, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

  •   2018-003917-16 
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Health Condition or Problem studied

  •   G41.9 -  Status epilepticus, unspecified
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Interventions/Observational Groups

  •   valproate 30mg/kg, one single infusion over 10 minutes, Maximum 3g
  •   levetiracetam 45 mg/kg, one single infusion over 10 minutes, Maximum 4.5g
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   IV
  •   No
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Primary Outcome

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.

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Secondary Outcome

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:
- 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)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Planned
  •   2021/01/31
  •   477
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   65   Years
  •   no maximum age
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Additional 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.)

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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)
- Known insulin dependent diabetes mellitus
- 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

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Addresses

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    • Universität Leipzig
    • Ritterstraße 26
    • 04109  Leipzig
    • Germany
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    • Klinik und Poliklinik für Neurologie Universitätsklinikum Leipzig
    • Mr.  Prof. Dr. med.  Joseph  Claßen 
    • Liebigstraße 20
    • 04103  Leipzig
    • Germany
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    • Klinik und Poliklinik für NeurologieUniversitätsklinikum Leipzig
    • Ms.  Dr. med.  Annekatrin  Müller 
    • Liebigstraße 20
    • 04103  Leipzig
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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