Cardiac Arrhythmias in Epilepsy: the CARELINK-study

This study is currently recruiting participants.
Verified August 2013 by Stichting Epilepsie Instellingen Nederland
Sponsor:
Collaborators:
Fonds NutsOhra
Medtronic
Information provided by (Responsible Party):
Stichting Epilepsie Instellingen Nederland
ClinicalTrials.gov Identifier:
NCT01946776
First received: August 29, 2013
Last updated: September 16, 2013
Last verified: August 2013
  Purpose

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).


Condition Intervention
Epilepsy
Asystole
Cardiac Arrhythmias
Device: implantable heart rate monitor

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Cardiac Arrhythmias in Refractory Epilepsy: Identifying Prevalence and LINKage Between Seizures and Arrhythmias

Resource links provided by NLM:


Further study details as provided by Stichting Epilepsie Instellingen Nederland:

Primary Outcome Measures:
  • Incidence and two-year prevalence of clinically relevant cardiac arrhythmia. [ 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) ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • the number of patients who will have received a permanent pacemaker at the end of 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) ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • The percentage of seizure-related cardiac arrhythmias [ 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) ] [ Designated as safety issue: No ]
    The number of seizures during which a cardiac arrhythmia occurs divided by the total number of seizures during this study

  • The percentage of patients with a cardioinhibitory response to head-up tilt-testing [ Time Frame: During one head-up tilt-test (approximate duration 1,5 hours) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Reveal XT
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
Other Name: Reveal XT

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01946776

Contacts
Contact: Roland D Thijs, MD PhD 0031-(0)235588948 rthijs@sein.nl

Locations
Netherlands
Atrium Medical Center Active, not recruiting
Heerlen, Netherlands
Epilepsy center Kempenhaeghe Recruiting
Heeze, Netherlands
Principal Investigator: Johan B Arends, MD PhD         
Epilepsy Instititute in the Netherlands Foundation (SEIN) Recruiting
Hoofddorp, Netherlands, 2130 AM
Principal Investigator: Roland D Thijs, MD PhD         
Antonius Hospital Active, not recruiting
Sneek, Netherlands
Sponsors and Collaborators
Stichting Epilepsie Instellingen Nederland
Fonds NutsOhra
Medtronic
Investigators
Principal Investigator: Roland D Thijs, PhD SEIN-Epilepsy Institute in the Netherlands Foundation
  More Information

Publications:
Responsible Party: Stichting Epilepsie Instellingen Nederland
ClinicalTrials.gov Identifier: NCT01946776     History of Changes
Other Study ID Numbers: 1201-071
Study First Received: August 29, 2013
Last Updated: September 16, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Epilepsy
Heart Arrest
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on April 17, 2014