Cardiac Arrhythmias in Epilepsy: the CARELINK-study

Epilepsy Clinical Trial

— CARELINK  

Official title:

Cardiac Arrhythmias in Refractory Epilepsy: Identifying Prevalence and LINKage Between Seizures and Arrhythmias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01946776
• Other study ID #: 1201-071
• Status: Completed
• Phase: N/A
• First received: August 29, 2013
• Last updated: December 23, 2016
• Start date: June 2013
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: Stichting Epilepsie Instellingen Nederland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Asystole
• Cardiac Arrhythmias
• Epilepsy

Intervention

Device:
• implantable heart rate monitor
Implantation of Reveal XT

Locations

Country	Name	City	State
Netherlands	Atrium Medical Center	Heerlen
Netherlands	Epilepsy center Kempenhaeghe	Heeze
Netherlands	Epilepsy Instititute in the Netherlands Foundation (SEIN)	Hoofddorp
Netherlands	Antonius Hospital	Sneek

Sponsors (3)

Lead Sponsor	Collaborator
Stichting Epilepsie Instellingen Nederland	Fonds NutsOhra, Medtronic

Country where clinical trial is conducted

Netherlands, 

References & Publications (5)

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. — View 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. — View 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. — View 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The percentage of seizure-related cardiac arrhythmias	The number of seizures during which a cardiac arrhythmia occurs divided by the total number of seizures during this study	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)	No
Other	The percentage of patients with a cardioinhibitory response to head-up tilt-testing	The number of patients with a cardioinhibitory response to head-up tilt-testing (1) heart rate rising initially then falling to a ventricular rate of <40 bpm for >10 seconds or asystole occurring for >3 seconds, with blood pressure rising initially then falling before the heart rate falls 2) Heart rate rising initially then falling to a ventricular rate <40 bpm for >10 seconds or asystole occurring for >3 seconds, with blood pressure rising initially and only falling to hypotensive levels <80 mm Hg systolic at or after the onset of rapid and severe heart rate fall) divided by the number of patients in whom tilt-testing was performed.	During one head-up tilt-test (approximate duration 1,5 hours)	No
Primary	Incidence and two-year prevalence of clinically relevant cardiac arrhythmia.	Clinical relevant cardiac arrhythmia is defined as: Asystole of = 6s together with clinical symptoms (lightheadedness, syncope, seizure) as indicated by seizure diary, activation of the portable seizure monitor, or patient activation of Reveal XT. The time frame between the reported clinical symptoms and the recorded event should not exceed 15 minutes.; Asystole of =10s regardless of report of clinical symptoms; Other cardiac arrhythmias of clinical significance: polymorphic sustained or non-sustained ventricular tachycardia (VT); non-sustained monomorphic VT of >180 bpm and >2s duration, or >175 bpm and >3s duration, and sustained monomorphic VT; atrial fibrillation (AF) of >200 bpm and >30s duration, or <55 bpm and clinical symptoms (dizziness or dyspnea); persistent sinus bradycardia of <40 bpm during physical activity; asymptomatic 2nd or 3rd degree atrioventricular (AV) block of >4s duration	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)	No
Secondary	the number of patients who will have received a permanent pacemaker at the end of this study.	Participants who will exhibit a clinically relevant arrhythmia (see our primary endpoints) during this study will be referred to an independent cardiologist for further evaluation and/or treatment. In a certain number of cases, this cardiologist will decide with the patient that pacemaker implantation would be the appropriate cause of action.	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)	No