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

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ClinicalTrials.gov Identifier: NCT02056236
Recruitment Status : Recruiting
First Posted : February 5, 2014
Last Update Posted : April 19, 2019
Sponsor:
Collaborators:
Rijnstate Hospital
Medisch Spectrum Twente
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Radboud University
University Medical Center Groningen
St. Antonius Hospital
VieCuri Medical Centre
Université Libre de Bruxelles
Maasstad Hospital
Information provided by (Responsible Party):
Jeannette Hofmeijer, University of Twente

Tracking Information
First Submitted Date  ICMJE February 4, 2014
First Posted Date  ICMJE February 5, 2014
Last Update Posted Date April 19, 2019
Study Start Date  ICMJE April 2014
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2014)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2014)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation
Official Title  ICMJE TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiac Arrest
  • Anoxic Encephalopathy
  • Status Epilepticus
Intervention  ICMJE
  • 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:
    • Lorazepam
    • Midazolam
    • Fenytoin
    • Propofol
    • Levetiracetam
    • Valproate
    • Thiopental
  • 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.

Study Arms  ICMJE
  • Experimental: Anti-epileptic drugs

    Step 1. Lorazepam 4 mg iv (initial dosage) titrated up to a maximum of 12 mg/24 hours OR midazolam 10 mg (initial dosage) up to 60 mg/24 hours (in steps of 5 mg/5 minutes) PLUS Fenytoine bolus i.v. 15-20 mg/kg in 30 minutes, followed by 150 mg 2 dd 1, adapted based on serum levels.

    Step 2. Propofol infusion with a maximum 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.

    Intervention: Drug: Anti-epileptic drugs
  • 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.

    Intervention: Other: No anti-epileptic drugs
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 4, 2014)
172
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeannette Hofmeijer, MD PhD 0031-88-0058877 jhofmeijer@rijnstate.nl
Contact: Michel van Putten, MD PhD 0031-53-4872810 m.j.a.m.vanputten@utwente.nl
Listed Location Countries  ICMJE Belgium,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02056236
Other Study ID Numbers  ICMJE NEF-14-18
NL46296.044.13 ( Other Identifier: VCMO the Netherlands )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jeannette Hofmeijer, University of Twente
Study Sponsor  ICMJE University of Twente
Collaborators  ICMJE
  • Rijnstate Hospital
  • Medisch Spectrum Twente
  • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • Radboud University
  • University Medical Center Groningen
  • St. Antonius Hospital
  • VieCuri Medical Centre
  • Université Libre de Bruxelles
  • Maasstad Hospital
Investigators  ICMJE
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
PRS Account University of Twente
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP