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Cardiac Arrhythmias in Epilepsy: the CARELINK-study (CARELINK)

Primary Purpose

Epilepsy, Asystole, Cardiac Arrhythmias

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
implantable heart rate monitor
Sponsored by
Stichting Epilepsie Instellingen Nederland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Epilepsy

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Atrium Medical Center
  • Epilepsy center Kempenhaeghe
  • Epilepsy Instititute in the Netherlands Foundation (SEIN)
  • Antonius Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Reveal XT

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
August 29, 2013
Last Updated
December 23, 2016
Sponsor
Stichting Epilepsie Instellingen Nederland
Collaborators
Fonds NutsOhra, Medtronic
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1. Study Identification

Unique Protocol Identification Number
NCT01946776
Brief Title
Cardiac Arrhythmias in Epilepsy: the CARELINK-study
Acronym
CARELINK
Official Title
Cardiac Arrhythmias in Refractory Epilepsy: Identifying Prevalence and LINKage Between Seizures and Arrhythmias
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stichting Epilepsie Instellingen Nederland
Collaborators
Fonds NutsOhra, Medtronic

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Asystole, Cardiac Arrhythmias

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Reveal XT
Arm Type
Other
Arm Description
People with drug-resistant epilepsy whose heart rhythm will be monitored continuously for 2 years using Reveal XT, an implantable heart rate monitor.
Intervention Type
Device
Intervention Name(s)
implantable heart rate monitor
Other Intervention Name(s)
Reveal XT
Intervention Description
Implantation of Reveal XT
Primary Outcome Measure Information:
Title
Incidence and two-year prevalence of clinically relevant cardiac arrhythmia.
Description
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
Time Frame
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 Outcome Measure Information:
Title
the number of patients who will have received a permanent pacemaker at the end of this study.
Description
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.
Time Frame
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 Pre-specified Outcome Measures:
Title
The percentage of seizure-related cardiac arrhythmias
Description
The number of seizures during which a cardiac arrhythmia occurs divided by the total number of seizures during this study
Time Frame
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)
Title
The percentage of patients with a cardioinhibitory response to head-up tilt-testing
Description
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.
Time Frame
During one head-up tilt-test (approximate duration 1,5 hours)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roland D Thijs, PhD
Organizational Affiliation
SEIN-Epilepsy Institute in the Netherlands Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Atrium Medical Center
City
Heerlen
Country
Netherlands
Facility Name
Epilepsy center Kempenhaeghe
City
Heeze
Country
Netherlands
Facility Name
Epilepsy Instititute in the Netherlands Foundation (SEIN)
City
Hoofddorp
ZIP/Postal Code
2130 AM
Country
Netherlands
Facility Name
Antonius Hospital
City
Sneek
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
19668244
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.
Results Reference
background
PubMed Identifier
17664402
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.
Results Reference
background
PubMed Identifier
15610808
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.
Results Reference
background
PubMed Identifier
22709423
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.
Results Reference
background
PubMed Identifier
20067509
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.
Results Reference
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Cardiac Arrhythmias in Epilepsy: the CARELINK-study

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