TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation (TELSTAR)

February 3, 2022 updated by: Jeannette Hofmeijer, University of Twente
The purpose of this study is to estimate the effect of medical treatment of electro-encephalographic status epilepticus on neurological outcome of patients with postanoxic encephalopathy after cardiac arrest.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Rationale: Electroencephalographic status epilepticus is described in 9-35% of patients with postanoxic encephalopathy after cardiac arrest and is associated with case fatality rates of 90-100%. It is unclear whether (some) electroencephalographic seizure patterns in these patients represent a condition which can be treated with antiepileptic drugs to improve outcome, or have to be regarded as an expression of severe ischemic damage, in which treatment with antiepileptic would be futile. Therefore, both treatment with and treatment without antiepileptic drugs are considered standard modalities in these patients. We aim to compare these standard strategies and hypothesize that aggressive and early treatment of electro-encephalographic status epilepticus with antiepileptic drugs improves outcome as compared to treatment without these drugs.

Objective: To estimate the effect of medical treatment of electro-encephalographic status epilepticus on neurological outcome of patients with postanoxic encephalopathy after cardiac arrest

Study design: We will perform a multicenter clinical trial with randomized treatment allocation, open label treatment and blinded endpoint evaluation (PROBE design). The intervention contrast will be aggressive medical treatment vs. no treatment of electroencephalographic status epilepticus, in addition to standard best medical management of comatose patients after cardiac arrest, including mild therapeutic hypothermia.

Study population: The study population will consist of adult patients with postanoxic encephalopathy after cardiac arrest, admitted to the intensive care unit, with electroencephalographic status epilepticus on continuous EEG, who are eligile for inclusion in this trial.

Intervention: Treatment of electroencephalographic status epilepticus will be based on guidelines for treatment of overt status epilepticus. The objective of this treatment will be to suppress all epileptiform activity in the EEG. If the electroencephalographic status epilepticus will return after tapering sedative treatment at 24 hours, the procedure will be repeated. If the status will return after 2 x 24 hours, it will be considered refractory.

Main study parameters/endpoints: The primary outcome measure will be neurological outcome defined as the score on the Cerebral Performance Category (CPC) at 3 months dichotomized as good (CPC 1-2 = no or moderate neurological disability) and poor (CPC 3-5 = severe disability, coma, or death).

Sample size: With a presumed reduction of poor outcome of 7%, from 99% - 92%, alpha of 5%, power of 80%, one tailed testing, and one interim analysis by an independent data safety and monitoring board, the objected number of inclusions is 172. With an estimation of an incidence of electroencephalographic status epilepticus of 20% in patients with postanoxic coma, the total number of patients to be monitored will be 860.

Nature and extent of the burden and risks associated with participation: Medical treatment of electroencephalographic status epilepticus may modify the high risk of death. Otherwise, this treatment of electroencephalographic status epilepticus may lead to prolonged hospitalization of several days of comatose patients that otherwise would have died. The risk of an increase of morbidity or mortality on the longer term is considered negligible.

Study Type

Interventional

Enrollment (Actual)

172

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Lenniksebaan 808
      • Brussels, Lenniksebaan 808, Belgium, 1070
        • Hopital Erasme - Universite Libre de Bruxelles
  • Netherlands
      • Maastricht, Netherlands
        • Maastricht UMC+
      • Nijmegen, Netherlands
        • Canisius-Wilhelmina Hospital
    • Geert Grooteplein-Zuid 10
      • Nijmegen, Geert Grooteplein-Zuid 10, Netherlands, 6525 GA
        • Radboud University Medical Center
    • Haaksbergerstraat 55
      • Enschede, Haaksbergerstraat 55, Netherlands, 7513 ER
        • Medisch Spectrum Twente
    • Hanzeplein 1
      • Groningen, Hanzeplein 1, Netherlands, 9700 RB
        • University Medical Center Groningen
    • Koekoekslaan 1
      • Nieuwegein, Koekoekslaan 1, Netherlands, 3430 EM
        • St. Antonius Hospital
    • Meibergdreef 9
      • Amsterdam, Meibergdreef 9, Netherlands, 1105 AZ
        • Academic Medical Center
    • Tegelseweg 210
      • Venlo, Tegelseweg 210, Netherlands, 5912 BL
        • Viecuri Medical Centre
    • Wagnerlaan 55
      • Arnhem, Wagnerlaan 55, Netherlands, 6815 AD
        • Rijnstate Hospital
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
        • Maasstad Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients after cardiac arrest with suspected postanoxic encephalopathy
  • Age 18 years or older
  • Continuous EEG with at least eight electrodes started within 24 hours after cardiac arrest
  • Electroencephalographic status epilepticus on continuous EEG
  • Possibility to start treatment within three hours after detection of electroencephalographic status epilepticus.

Exclusion Criteria:

  • A known history of another medical condition with limited life expectancy (<6 months)
  • Any progressive brain illness, such as a brain tumor or neurodegenerative disease
  • Pre-admission Glasgow Outcome Scale score of 3 or lower
  • Reason other than neurological condition to withdraw treatment
  • Follow-up impossible due to logistic reasons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anti-epileptic drugs

Step 1: Phenytoin (loading dose 15-20 mg/kg iv, maintenance doses 150 mg iv twice per day) PLUS one of the following benzodiazepines (bolus + continuous infusion): lorazepam or midazolam. Benzodiazepine dosing regimes should be based on national and local protocols for status epilepticus treatment

Step 2: Propofol infusion (with a maximum rate of 8 mg/kg/hour) PLUS a second anti-epileptic drug in addition to fenytoin: Option 1: levetiracetam bolus 1500 mg, followed by 1000 mg 2 dd 1 intravenously or Option 2: valproic acid bolus 10-20 mg/kg in 30 min, followed by15 mg/kg/day in 2 dosages intravenously.

Step 3: Thiopental, initial dosage 12,5 mg/kg/hr for the first 6 hours followed by 5 mg/kg/hr for 6 hours. After these loading dosages, treatment should be guided by the EEG pattern.
Drug: Anti-epileptic drugs

Recommendations for the treatment of status epilepticus are based on recent international guidelines for treatment of overt status epilepticus.

The objective of treatment with AED is to suppress all epileptiform activity. There is no clear proof that induction of a burst-suppression pattern is of additional value and induction of burst suppression is therefore not obligate. If the electroencephalographic status epilepticus returns after tapering sedative treatment at 24 hours, the procedure will be repeated. If the status returns after 2 x 24 hours, it will be considered refractory.

Decisions regarding limitation or withdrawal of treatment will be done in accordance with the Dutch guideline "postanoxic coma". Reasons for withdrawal of treatment will be documented.

Other Names:
  • Valproate
  • Lorazepam
  • Midazolam
  • Propofol
  • Fenytoin
  • Levetiracetam
  • Thiopental
Active Comparator: No anti-epileptic drugs

The non-intervention group will be treated conform standard guidelines of treatment of comatose patients after cardiac arrest, but without anti-epileptic drugs or EEG based deep sedation. Treatment to suppress clinical myoclonia or seizures with low dose propofol is left to the discretion of the treating physician.

Decisions regarding limitation or withdrawal of treatment will be done in accordance with the Dutch guideline "postanoxic coma" in both treatment arms. Reasons for withdrawal of treatment will be documented.
Other: No anti-epileptic drugs

The non-intervention group will be treated conform standard guidelines of treatment of comatose patients after cardiac arrest, but without anti-epileptic drugs or EEG based deep sedation. Treatment to suppress clinical myoclonia or seizures with low dose propofol is left to the discretion of the treating physician.

Decisions regarding limitation or withdrawal of treatment will be done in accordance with the Dutch guideline "postanoxic coma". Reasons for withdrawal of treatment will be documented.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurological outcome
Time Frame: three months
The primary outcome measure will be neurological outcome defined as the score on the Cerebral Performance Category (CPC) at 3 months dichotomized as good (CPC 1-2 = no or moderate neurological disability) and poor (CPC 3-5 = severe disability, coma, or death).
three months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Long term outcome
Time Frame: 12 months

Secondary outcome measures will include i) mortality; ii) the CPC score at 6 and 12 months; iii) length of stay on the ICU; iv) duration of mechanical ventilation; v) seizure recurrence within one year; vi) quality of life as measured by the Medical Outcomes Study 36-item short-form health survey (SF36), depression as measured by the Montgomery and Åsberg Depression Rating Scale (MADRS) , and cognitive functioning as measured by detailed neuropsychological examination after 12 months.

Secondary outcome measures in survivors will be collected to thoroughly assess outcome and quality of life of survivors. These outcome measures will not be collected to test between-group differences, since the estimated number of survivors is small.

Furthermore, a limited amount of data on the use of resources will be collected for analysis of cost-effectiveness, including place of residence at one year and admission in hospitals, rehabilitations centers, and nursing homes within the first year.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Twente

Collaborators

Radboud University Medical Center
University Medical Center Groningen
Maastricht University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
St. Antonius Hospital
Rijnstate Hospital
VieCuri Medical Centre
Maasstad Hospital
Université Libre de Bruxelles
Canisius-Wilhelmina Hospital
Medisch Spectrum Twente

Investigators

  • Principal Investigator: Jeannette Hofmeijer, MD PhD, Rijnstate Hospital and University of Twente
  • Principal Investigator: Michel van Putten, MD PhD, Medisch Spectrum Twente and University of Twente
  • Principal Investigator: Janneke Horn, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • Study Director: Barry Ruijter, MD, University of Twente

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

April 24, 2021

Study Completion (Actual)

January 24, 2022

Study Registration Dates

First Submitted

February 4, 2014

First Submitted That Met QC Criteria

February 4, 2014

First Posted (Estimate)

February 5, 2014

Study Record Updates

Last Update Posted (Actual)

February 21, 2022

Last Update Submitted That Met QC Criteria

February 3, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NEF-14-18
  • NL46296.044.13 (Other Identifier: VCMO the Netherlands)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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