Clinical trial NCT01946776: Cardiac Arrhythmias in Epilepsy: the CARELINK-study
Official title: Cardiac Arrhythmias in Refractory Epilepsy: Identifying Prevalence and LINKage Between Seizures and Arrhythmias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epilepsy
Asystole
Cardiac Arrhythmias
Lead sponsor: Stichting Epilepsie Instellingen Nederland
Sponsor class: OTHER
Collaborators: name: Fonds NutsOhra
name: Medtronic
First posted: 2013-09-20
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Patients with difficult-to-treat epilepsy ("refractory epilepsy") are at high risk of sudden death: sudden unexpected death in epilepsy (SUDEP). Cardiac arrhythmias are one of the possible causes of SUDEP. When monitoring in the hospital setting, the frequency of cardiac arrhythmias in people with epilepsy is low: 0,4%. However, when a subcutaneous implantable device (Reveal XT) is used to monitor heart rhythm continuously for an extended period of time, the frequency of clinically relevant arrhythmias appeared much higher in two small observational studies (n=19): 6-20%. The aim of this study is to analyze the frequency and underlying mechanism of cardiac arrhythmias in a larger group of 50 people with refractory epilepsy with Reveal XT. In the future, this may help us to identify those epilepsy patients at high risk of cardiac arrhythmias, so that we can timely institute preventive measures (e.g. pacemaker implantation).


Eligibility criteria: Inclusion Criteria:

* Drug-resistant focal epilepsy: failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drug (AED) schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom \[16\]
* ≥ 1 complex partial and/or generalized tonic clonic seizure/month as indicated by history taking
* If female, not pregnant
* Aged 18 to 60 years
* Able to undergo the study procedure as judged by the treating physician.

Exclusion Criteria:

* Clinical suspicion of seizure-induced asystole (e.g. seizures with sudden flaccid falls)
* Reveal implantation (either present or in the past)
* Known clinical relevant structural cardiac disease
* Hereditary syndromes that increase the risk of cardiomyopathy (e.g. Marfan's disease)
* ECG findings suggestive of arrhythmias without proper cardiac evaluation to in- or exclude this possibility. According to European Society of Cardiology (ESC) guidelines on syncope the following ECG findings will be used: bifascicular block and other intraventricular conduction abnormalities, asymptomatic inappropriate sinus bradycardia (\<50 bpm), sinoatrial block or sinus pause ≥3s in the absence of negative chronotropic medications, non-sustained VT, pre-exited QRS complexes, prolonged or short QT interval, Brugada pattern, pattern suggestive of arrhythmogenic right ventricular cardiomyopathy.
* Pacemaker
* Use of beta blockers or other anti-arrhythmic/anti-arrhythmogenic medication
* Previous diagnosis of psychogenic non-epileptic seizures
* Patients who live alone and are not able to recall their seizures

Primary outcomes:
measure: Incidence and two-year prevalence of clinically relevant cardiac arrhythmia.
timeFrame: Continuously for two years or until the end-of-battery-life of Reveal XT (this period is expected to last an additional six months on average)
Secondary outcomes:
measure: the number of patients who will have received a permanent pacemaker at the end of this study.
timeFrame: Continuously for two years or until the end-of-battery-life of Reveal XT (this period is expected to last an additional six months on average)
Other outcomes:
measure: The percentage of seizure-related cardiac arrhythmias
timeFrame: Continuously for two years or until the end-of-battery-life of Reveal XT (this period is expected to last an additional six months on average)
measure: The percentage of patients with a cardioinhibitory response to head-up tilt-testing
timeFrame: During one head-up tilt-test (approximate duration 1,5 hours)
Locations:
city: Heerlen
country: Netherlands
facility: Atrium Medical Center
city: Heeze
country: Netherlands
facility: Epilepsy center Kempenhaeghe
city: Hoofddorp
country: Netherlands
facility: Epilepsy Instititute in the Netherlands Foundation (SEIN)
city: Sneek
country: Netherlands
facility: Antonius Hospital
Study officials:
affiliation: SEIN-Epilepsy Institute in the Netherlands Foundation
name: Roland D Thijs, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Surges R, Thijs RD, Tan HL, Sander JW. Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol. 2009 Sep;5(9):492-504. doi: 10.1038/nrneurol.2009.118. Epub 2009 Aug 11.
citation: Schuele SU, Bermeo AC, Alexopoulos AV, Locatelli ER, Burgess RC, Dinner DS, Foldvary-Schaefer N. Video-electrographic and clinical features in patients with ictal asystole. Neurology. 2007 Jul 31;69(5):434-41. doi: 10.1212/01.wnl.0000266595.77885.7f.
citation: Rugg-Gunn FJ, Simister RJ, Squirrell M, Holdright DR, Duncan JS. Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet. 2004 Dec 18-31;364(9452):2212-9. doi: 10.1016/S0140-6736(04)17594-6.
citation: Nei M, Sperling MR, Mintzer S, Ho RT. Long-term cardiac rhythm and repolarization abnormalities in refractory focal and generalized epilepsy. Epilepsia. 2012 Aug;53(8):e137-40. doi: 10.1111/j.1528-1167.2012.03561.x. Epub 2012 Jun 18.
citation: Sevcencu C, Struijk JJ. Autonomic alterations and cardiac changes in epilepsy. Epilepsia. 2010 May;51(5):725-37. doi: 10.1111/j.1528-1167.2009.02479.x. Epub 2010 Jan 7.