Cardiac Arrhythmias in Epilepsy: the CARELINK-study

NCT01946776 | Completed

• 1 other identifier: 1201-071
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 4

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).

Conditions

Epilepsy; Asystole; Cardiac Arrhythmias

Outcome Measures

Primary Outcomes (1)

• Incidence and two-year prevalence of clinically relevant cardiac arrhythmia.

  Clinical relevant cardiac arrhythmia is defined as: 1. 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. 2. Asystole of ≥10s regardless of report of clinical symptoms 3. Other cardiac arrhythmias of clinical significance: 1. polymorphic sustained or non-sustained ventricular tachycardia (VT) 2. non-sustained monomorphic VT of \>180 bpm and \>2s duration, or \>175 bpm and \>3s duration, and sustained monomorphic VT 3. atrial fibrillation (AF) of \>200 bpm and \>30s duration, or \<55 bpm and clinical symptoms (dizziness or dyspnea) 4. persistent sinus bradycardia of \<40 bpm during physical activity 5. 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)

Secondary Outcomes (1)

• the number of patients who will have received a permanent pacemaker at the end of 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)

Other Outcomes (2)

• The percentage of seizure-related cardiac arrhythmias

  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)

• The percentage of patients with a cardioinhibitory response to head-up tilt-testing

  During one head-up tilt-test (approximate duration 1,5 hours)

Study Arms (1)

Reveal XT

OTHER

People with drug-resistant epilepsy whose heart rhythm will be monitored continuously for 2 years using Reveal XT, an implantable heart rate monitor.

Device: implantable heart rate monitor

Interventions

implantable heart rate monitor DEVICE

Implantation of Reveal XT

Also known as: Reveal XT

Reveal XT

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stichting Epilepsie Instellingen Nederland: lead
• Fonds NutsOhra: collaborator
• Medtronic: collaborator

Study Sites (4)

Atrium Medical Center

Heerlen, Netherlands

Location

Epilepsy center Kempenhaeghe

Heeze, Netherlands

Location

Epilepsy Instititute in the Netherlands Foundation (SEIN)

Hoofddorp, 2130 AM, Netherlands

Location

Antonius Hospital

Sneek, Netherlands

Location

Related Publications (5)

• 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.

  PMID: 19668244 BACKGROUND

• 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.

  PMID: 17664402 BACKGROUND

• 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.

  PMID: 15610808 BACKGROUND

• 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.

  PMID: 22709423 BACKGROUND

• 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.

  PMID: 20067509 BACKGROUND

MeSH Terms

Conditions

Epilepsy; Heart Arrest; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Roland D Thijs, PhD

  SEIN-Epilepsy Institute in the Netherlands Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2013
• First Posted: September 20, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: December 26, 2016

Record last verified: 2016-12

Locations

NL (4)