Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
132
Countries
1
Sites
13
Convulsive or nonconvulsive benzodiazepine-resistant (established) status epilepticus (eSE) in people 65 years or older
Primary goal is to generate evidence for the treatment of established SE in an elderly population.
Key facts
- Sponsor
- Universitaet Leipzig
- Participant type
- Patients
- Age range
- 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 1 Feb 2024 → ongoing
- Decision date (initial)
- 2024-10-11
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-516634-35-00
- EudraCT number
- 2018-003917-16
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
Primary goal is to generate evidence for the treatment of established SE in an elderly population.
Conditions and MedDRA coding
Convulsive or nonconvulsive benzodiazepine-resistant (established) status epilepticus (eSE) in people 65 years or older
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10041962 | Status epilepticus | 100000004852 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- 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 1
- • 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SCP100375882 · ATC
- Active substance
- Valproate Semisodium
- Substance synonyms
- DIVALPROEX SODIUM
- Route of administration
- INFUSION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 3 g gram(s)
- Max treatment duration
- 1 Month(s)
- Authorisation status
- Authorised
- ATC code
- N03AG01 — VALPROIC ACID
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1053884 · ATC
- Active substance
- Levetiracetam
- Substance synonyms
- S-ETIRACETAM
- Route of administration
- INFUSION
- Max daily dose
- 4.5 g gram(s)
- Max total dose
- 4.5 g gram(s)
- Max treatment duration
- 1 Month(s)
- Authorisation status
- Authorised
- ATC code
- N03AX14 — LEVETIRACETAM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaet Leipzig
- Sponsor organisation
- Universitaet Leipzig
- Address
- Ritterstrasse 26, Zentrum Zentrum
- City
- Leipzig
- Postcode
- 04109
- Country
- Germany
Scientific contact point
- Organisation
- Universitaet Leipzig
- Contact name
- Anett Schmiedeknecht
Public contact point
- Organisation
- Universitaet Leipzig
- Contact name
- Anett Schmiedeknecht
Locations
1 EU/EEA country · 13 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 132 | 13 |
| Rest of world | — | 0 | — |
Investigational sites
Universitaetsklinikum Erlangen AöR
Neurologische Klinik, Schwabachanlage 6, Innenstadt, Erlangen
Universitaetsklinikum Ulm AöR
Klinik für Neurologie, Oberer Eselsberg 45, Eselsberg, Ulm
Universitaetsklinikum Giessen und Marburg GmbH
Klinik für Neurologie, Baldingerstrasse 1, 35043, Marburg
Vivantes Netzwerk fuer Gesundheit GmbH
Klinik für Neurologie, Am Nordgraben 2/1, Wittenau, Berlin
Klinikum Dortmund gGmbH
Klinik für Neurologie, Beurhausstrasse 40, Mitte, Dortmund
Klinikum Kassel GmbH
Klinik für Neurologie, Moenchebergstrasse 41-43, Fasanenhof, Kassel
Evangelische Krankenhausstiftung Oldenburg
Universitätsklinik für Neurologie, Steinweg 13-17, Innenstadt, Oldenburg
Universitaetsmedizin Greifswald KöR
Klinik und Poliklinik für Neurologie, Ferdinand-Sauerbruch-Strasse, 17489, Greifswald
Charite Universitaetsmedizin Berlin KöR
Klinik für Neurologie, Chariteplatz 1, Mitte, Berlin
Carl-von-Basedow-Klinikum Saalekreis gGmbH
Klinik für Neurologie, Weisse Mauer 52, 06217, Merseburg
Klinikum Osnabrueck GmbH
Neurologische Klinik, Am Finkenhuegel 1-3, Westerberg, Osnabrueck
Universitaetsklinikum Essen AöR
Klinik für Neurologie, Hufelandstrasse 55, Holsterhausen, Essen
Universitaet Leipzig
Klinik und Poliklinik für Neurologie, Liebigstrasse 20, Zentrum-Suedost, Leipzig
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2020-08-26 | 2021-02-06 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-51442
- Halt date
- 2023-08-01
- Member states concerned
- Germany
- Publication date
- 2024-10-14
- Reason
- Sponsor decision
- Explanation
- The break in recruitment and treatment became necessary because the requested prolongation of the trial had not yet been approved by the BMBF. For this reason, no new batch of the trial-specific IMPs could be produced and, as a result, no patients could be included and treated in the trial.
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | ToSEE_trial_protocol_p | 1 |
| Recruitment arrangements (for publication) | ToSEE_recruitment | 1 |
| Subject information and informed consent form (for publication) | ToSEE_informed_consent_assess_emergency_situation | 3 |
| Subject information and informed consent form (for publication) | ToSEE_informed_consent_authorized_representative | 5 |
| Subject information and informed consent form (for publication) | ToSEE_informed_consent_patient | 5 |
| Subject information and informed consent form (for publication) | ToSEE_informed_consent_witness_regulation | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | ToSEE_SmPC_Levetiracetam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | ToSEE_SmPC_Orfiril | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-23 | Germany | Acceptable 2024-10-08
|
2024-10-11 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-07-28 | Germany | Acceptable | 2025-08-07 |