TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation

NCT ID: NCT02056236

Last Updated: 2022-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

172 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2022-01-24

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cardiac Arrest Anoxic Encephalopathy Status Epilepticus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Anti-epileptic drugs

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

No anti-epileptic drugs

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

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Lorazepam Midazolam Fenytoin Propofol Levetiracetam Valproate Thiopental

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rijnstate Hospital

OTHER

Sponsor Role collaborator

Medisch Spectrum Twente

OTHER

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role collaborator

St. Antonius Hospital

OTHER

Sponsor Role collaborator

VieCuri Medical Centre

OTHER

Sponsor Role collaborator

Université Libre de Bruxelles

OTHER

Sponsor Role collaborator

Maasstad Hospital

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role collaborator

Canisius-Wilhelmina Hospital

OTHER

Sponsor Role collaborator

University of Twente

OTHER

Sponsor Role lead

Responsible Party

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Jeannette Hofmeijer

MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jeannette Hofmeijer, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Rijnstate Hospital and University of Twente

Michel van Putten, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Medisch Spectrum Twente and University of Twente

Janneke Horn, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Barry Ruijter, MD

Role: STUDY_DIRECTOR

University of Twente

Locations

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Hôpital Erasme - Université libre de Bruxelles

Brussels, Lenniksebaan 808, Belgium

Site Status

Radboud University Medical Center

Nijmegen, Geert Grooteplein-Zuid 10, Netherlands

Site Status

Medisch Spectrum Twente

Enschede, Haaksbergerstraat 55, Netherlands

Site Status

University Medical Center Groningen

Groningen, Hanzeplein 1, Netherlands

Site Status

St. Antonius Hospital

Nieuwegein, Koekoekslaan 1, Netherlands

Site Status

Academic Medical Center

Amsterdam, Meibergdreef 9, Netherlands

Site Status

Maasstad Hospital

Rotterdam, South Holland, Netherlands

Site Status

VieCuri Medical Centre

Venlo, Tegelseweg 210, Netherlands

Site Status

Rijnstate Hospital

Arnhem, Wagnerlaan 55, Netherlands

Site Status

Maastricht UMC+

Maastricht, , Netherlands

Site Status

Canisius-Wilhelmina Hospital

Nijmegen, , Netherlands

Site Status

Countries

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Belgium Netherlands

References

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Ruijter BJ, van Putten MJ, Horn J, Blans MJ, Beishuizen A, van Rootselaar AF, Hofmeijer J; TELSTAR study group. Treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation (TELSTAR): study protocol for a randomized controlled trial. Trials. 2014 Nov 6;15:433. doi: 10.1186/1745-6215-15-433.

Reference Type BACKGROUND
PMID: 25377067 (View on PubMed)

van Putten MJAM, Ruijter BJ, Horn J, van Rootselaar AF, Tromp SC, van Kranen-Mastenbroek V, Gaspard N, Hofmeijer J; TELSTAR Investigators. Quantitative Characterization of Rhythmic and Periodic EEG Patterns in Patients in a Coma After Cardiac Arrest and Association With Outcome. Neurology. 2024 Aug 13;103(3):e209608. doi: 10.1212/WNL.0000000000209608. Epub 2024 Jul 11.

Reference Type DERIVED
PMID: 38991197 (View on PubMed)

Ruijter BJ, Keijzer HM, Tjepkema-Cloostermans MC, Blans MJ, Beishuizen A, Tromp SC, Scholten E, Horn J, van Rootselaar AF, Admiraal MM, van den Bergh WM, Elting JJ, Foudraine NA, Kornips FHM, van Kranen-Mastenbroek VHJM, Rouhl RPW, Thomeer EC, Moudrous W, Nijhuis FAP, Booij SJ, Hoedemaekers CWE, Doorduin J, Taccone FS, van der Palen J, van Putten MJAM, Hofmeijer J; TELSTAR Investigators. Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest. N Engl J Med. 2022 Feb 24;386(8):724-734. doi: 10.1056/NEJMoa2115998.

Reference Type DERIVED
PMID: 35196426 (View on PubMed)

Hofmeijer J, van Putten MJ. EEG in postanoxic coma: Prognostic and diagnostic value. Clin Neurophysiol. 2016 Apr;127(4):2047-55. doi: 10.1016/j.clinph.2016.02.002. Epub 2016 Feb 11.

Reference Type DERIVED
PMID: 26971488 (View on PubMed)

Ruijter BJ, van Putten MJ, Hofmeijer J. Generalized epileptiform discharges in postanoxic encephalopathy: Quantitative characterization in relation to outcome. Epilepsia. 2015 Nov;56(11):1845-54. doi: 10.1111/epi.13202. Epub 2015 Sep 19.

Reference Type DERIVED
PMID: 26384469 (View on PubMed)

Other Identifiers

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NL46296.044.13

Identifier Type: OTHER

Identifier Source: secondary_id

NEF-14-18

Identifier Type: -

Identifier Source: org_study_id

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