TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation

NCT02056236 | Completed DMC

• 2 other identifiers: NEF-14-18NL46296.044.13
• Study Type: interventional
• Target: 172
• Locations: 2 countries
• Sites: 11

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.

Conditions

Cardiac Arrest; Anoxic Encephalopathy; Status Epilepticus

Keywords

Cardiac arrest; Postanoxic encephalopathy; Electroencephalographic status epilepticus; EEG monitoring; Anti-epileptic drugs

Outcome Measures

Primary Outcomes (1)

• Neurological outcome

  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 Outcomes (1)

• Long term outcome

  12 months

Study Arms (2)

Anti-epileptic drugs

EXPERIMENTAL

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

No anti-epileptic drugs

ACTIVE COMPARATOR

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

Interventions

Anti-epileptic drugs 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.

Also known as: Lorazepam, Midazolam, Fenytoin, Propofol, Levetiracetam, Valproate, Thiopental

Anti-epileptic drugs

No anti-epileptic drugs 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.

No anti-epileptic drugs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (11)

Hôpital Erasme - Université libre de Bruxelles

Brussels, Lenniksebaan 808, 1070, Belgium

Location

Radboud University Medical Center

Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA, Netherlands

Location

Medisch Spectrum Twente

Enschede, Haaksbergerstraat 55, 7513 ER, Netherlands

Location

University Medical Center Groningen

Groningen, Hanzeplein 1, 9700 RB, Netherlands

Location

St. Antonius Hospital

Nieuwegein, Koekoekslaan 1, 3430 EM, Netherlands

Location

Academic Medical Center

Amsterdam, Meibergdreef 9, 1105 AZ, Netherlands

Location

Maasstad Hospital

Rotterdam, South Holland, 3079 DZ, Netherlands

Location

VieCuri Medical Centre

Venlo, Tegelseweg 210, 5912 BL, Netherlands

Location

Rijnstate Hospital

Arnhem, Wagnerlaan 55, 6815 AD, Netherlands

Location

Maastricht UMC+

Maastricht, Netherlands

Location

Canisius-Wilhelmina Hospital

Nijmegen, Netherlands

Location

Related Publications (5)

• 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.

  PMID: 25377067 BACKGROUND

• 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.

  PMID: 38991197 DERIVED

• 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.

  PMID: 35196426 DERIVED

• 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.

  PMID: 26971488 DERIVED

• 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.

  PMID: 26384469 DERIVED

MeSH Terms

Conditions

Heart Arrest; Hypoxia, Brain; Status Epilepticus

Interventions

Lorazepam; Midazolam; Propofol; Levetiracetam; Valproic Acid; Thiopental

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Seizures; Neurologic Manifestations

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Acetamides; Amides; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Pentanoic Acids; Valerates; Fatty Acids, Volatile; Fatty Acids; Lipids; Thiobarbiturates; Barbiturates; Pyrimidinones; Pyrimidines

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

• Barry Ruijter, MD

  University of Twente

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: February 4, 2014
• First Posted: February 5, 2014
• Study Start: April 1, 2014
• Primary Completion: April 24, 2021
• Study Completion: January 24, 2022
• Last Updated: February 21, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (10); BE (1)