Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
154
Countries
1
Sites
5
Status epilepticus
At bestemme virkningen af hurtig sedering med propofol/midazolam på intensiv afdeling sammenlignet med intravenøs anti-epileptisk behandling på sengeafsnit hos patienter med refraktær NKSE.
Key facts
- Sponsor
- Odense University Hospital
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 9 Oct 2024 → ongoing
- Decision date (initial)
- 2024-09-13
- Transition trial
- Yes
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Danske Regioner
External identifiers
- EU CT number
- 2024-515507-18-00
- EudraCT number
- 2021-003392-34
- ClinicalTrials.gov
- NCT05263674
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
At bestemme virkningen af hurtig sedering med propofol/midazolam på intensiv afdeling sammenlignet med intravenøs anti-epileptisk behandling på sengeafsnit hos patienter med refraktær NKSE.
Secondary objectives 5
- At sammenligne akutte bivirkninger af de to behandlingsmodaliteter
- At sammenligne effekten af de to behandlingsmodaliteter på nytilkommet neurologisk skade
- Analyse af indflydelse af cEEG-behandling på behandlingsforløb (gennemføres på Aarhus Universitetshospital og på Rigshospitalet)
- Indflydelse af behandling på mortaliteten og på behandlingsrelaterede komplikationer til behandling (nosokomiale infektioner, tracheostomi rate, dødelighed under indlæggelsen, efter 30 dage, efter 1 og 2 år)
- Økonomiske analyser (indlæggelsestid, tid på intensiv afdeling)
Conditions and MedDRA coding
Status epilepticus
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10041964 | Status epilepticus petit mal | 10029205 |
| 26.1 | LLT | 10057770 | Complex partial status epilepticus | 10029205 |
| 21.1 | LLT | 10057769 | Nonconvulsive status epilepticus | 10029205 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Voksne patienter (ældre end 18 år)
- med eeg-verificeret NKSE jf. Salzburg kriterierne eller patienter, som klinisk har en entydig status epilepticus med mindre motoriske fænomener efter et generaliseret tonisk/klonisk anfald (definition jf. de gældende retningslinjerne svarende til ’status epilepticus without prominent motor symptoms’)
- som har ikke responderet på relevant behandling med benzodiazepiner og mindst et 2. linje i.v. anti-epileptisk præparat jf. den gældende nationale neurologiske behandlingsvejledning (Levetiracetam, Fosfenytoin eller Valproat).
Exclusion criteria 8
- patienter med status epilepticus på grund af akut neuroinfektion (for eksempel bakteriel meningit eller viral encephalit)
- akutte traumatiske eller spontane intrakranielle blødninger mindre end 3 dage før start af NKSE (ved SAH mindre end 14 dage før debut af NCSE).
- mistanke på cerebral anoksi/hypoksi/hypoglykæmi/epileptisk encephalopati
- kontraindikationer til anti-epileptisk behandling jf. de gældende nationale neurologiske behandlingsvejledninger for behandling af NKSE (https://neuro.dk/wordpress/nnbv/)
- kontraindikationer til narkose behandling på intensiv
- fokal motorisk status epilepticus uden relevant bevidsthedspåvirkning (Glasgow Coma Scale >13)
- kendt epileptisk encephalopati
- Klinisk behøv for akut intubation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Antallet af patienter med forsat NKSE efter 24 timer i de to grupper (“treatment failure”).
Secondary endpoints 10
- Ny neurologisk deficit ved udskrivelse fra afdelingen (eller overflytning til en anden hospitalsafdeling), som har gennemført akutbehandlingen. Neurologisk status vurderes ved brug af National Institute of Health Stroke Scale (NIHSS). Neurologisk status forud NKSE estimeres på basis af de foreliggende oplysninger i patientjournalen.
- Indflydelsen af cEEG på nye neurologiske deficits (varigheden af NKSE hos patienter med og uden cEEG).
- Indlæggelsestid
- Død under indlæggelsen
- Tid på intensiv afdeling
- Antal af infektioner under indlæggelsen (defineret som klinisk eller radiologisk diagnose OG opstart af anti-biotisk relevant behandling)
- Forværring af modfied Rankin score indeks ved udskrivelsen
- Antal af patienter med superrefraktær status epilepticus
- Overlevelsen efter 3, 6, 12 og 24 måneder efter randomisering
- Livskvalitet efter udskrivelsen
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 6
SUB08459MIG · Substance
- Active substance
- Levetiracetam
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 60 mg/kg/h milligram(s)/kilogram/hour
- Max total dose
- 1440 mg/kg/h milligram(s)/kilogram/hour
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB11190MIG · Substance
- Active substance
- Topiramate
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Max daily dose
- 600 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25397 · Substance
- Active substance
- Brivaracetam
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB25407 · Substance
- Active substance
- Lacosamide
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12318MIG · Substance
- Active substance
- Sodium Valproate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 40 mg/Kg milligram(s)/kilogram
- Max total dose
- 60 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB13919MIG · Substance
- Active substance
- Fosphenytoin Sodium
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2000 mg milligram(s)
- Max total dose
- 2000 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 2
SUB10116MIG · Substance
- Active substance
- Propofol
- Pharmaceutical form
- EMULSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 240 mg/kg/h milligram(s)/kilogram/hour
- Max total dose
- 240 mg/kg/h milligram(s)/kilogram/hour
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08950MIG · Substance
- Active substance
- Midazolam
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 mg/kg/h milligram(s)/kilogram/hour
- Max total dose
- 12 mg/kg/h milligram(s)/kilogram/hour
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Odense University Hospital
- Sponsor organisation
- Odense University Hospital
- Address
- J B Winsloews Vej 4
- City
- Odense C
- Postcode
- 5000
- Country
- Denmark
Scientific contact point
- Organisation
- Odense University Hospital
- Contact name
- Christoph P. Beier
Public contact point
- Organisation
- Odense University Hospital
- Contact name
- Christoph P. Beier
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Odense University Hospital ORG-100007716
|
Odense C, Denmark | On site monitoring, E-data capture, Code 8 |
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 154 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Herlev Hospital
Neurology, Borgmester Ib Juuls Vej 1, 2730, Herlev
Odense University Hospital
Department of neurology, J B Winsloews Vej 4, 5000, Odense C
Aarhus Universitetshospital
Department of neurology, J120, Palle Juul-Jensens Boulevard 165, Aarhus N
Region Sjaelland
Neurology, Vestermarksvej 6, 4000, Roskilde
Rigshospitalet
Department of neurology, Blegdamsvej 9, 2100, Copenhagen Oe
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 |
|---|---|---|---|---|---|
| Denmark | 2024-10-09 | 2024-10-09 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 16 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_protocol_2024-515507-18-00 | 1.9 |
| Recruitment arrangements (for publication) | Placeholder document | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_patient | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_relative | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS_patient | 1.51 |
| Subject information and informed consent form (for publication) | L1_SIS_patient_TC | 1 |
| Subject information and informed consent form (for publication) | L1_SIS_relative | 1.51 |
| Subject information and informed consent form (for publication) | L1_SIS_relative_dead_pt | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Brivaracetam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Fosphenytoin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Lacosamide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Levetiracetam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Midazolam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Propofol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Topiramate | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Valproat | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-20 | Denmark | Acceptable 2024-09-13
|
2024-09-13 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-10-09 | Denmark | Acceptable 2024-12-04
|
2024-12-04 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-06-19 | Denmark | Acceptable 2024-12-04
|
2025-06-19 |
| 4 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-12-17 | Denmark | Acceptable 2026-01-30
|
2026-01-30 |