Clinical trial NCT01209494: An Arrhythmia Risk Stratification and Genetic Trial
Official title: The EU TrigTreat Clinical Study: An Advanced Diagnostics and Observational Trial for Arrhythmia Risk Stratification and Correlation With Genotype
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiomyopathies, Primary
Arrhythmia
Sudden Cardiac Death
Calcium Metabolism Disorders
Keywords: 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
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: KU Leuven
name: University of Athens
First posted: 2010-09-27
Enrollment: 672
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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 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

Primary outcomes:
measure: Total Mortality
timeFrame: 2010-2014
Secondary outcomes:
measure: Sudden Cardiac, Cardiac and Non-Cardiac Mortality
timeFrame: 2010-2014
measure: Appropriate and Inappropriate Shocks
timeFrame: 2010-2014
measure: Secondary Composite Endpoints
timeFrame: 2010-2014
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Katholieke Universiteit Leuven, Dept. of Cardiology
city: Goettingen
country: Germany
facility: University Medical Center Goettingen, Dept. of Cardiology and Pneumology
city: Athens
country: Greece
facility: Attikon Hospital University of Athens, BRFAA, Dept. of Cardiology
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht, Depts. of Cardiology and Physiology
Study officials:
affiliation: University Medical Center Goettingen
name: Markus Zabel, M.D.
role: STUDY_DIRECTOR
affiliation: UMC Utrecht
name: Marc A. Vos, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Athens
name: Panagotia Flevari, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven
name: Rik Willems, M.D.
role: PRINCIPAL_INVESTIGATOR
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