An Arrhythmia Risk Stratification and Genetic Trial (EUTrigTreat)

December 1, 2015 updated by: Markus Zabel, University Medical Center Goettingen

The EU TrigTreat Clinical Study: An Advanced Diagnostics and Observational Trial for Arrhythmia Risk Stratification and Correlation With Genotype

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

672

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Katholieke Universiteit Leuven, Dept. of Cardiology
  • Germany
      • Goettingen, Germany, 37075
        • University Medical Center Goettingen, Dept. of Cardiology and Pneumology
  • Greece
      • Athens, Greece, 17151
        • Attikon Hospital University of Athens, BRFAA, Dept. of Cardiology
  • Netherlands
      • Utrecht, Netherlands, 3584 CM
        • Universitair Medisch Centrum Utrecht, Depts. of Cardiology and Physiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Total Mortality
Time Frame: 2010-2014
2010-2014

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sudden Cardiac, Cardiac and Non-Cardiac Mortality
Time Frame: 2010-2014
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.
2010-2014
Appropriate and Inappropriate Shocks
Time Frame: 2010-2014

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.
2010-2014
Secondary Composite Endpoints
Time Frame: 2010-2014
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.
2010-2014

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Goettingen

Collaborators

KU Leuven
UMC Utrecht
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., KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

September 24, 2010

First Submitted That Met QC Criteria

September 24, 2010

First Posted (Estimate)

September 27, 2010

Study Record Updates

Last Update Posted (Estimate)

December 2, 2015

Last Update Submitted That Met QC Criteria

December 1, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HEALTH-F2-2009-241526

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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