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Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial) (FAST)

Primary Purpose

Non-Convulsive Status Epilepticus

Status
Recruiting
Phase
Phase 3
Locations
Denmark
Study Type
Interventional
Intervention
Rapid sedation
Sponsored by
University of Southern Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Convulsive Status Epilepticus

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients (older than 18 years) with EEG-verified NCSE, according to the Salzburg criteria, who have not responded to appropriate treatment with benzodiazepines and at least one 2nd line i.v. anti-seizure medication according to the current Danish national neurological treatment guidelines (Levetiracetam, Fosfenytoin or Valproate).

Exclusion Criteria:

  • patients with epilepticus status due to acute neuroinfection (e.g. bacterial meningitis or viral encephalitis)
  • acute traumatic or spontaneous intracranial hemorrhage
  • suspicion of cerebral anoxia / hypoxia / hypoglycemia / epileptic encephalopathy
  • contraindications to anti-seizure medication defined in the protocol
  • contraindications to anesthesia treatment in intensive care
  • focal motor status epilepticus without relevant conscious influence (Glasgow Coma Scale> 13)
  • known epileptic encephalopathy
  • Clinical need for acute intubation

Sites / Locations

  • Aarhus Universitetshospital
  • Rigshospitalet
  • Odense University HospitalRecruiting
  • University Hospital of ZealandRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

"Non-sedative medical treatment"

Fast sedation

Arm Description

The patient is treated with an additional high-dose intravenous antiepileptic drug, which is selected by the treating neurologist. If NCSE continues to be detected at cEEG or clinically> 3 hours after starting treatment, the patient should receive standard treatment (i.e. sedation in the intensive care unit or addition of additional intravenous antiepileptic drugs) in accordance with local guidelines and the assessment of the treating neurologist. The following preparations are permitted as additional treatment: Levetiracetam (60 mg / kg as saturation dose followed by maintenance dose of 2-4 g / day), valproate (60 mg / kg as saturation dose followed by maintenance dose of 20 mg / kg / day), phosphenytoin (20 PE as saturation dose followed by maintenance dose 5 mg PE / kg / day), lacosamide (400 mg as a saturation dose followed by a maintenance dose of 200-400 mg / day), topiramate (200-400 mg per probe as a saturation dose followed by a maintenance dose of 200-400 mg / day).

Within a maximum of 60 minutes after the diagnosis of NCSE (EEG or clinical), the patient must be sedated with high-dose Propofol (bolus 3-5 g / kg, maintenance dose 5-10 mg / kg / hour) to - 5 on the Richmond agitation sedation scale (RASS) for 20 hours, and a single anti-epileptic drug should be added as adjunctive therapy. Addition of low-dose Midazolam (max. 0.1 mg / kg / h) is permitted if deep sedation (defined clinically by RASS -5) is not possible with Propofol alone. After 20 hours, the sedation should be completely phased out within 3 hours.

Outcomes

Primary Outcome Measures

Proportion of patients with continued NCSE on EEG after 24 h ("treatment failure")
NCSE diagnosed using EEG and defined by the "Salzburg criteria" for NCSE (e.g. Leitinger et al. Lancet Neurology, 2016)

Secondary Outcome Measures

Number of treatment related complications
e.g. tracheostoma, infections
New neurological deficit
Neurological deficits are quantified using National Institute of Health Stroke Scale (NIHSS, maximum possible score is 42, the minimum score - indicating no deficits - is 0) at admission and discharge. New neurological deficit is defined as increase of NIHSS >5 at discharge

Full Information

First Posted
January 17, 2022
Last Updated
June 20, 2023
Sponsor
University of Southern Denmark
Collaborators
Aarhus University Hospital, University Hospital of Zealand, Copenhagen University Hospital, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT05263674
Brief Title
Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)
Acronym
FAST
Official Title
Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 7, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern Denmark
Collaborators
Aarhus University Hospital, University Hospital of Zealand, Copenhagen University Hospital, Denmark

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This open-label, randomized multicenter trial aims at clarifying the standard of care of patients with non-convulsive status epilepticus not responding to treatment with benzodiazepines and at least one high-dose intra venous anti-seizure medication.
Detailed Description
Persistent epileptic seizures, aka. status epilepticus (SE), are the second most common neurological cause of acute admissions. Around halv of the patients suffers from SE without prominent visible seizures ("convulsions"), which is referred to as non-convulsive status epilepticus (NCSE) and is afflicted with a long-term mortality of >50% also in patients without concomittant acute brain disease. There are no evidence-based treatment guidelines for NCSE but patients usually receive treatment with benzodiazepines followed by i.v. anti-seizure medication. If seizures continues, further treatment is controversial. The participating centers have long-standing experience in treating NCSE but use different, internationally accepted treatment strategies. Some initiate aggressive treatment with fast sedation at intensive care aiming at immediate seizure control, other estimate that the side effects of sediation does not outweigh the potential benefit and try high-dose i.v. anti-seizure medication that only slightly impair conciousness - often with success. This randomized, open label, multicenter trial (Eudract 2021-003392-34) aims at clarifying the treatment of patients with NSCE not responding to standard therapy. Patients with verified NCSE based on clinical parameter or using electroencephalography (EEG) are randomized into a fast acute sedation group and a group that receives at least one additional, high-dose anti-seizure mediciation. Primary objective endpoint is treatment failure 24 h after randomization as determined by EEG. Secondary endpoints are e.g. seizure-induced neurological damage, treatment-related complications and neurological long-term outcome. The statistical planing aims at showing superiority of aggressive treatment, 140 patients shall be included in a three years period at the University Hospitals in Aarhus, Odense, Roskilde and Copenhagen.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Convulsive Status Epilepticus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Comparison of two treatment strategies
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
"Non-sedative medical treatment"
Arm Type
No Intervention
Arm Description
The patient is treated with an additional high-dose intravenous antiepileptic drug, which is selected by the treating neurologist. If NCSE continues to be detected at cEEG or clinically> 3 hours after starting treatment, the patient should receive standard treatment (i.e. sedation in the intensive care unit or addition of additional intravenous antiepileptic drugs) in accordance with local guidelines and the assessment of the treating neurologist. The following preparations are permitted as additional treatment: Levetiracetam (60 mg / kg as saturation dose followed by maintenance dose of 2-4 g / day), valproate (60 mg / kg as saturation dose followed by maintenance dose of 20 mg / kg / day), phosphenytoin (20 PE as saturation dose followed by maintenance dose 5 mg PE / kg / day), lacosamide (400 mg as a saturation dose followed by a maintenance dose of 200-400 mg / day), topiramate (200-400 mg per probe as a saturation dose followed by a maintenance dose of 200-400 mg / day).
Arm Title
Fast sedation
Arm Type
Experimental
Arm Description
Within a maximum of 60 minutes after the diagnosis of NCSE (EEG or clinical), the patient must be sedated with high-dose Propofol (bolus 3-5 g / kg, maintenance dose 5-10 mg / kg / hour) to - 5 on the Richmond agitation sedation scale (RASS) for 20 hours, and a single anti-epileptic drug should be added as adjunctive therapy. Addition of low-dose Midazolam (max. 0.1 mg / kg / h) is permitted if deep sedation (defined clinically by RASS -5) is not possible with Propofol alone. After 20 hours, the sedation should be completely phased out within 3 hours.
Intervention Type
Drug
Intervention Name(s)
Rapid sedation
Intervention Description
High-dose Propofol (bolus 3-5 g / kg, maintenance dose 5-10 mg / kg / hour) to - 5 on the Richmond agitation sedation scale (RASS) for 20 hours, and a single anti-epileptic drug should be added as adjunctive therapy. Addition of low-dose Midazolam (max. 0.1 mg / kg / h) is permitted if deep sedation (defined clinically by RASS -5) is not possible with Propofol alone.
Primary Outcome Measure Information:
Title
Proportion of patients with continued NCSE on EEG after 24 h ("treatment failure")
Description
NCSE diagnosed using EEG and defined by the "Salzburg criteria" for NCSE (e.g. Leitinger et al. Lancet Neurology, 2016)
Time Frame
24 hours after randomisation
Secondary Outcome Measure Information:
Title
Number of treatment related complications
Description
e.g. tracheostoma, infections
Time Frame
at discharge, on average after 7 days
Title
New neurological deficit
Description
Neurological deficits are quantified using National Institute of Health Stroke Scale (NIHSS, maximum possible score is 42, the minimum score - indicating no deficits - is 0) at admission and discharge. New neurological deficit is defined as increase of NIHSS >5 at discharge
Time Frame
at discharge, on average after 7 days
Other Pre-specified Outcome Measures:
Title
Influence of cEEG on new neurological deficit
Description
Patients receive either cEEG or spot EEG depending on the center. In this pre-specified analyses, the impact of cEEG vs. spot-EEG on the degree of new neurological deficits (outcome 3) will be compared
Time Frame
at discharge, on average after 7 days
Title
Duration of intensive care treatment
Description
Definition: Time from intubation to discharge from ICU
Time Frame
at discharge, on average after 7 days
Title
Duration of hospitalization
Description
Time from randomization to discharge from hospital in charge for acute treatment of NCSE
Time Frame
1-100 days, on average 7 days
Title
Proportion of patients with superrefractory status epilepticus
Description
Proportion of patients that develop superrefractory status epilepticus after randomization but during current hospitalization
Time Frame
at discharge, on average after 7 days
Title
Survival after discharge
Description
Determined at ambulatory control 3,6,12 and 24 months after randomization
Time Frame
3, 6, 12, and 24 months after randomization
Title
Quality of life after discharge
Description
Determined using questionnaire/patient survey (Quality of Life in Epilepsy Inventory, Qolie-31 Danish translation), at ambulatory controls 3, 6, 12, and 24 months after randomization
Time Frame
3, 6, 12, and 24 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients (older than 18 years) with EEG-verified NCSE, according to the Salzburg criteria, who have not responded to appropriate treatment with benzodiazepines and at least one 2nd line i.v. anti-seizure medication according to the current Danish national neurological treatment guidelines (Levetiracetam, Fosfenytoin or Valproate). Exclusion Criteria: patients with epilepticus status due to acute neuroinfection (e.g. bacterial meningitis or viral encephalitis) acute traumatic or spontaneous intracranial hemorrhage suspicion of cerebral anoxia / hypoxia / hypoglycemia / epileptic encephalopathy contraindications to anti-seizure medication defined in the protocol contraindications to anesthesia treatment in intensive care focal motor status epilepticus without relevant conscious influence (Glasgow Coma Scale> 13) known epileptic encephalopathy Clinical need for acute intubation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christoph P. Beier, M.D.
Phone
+4565411943
Email
cbeier@health.sdu.dk
Facility Information:
Facility Name
Aarhus Universitetshospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Active, not recruiting
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Active, not recruiting
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Beier, M.D.
Email
cbeier@health.sdu.dk
Facility Name
University Hospital of Zealand
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henning P. Hansen, M.D. Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Anonymized IPD will be shared upon reasonable request within the limits of Danish legislation for data security.

Learn more about this trial

Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)

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