To estimate the effect of medical treatment of electro-encephalographic status epilepticus on neurological outcome of patients with postanoxic encephalopathy after cardiac arrest
ID
Source
Brief title
Condition
- Encephalopathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary 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).
Secondary outcome
Secondary outcome measures will include i) mortality; ii) the CPC scores 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)
(Ware and Sherbourne, 1992), vii) depression as measured by the Montgomery and
Åsberg Depression Rating Scale (MADRS) (Montgomery and Asberg, 1979), and viii)
cognitive functioning as measured by detailed neuropsychological examination
after 12 months.
Background summary
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 treatment 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.
Study 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 propose a multicenter clinical trial with randomized treatment allocation,
open label treatment and blinded endpoint evaluation (PROBE design). The
intervention contrast will be medical treatment vs. no treatment of
electroencephalographic status epilepticus, in addition to standard best
medical management of comatose patients after cardiac arrest, including
therapeutic hypothermia.
Intervention
Treatment of electroencephalographic status epilepticus will be based on
international guidelines for treatment of overt status epilepticus. The
objective of the 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.
Study burden and risks
Medical treatment of electroencephalographic status epilepticus may modify the
high risk of death. Otherwise, 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 negligible.
Wagnerlaan 55
Arnhem 6815 AD
NL
Wagnerlaan 55
Arnhem 6815 AD
NL
Listed location countries
Age
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.
*We will use a broad definition of electroencephalographic status epilepticus,
including all epileptiform discharges (spikes, poly spikes, sharp-waves,
sharp-and-slow-wave complexes) at a rate of >= 0.5 Hz, irrespective of their
spatiotemporal evolution, accompanying clinical phenomena, or effects of
anti-epileptic drugs. Rhythmic delta or theta activity will not be included.
For continuous seizure activity, the minimum duration requirement is 30
minutes. Intermittent seizures of 5 minutes and longer, recurring at least
twice, with seizure-free intervals shorter than 60 minutes will also be
included. EEG assessment for inclusion will be left to the discretion of the
treating neurologist or clinical neurophysiologist.
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, for example not living in the
Netherlands
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02056236 |
| CCMO | NL46296.044.13 |