Clinical trial NCT02056236: TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation
Official title: TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiac Arrest
Anoxic Encephalopathy
Status Epilepticus
Keywords: Cardiac arrest
Postanoxic encephalopathy
Electroencephalographic status epilepticus
EEG monitoring
Anti-epileptic drugs
Lead sponsor: University of Twente
Sponsor class: OTHER
Collaborators: name: Rijnstate Hospital
name: Medisch Spectrum Twente
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Radboud University Medical Center
name: University Medical Center Groningen
name: St. Antonius Hospital
name: VieCuri Medical Centre
name: Université Libre de Bruxelles
name: Maasstad Hospital
name: Maastricht University Medical Center
name: Canisius-Wilhelmina Hospital
First posted: 2014-02-05
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurological outcome
timeFrame: three months
Secondary outcomes:
measure: Long term outcome
timeFrame: 12 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hôpital Erasme - Université libre de Bruxelles
state: Lenniksebaan 808
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Geert Grooteplein-Zuid 10
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Haaksbergerstraat 55
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
state: Hanzeplein 1
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Koekoekslaan 1
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: Meibergdreef 9
city: Venlo
country: Netherlands
facility: VieCuri Medical Centre
state: Tegelseweg 210
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
state: Wagnerlaan 55
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
state: Zuid-Holland
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Hospital
Study officials:
affiliation: Rijnstate Hospital and University of Twente
name: Jeannette Hofmeijer, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medisch Spectrum Twente and University of Twente
name: Michel van Putten, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Janneke Horn, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Twente
name: Barry Ruijter, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.