An Arrhythmia Risk Stratification and Genetic Trial (EUTrigTreat)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University Medical Center Goettingen
Sponsor:
Collaborators:
UMC Utrecht
Katholieke Universiteit Leuven
University of Athens
Information provided by (Responsible Party):
Markus Zabel, University Medical Center Goettingen
ClinicalTrials.gov Identifier:
NCT01209494
First received: September 24, 2010
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The prospective EUTrigTreat multi-center study is an observational, advanced diagnostics and genetic risk stratification trial in patients with standard indications for ICD treatment, with and without myocardial infarction in their history.

Its aims are fourfold: 1) To accurately risk stratify a large cohort of implantable cardioverter-defibrillator (ICD) patients for ICD shock risk and mortality using traditional risk markers as well as genetic markers 2) To find a link between repolarization biomarkers and genetic markers of calcium metabolism. 3) To compare invasive and noninvasive electrophysiologic (EP) testing systematically 4) To assess temporal changes of typical noninvasive risk stratifiers and their prognostic implication.

In five European academic clinical centers, 700 ICD patients are prospectively enrolled (optionally the number of enrolled patients may be expanded to 1000 patients). Comprehensive non-invasive risk stratifying ECG diagnostics including beat-to-beat variability of repolarization (BVR) are applied, and candidate genes associated with malignant arrhythmias are analyzed. Programmed electrical stimulation is performed to test for inducibility of malignant ventricular arrhythmias and BVR. In a subset of patients, electrophysiologic studies include recording of monophasic action potentials (MAP) from the right ventricle for assessment of restitution properties. Non-invasive risk stratifying ECG methods are repeated annually. Outcome (mortality, ICD shocks) will be assessed until September 2014.


Condition
Cardiomyopathies, Primary
Arrhythmia
Sudden Cardiac Death
Calcium Metabolism Disorders

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The EU TrigTreat Clinical Study: An Advanced Diagnostics and Observational Trial for Arrhythmia Risk Stratification and Correlation With Genotype

Resource links provided by NLM:


Further study details as provided by University Medical Center Goettingen:

Primary Outcome Measures:
  • Total Mortality [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Sudden Cardiac, Cardiac and Non-Cardiac Mortality [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]
    The standard definition of SCD applied. A cardiac death is defined as any death presumed to have occurred from a cardiac cause other than SCD. Non-cardiac deaths are all other deaths.

  • Appropriate and Inappropriate Shocks [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]

    Appropriate shock is a secondary endpoint. ICD shock is classified as appropriate if delivered for a true ventricular tachyarrhythmia in the VT or VF zone. Appropriate ICD shock is classified as 1 primarily delivered in the VF zone, 2 secondarily delivered as a backup to failed ATP in the VT zone or 3 secondarily delivered after acceleration of failed ATP to VF zone.

    Inappropriate shock is a secondary endpoint. Inappropriate shock is an ICD shock caused by oversensing of cardiac or non-cardiac electrical signals as VT or VF, or by inappropriate interpretation of SVT as VT/VF by the device.


  • Secondary Composite Endpoints [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]
    A secondary composite endpoint of total mortality and appropriate ICD shocks is defined. Another secondary composite endpoint is defined as the sum of appropriate and inappropriate ICD shocks, i.e. all ICD shocks.


Biospecimen Retention:   Samples With DNA

Whole blood specimens for genetic analyses


Estimated Enrollment: 700
Study Start Date: January 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Invasive EP Study Group
200 patients are studied before clinically indicated (according to AHA/ACC/ESC guidelines) first ICD implantation or ICD exchange. Invasive EP study is performed to test inducibility of malignant arrhythmia. In addition MAP recordings are performed for measurements of restitution properties. Pacing is done for 12-lead ECG and MAP recordings for analysis of BVR and TWA, if applicable.
Noninvasive EP Study Group

The assignment of patients to the invasive and noninvasive EP groups does not occur by randomization or for intervention.

In the noninvasive EP study group, 500 patients with chronically implanted ICD (>3 month after implantation) are investigated using non-invasive EP study via ICD programmer. Programmed electrical stimulation is performed to test for inducibility of malignant arrhythmia. In addition pacing is done for measurements of BVR from the 12-lead ECG.


Detailed Description:

An increasing number of patients receive implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death. Within this group, it is difficult to differentiate between patients at high risk with need for additional treatment and, on the other hand, patients at low risk without benefit from implantable cardioverter-defibrillator therapy. Risk stratification techniques have been studied extensively over the last decades, but no conclusive recommendations can be found in the current guidelines for prevention of SCD. Furthermore, new genetic markers associated with sudden cardiac death were discovered recently, however, have not been implemented in concurrent risk analysis. Last, time dependent changes of risk stratification assessment are unknown.

The prospective EUTrigTreat multi-center study is an observational, advanced diagnostics and genetic risk stratification trial in patients with standard indications for ICD treatment and without myocardial infarction in their history.

Its aims are fourfold: 1) To accurately risk stratify a large cohort of implantable cardioverter-defibrillator (ICD) patients for ICD shock risk and mortality using traditional risk markers as well as genetic markers 2) To find a link between repolarization biomarkers and genetic markers of calcium metabolism. 3) To compare invasive and noninvasive electrophysiologic (EP) testing systematically 4) To assess temporal changes of typical noninvasive risk stratifiers and their prognostic implication.

In four European academic clinical centers, 700 ICD patients are prospectively enrolled. Optionally, the number of patients may be expanded to 1000. Comprehensive non-invasive risk stratifying ECG diagnostics including beat-to-beat variability of repolarization (BVR) are applied, and candidate genes associated with malignant arrhythmias are analyzed. Programmed electrical stimulation is performed to test for inducibility of malignant ventricular arrhythmias and BVR. In a subset of patients, electrophysiologic studies include recording of monophasic action potentials (MAP) from the right ventricle for assessment of restitution properties. Non-invasive risk stratifying ECG methods are repeated annually. Outcome (mortality, ICD shocks) will be assessed until September 2014.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with standard indications for ICD treatment according to ACC/AHA/ESC guidelines with and without myocardial infarction in their history are eligible for the study

Criteria

Inclusion Criteria:

  • Standard indication for ICD treatment according to ACC/AHA/ESC guidelines for primary or secondary prevention of SCD
  • Age ≥ 18 years
  • Nonischemic cardiomyopathies: DCM, HCM/HOCM, ARVC or
  • Channelopathies: Brugada, LQT, CPVT or
  • Idiopathic VT/VF or
  • Diffuse coronary artery disease, without transmural myocardial infarction in history (ACS and NSTEMI with CK maximum of 400 U/l allowed)

Exclusion Criteria:

  • Unstable cardiac disease
  • PCI or CABG < 3 months ago
  • Implantation of a CRT device < 6 months ago
  • ICD unable to deliver programmed ventricular stimulation via programmer (only in the noninvasive EP study group)
  • Women of childbearing potential in case of positive pregnancy test at the time of enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01209494

Contacts
Contact: Markus Zabel, M.D. +49 551 3910265 markus.zabel@med.uni-goettingen.de
Contact: Joachim Seegers, M.D. + 49 551 3910265 jseegers@med.uni-goettingen.de

Locations
Belgium
Katholieke Universiteit Leuven, Dept. of Cardiology Recruiting
Leuven, Belgium, 3000
Contact: Rik Willems, M.D., Ph.D.    +32 163 43397    rik.willems@med.kuleuven.be   
Contact: Hein Heidbüchel, M.D., Ph.D.    +32 163 43469    hein.heidbuchel@uz.kuleuven.ac.be   
Principal Investigator: Rik Willems, M.D., Ph.D.         
Sub-Investigator: Hein Heidbüchel, M.D., Ph.D.         
Sub-Investigator: Vincent Floré, M.D.         
Germany
University Medical Center Goettingen, Dept. of Cardiology and Pneumology Recruiting
Goettingen, Germany, 37075
Contact: Markus Zabel, M.D.    +49 551 3910265    markus.zabel@med.uni-goettingen.de   
Contact: Joachim Seegers, M.D.    +49 551 3910265    jseegers@med.uni-goettingen.de   
Principal Investigator: Markus Zabel, M.D.         
Sub-Investigator: Joachim Seegers, M.D.         
Sub-Investigator: Lars Lüthje, M.D.         
Sub-Investigator: Christian Sohns, M.D.         
Sub-Investigator: Pascal Muñoz Expósito, M.D.         
Sub-Investigator: Samuel T Sossalla, M.D.         
Greece
Attikon Hospital University of Athens, BRFAA, Dept. of Cardiology Recruiting
Athens, Greece, 17151
Contact: Panagotia Flevari, M.D.    +30 694 4942630    pflevari@yahoo.com   
Contact: Dimitrios T. Kremastinos, M.D.    +30 210 5832355    kremastinos@gmail.com   
Principal Investigator: Panagotia Flevari, M.D.         
Sub-Investigator: Dimitrios T Kremastinos, M.D.         
Netherlands
Universitair Medisch Centrum Utrecht, Depts. of Cardiology and Physiology Not yet recruiting
Utrecht, Netherlands, 3584 CM
Contact: Marc A. Vos, Ph.D.    +31 302 538900    m.a.vos@umcutrecht.nl   
Contact: Mathias Meine, M.D.    +31 887 555555    m.meine@umcutrecht.nl   
Principal Investigator: Marc A. Vos, Ph.D.         
Sub-Investigator: Mathias Meine, M.D.         
Sub-Investigator: Sofieke C Wijers, M.D.         
Sub-Investigator: Anton Tuinenburg, M.D.         
Sponsors and Collaborators
University Medical Center Goettingen
UMC Utrecht
Katholieke Universiteit Leuven
University of Athens
Investigators
Study Director: Markus Zabel, M.D. University Medical Center Goettingen
Principal Investigator: Marc A. Vos, Ph.D. UMC Utrecht
Principal Investigator: Panagotia Flevari, M.D. University of Athens
Principal Investigator: Rik Willems, M.D. Katholieke Universiteit Leuven
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Markus Zabel, Associate Professor, Head of Clinical Electrophysiology, University Medical Center Goettingen
ClinicalTrials.gov Identifier: NCT01209494     History of Changes
Other Study ID Numbers: HEALTH-F2-2009-241526
Study First Received: September 24, 2010
Last Updated: December 3, 2013
Health Authority: Germany: Ethics Commission
Greece: Ethics Committee
Belgium: Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Center Goettingen:
sudden cardiac death
implantable cardioverter defibrillator
ventricular arrhythmias
genetic syndromes
calcium metabolism
ventricular repolarization
ECG
T wave
programmed electrical stimulation
alternans
late potentials
risk stratification

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Calcium Metabolism Disorders
Death
Metabolic Diseases
Cardiomyopathies
Death, Sudden, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Heart Arrest
Death, Sudden

ClinicalTrials.gov processed this record on July 28, 2014