Clinical trial • Phase IV • Neurology

Valproate semisodium for Status epilepticus | Benzodiazepine-resistant established status epilepticus

Phase IV trial of Valproate semisodium for Status epilepticus | Benzodiazepine-resistant established status epilepticus.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Status epilepticus | Benzodiazepine-resistant established status epilepticus
Trial Stage
Phase IV
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
23-09-2024
First CTIS Authorization Date
11-10-2024

Trial design

Randomised, intravenous valproate (vpa) versus intravenous levetiracetam (lev); dose/schedule not specified in the available ctis data-controlled Phase IV trial across 13 sites in Germany.

Randomised
Yes
Comparator
Intravenous valproate (VPA) versus intravenous levetiracetam (LEV); dose/schedule not specified in the available CTIS data
Target Sample Size
132

Eligibility

Recruits 132 Elderly patients (≥65 years) selected as a vulnerable population. Informed consent documentation in the submission includes: Subject information and informed consent form (patient), informed consent form for an authorized representative, an informed consent form to assess emergency situations, and a witness regulation form — indicating that consent procedures accommodate incapacitated patients via authorized representatives or emergency procedures..

Vulnerable Population
Elderly patients (≥65 years) selected as a vulnerable population. Informed consent documentation in the submission includes: Subject information and informed consent form (patient), informed consent form for an authorized representative, an informed consent form to assess emergency situations, and a witness regulation form — indicating that consent procedures accommodate incapacitated patients via authorized representatives or emergency procedures.

Inclusion criteria

  • {"criterion_text":"-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 •\tLorazepam 2 mg (i.v.) •\tMidazolam 5 mg (i.v., buccal, intranasal, i.m.) •\tDiazepam 5 mg (i.v., rectal) •\tClonazepam 1 mg (i.v.)"}

Exclusion criteria

  • {"criterion_text":"-Treatment of SE with other antiepileptic drugs/sedatives before enrollment"}
  • {"criterion_text":"-Intravenous application of VPA or LEV in the last 24 hours before enrollment."}
  • {"criterion_text":"-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)"}
  • {"criterion_text":"-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"}
  • {"criterion_text":"-Known coagulopathy (anticoagulants allowed)"}
  • {"criterion_text":"-Known porphyria, mitochondriopathy and urea cycle disorders"}
  • {"criterion_text":"-Known severe kidney disease (GFR < 30ml/min)"}
  • {"criterion_text":"-Hypoglycemia (< 3.3 mmol/l)"}
  • {"criterion_text":"-Estimated weight < 45kg."}
  • {"criterion_text":"-Need for acute neurosurgical treatment."}
  • {"criterion_text":"-Known cardiopulmonary resuscitation within the last 7 days before enrollment"}
  • {"criterion_text":"-Known hypersensitivity against VPA or LEV"}
  • {"criterion_text":"-Known participation in other interventional trials"}
  • {"criterion_text":"-Known former participation in this trial"}

Endpoints

Primary endpoints

  • {"endpoint_text":"-Primary endpoint is the effectiveness of intravenous valproate (VPA) or levetiracetam (LEV) to terminate eSE and maintain control of epileptic activity up to 60 minutes after initiation of the trial intervention","definition_or_measurement_approach":"Effectiveness defined as termination of established status epilepticus and maintenance of control of epileptic activity up to 60 minutes after start of the trial intervention; assessed during the 60-minute post-intervention observation period (clinical assessment and EEG where applicable)."}

Recruitment

Planned Sample Size
132
Recruitment Window Months
69
Consent Approach
Consent obtained from participants where possible (patient informed consent form available). For incapacitated participants there are specific informed consent forms for an authorized representative, procedures to assess emergency situations, and a witness regulation form — indicating consent may be obtained via an authorized representative or emergency/witness procedures. No paediatric assent documents are indicated.

Geography

Total Number Of Sites
13
Total Number Of Participants
132

Germany

Earliest CTIS Part Ii Submission Date
30-09-2024
Latest Decision Or Authorization Date
07-08-2025
Processing Time Days
311
Number Of Sites
13
Number Of Participants
132

Sites

Site Name
Universitaetsmedizin Greifswald KöR
Department Name
Klinik und Poliklinik für Neurologie
Principal Investigator Name
Felix von Podewils
Principal Investigator Email
felix.vonpodewils@med.uni-greifswald.de
Contact Person Name
Felix von Podewils
Site Name
Carl-von-Basedow-Klinikum Saalekreis gGmbH
Department Name
Klinik für Neurologie
Principal Investigator Name
Carsten Hobohm
Principal Investigator Email
neurologie@klinikum-saalekreis.de
Contact Person Name
Carsten Hobohm
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Neurologische Klinik
Principal Investigator Name
Stefan Gerner
Principal Investigator Email
stefan.gerner@uk-erlangen.de
Contact Person Name
Stefan Gerner
Contact Person Email
stefan.gerner@uk-erlangen.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Neurologie
Principal Investigator Name
Felicitas Becker
Principal Investigator Email
felicitas.becker@rku.de
Contact Person Name
Felicitas Becker
Contact Person Email
felicitas.becker@rku.de
Site Name
Klinikum Kassel GmbH
Department Name
Klinik für Neurologie
Principal Investigator Name
Christian Roth
Principal Investigator Email
christian.roth@gnh.net
Contact Person Name
Christian Roth
Contact Person Email
christian.roth@gnh.net
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Neurologie
Principal Investigator Name
Carlos M. Quesada
Principal Investigator Email
carlos.quesada@uk-essen.de
Contact Person Name
Carlos M. Quesada
Contact Person Email
carlos.quesada@uk-essen.de
Site Name
Vivantes Netzwerk fuer Gesundheit GmbH
Department Name
Klinik für Neurologie
Principal Investigator Name
Bettina Schmitz
Principal Investigator Email
bettina.schmitz@vivantes.de
Contact Person Name
Bettina Schmitz
Contact Person Email
bettina.schmitz@vivantes.de
Site Name
Klinikum Osnabrueck GmbH
Department Name
Neurologische Klinik
Principal Investigator Name
Christoph Kellinghaus
Principal Investigator Email
Christoph.Kellinghaus@klinikum-os.de
Contact Person Name
Christoph Kellinghaus
Site Name
Klinikum Dortmund gGmbH
Department Name
Klinik für Neurologie
Principal Investigator Name
Gernot Reimann
Principal Investigator Email
Gernot.Reimann@klinikumdo.de
Contact Person Name
Gernot Reimann
Contact Person Email
Gernot.Reimann@klinikumdo.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Neurologie
Principal Investigator Name
Andreas Meisel
Principal Investigator Email
andreas.meisel@charite.de
Contact Person Name
Andreas Meisel
Contact Person Email
andreas.meisel@charite.de
Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Neurologie
Principal Investigator Name
Johann Pelz
Principal Investigator Email
Johann.Pelz@medizin.uni-leipzig.de
Contact Person Name
Johann Pelz
Site Name
Universitaetsklinikum Giessen und Marburg GmbH
Department Name
Klinik für Neurologie
Principal Investigator Name
Susanne Knake
Principal Investigator Email
knake@med.uni-marburg.de
Contact Person Name
Susanne Knake
Contact Person Email
knake@med.uni-marburg.de
Site Name
Evangelische Krankenhausstiftung Oldenburg
Department Name
Universitätsklinik für Neurologie
Principal Investigator Name
Karsten Witt
Principal Investigator Email
karsten.witt@evangelischeskrankenhaus.de
Contact Person Name
Karsten Witt

Sponsor

Primary sponsor

Full Name
Universitaet Leipzig
Organisation Type
Educational Institution
Country Of Registered Address
Germany

Investigational products

Investigational Product Name
VALPROIC ACID
Active Substance
Valproate semisodium
Modality
Small molecule
Routes Of Administration
Infusion (intravenous)
Route
Intravenous (infusion)
Authorisation Status
SmPC available; marketing authorisation number not provided
Maximum Dose
3 g per day
Investigational Product Name
LEVETIRACETAM
Active Substance
Levetiracetam
Modality
Small molecule
Routes Of Administration
Infusion (intravenous)
Route
Intravenous (infusion)
Authorisation Status
SmPC available; marketing authorisation number not provided
Maximum Dose
4.5 g per day

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