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DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients. (DISCOVERY)

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ClinicalTrials.gov Identifier: NCT00478933
Recruitment Status : Completed
First Posted : May 25, 2007
Results First Posted : November 22, 2017
Last Update Posted : November 22, 2017
Sponsor:
Information provided by (Responsible Party):
Medtronic Bakken Research Center

Brief Summary:

To prospectively evaluate if the analysis of genetic polymorphisms can be used to identify patients at risk of ventricular tachycardia.

To evaluate the influence of ICD-based diagnostic information on the long term treatment and management of primary prevention ICD-patients.


Condition or disease Intervention/treatment Phase
Death, Sudden, Cardiac Ventricular Fibrillation Tachycardia Atrial Fibrillation Sick Sinus Syndrome Device: Defibrillator, Dual Chamber ; Implantable Procedure: Blood sampling Not Applicable

Detailed Description:

Evaluate the positive predictive value of single nucleotide polymorphisms (SNPs) in the genes GNB3, GNAS and GNAQ as predictors of ventricular arrhythmia <400 msec.

  1. Evaluate the positive predictive value of Single Nucleotide Polymorphisms as predictor for death, cardiac death and atrial fibrillation/flutter in the genes GNB3, GNAS, GNAQ and other SNPs involving signal transduction components which impact on the activity of cardiac ion channels.
  2. Evaluate the best combination of genetic parameters, baseline data and follow-up data as predictor of primary endpoint, All cause Mortality, cardiac death and atrial arrhythmia.
  3. Evaluate the usage of ICD-system diagnostics (battery status, impedance, pacing threshold, sensing) resulting in medical consequences*.
  4. Evaluate the usage of ICD-based patient diagnostics (arrhythmia, IEGM, heart frequency, %pacing, Cardiac Compass) resulting in medical consequences*.
  5. Evaluate the frequency of programming changes involving AF-prevention and AF-therapy algorithms.
  6. Evaluate the frequency of pacing-parameter programming changes and the resulting medical consequences*.

    • Medical consequences include: Hospitalization, medical interventions, medication, surgery, additional diagnostics and ICD-programming changes.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1223 participants
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: patients and investigators were blinded to the genetic markers during the study. Therefore, no arm is specified as this is not applicable.
Primary Purpose: Diagnostic
Official Title: Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Tachy-arrhythmia in ICD Patients.
Study Start Date : February 2007
Actual Primary Completion Date : July 2012
Actual Study Completion Date : December 2012


Arm Intervention/treatment
Experimental: ICD Therapy, blood sampling
Blood sampling Defibrillator, Dual Chamber ; Implantable
Device: Defibrillator, Dual Chamber ; Implantable
Patient must wear a dual chamber ICD to remain in study. Can be enrolled 10 days prior to implant. Is excluded if device type changes.
Procedure: Blood sampling
Blood sampling



Primary Outcome Measures :
  1. Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype [ Time Frame: 2 years ]
    The GNAS c.393C>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.

  2. Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype [ Time Frame: 2 years ]
    The GNAS c.2273C>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.

  3. Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype [ Time Frame: 2 years ]
    The GNAS c.2291C>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.

  4. Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype [ Time Frame: 2 years ]
    The GNAQ c.-909/-908GC>TT single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.

  5. Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype [ Time Frame: 2 years ]
    The GNAQ c.-382G>A single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.

  6. Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype [ Time Frame: 2 years ]
    The GNAQ c.-387G>A single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.

  7. Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype [ Time Frame: 2 years ]
    The GNB3 c.825C>T single nucleotide polymorphism (SNP) was one of seven SNP's analyzed. Patients with de novo ICD implants were genotyped and followed for up to 2 years. All episodes of arrhythmia <400 msec. detected by the device were adjudicated by an independent committee. The number of patients with true arrhythmias <400 msec were tracked by genotype.


Secondary Outcome Measures :
  1. Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics [ Time Frame: 2 years ]
  2. All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter [ Time Frame: 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Implantation of a market approved Medtronic Dual-chamber ICD with long term clinical trends Cardiac Compass,
  • Subjects requiring the implantation of an ICD for primary prevention according to the current AHA/ACC/ESC guidelines,
  • Subject able to comply with the Clinical InvestigationPlan,
  • Subject is expected to remain available for follow-up visits,
  • Subject has signed the informed consent form within 10 days of implant,
  • The system implanted for this study is the first ICD implant for patient.

Exclusion Criteria:

  • Women who are pregnant, or women of childbearing potential not on a reliable form of birth control,
  • Subject is enrolled in a concurrent study that may confound the results of this study,
  • Subject has a life expectancy less than two years,
  • Subject is post heart transplant or awaiting heart transplantation,
  • Subject is anticipated to demonstrate poor compliance,
  • Subjects with syndromes known to be associated with ion channel pathologies such as:

    • Long- or short-QT Syndrome
    • Brugada Syndrome
    • Catecholaminergic Polymorphic Ventricular Tachycardia (CPTV ).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00478933


Sponsors and Collaborators
Medtronic Bakken Research Center
Investigators
Principal Investigator: Domenico Corrado, MD University of Padova, Italy
Principal Investigator: Heiner Wieneke, MD Universitätsklinikum Essen, Germany

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medtronic Bakken Research Center
ClinicalTrials.gov Identifier: NCT00478933     History of Changes
Other Study ID Numbers: DISCOVERY
First Posted: May 25, 2007    Key Record Dates
Results First Posted: November 22, 2017
Last Update Posted: November 22, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: study is closed several years ago; this is not applicable for this study

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medtronic Bakken Research Center:
Arrhythmia
Ventricular
Atrial
Tachycardia
Fibrillation
Flutter
GNB3
GNAS
GNAQ

Additional relevant MeSH terms:
Atrial Fibrillation
Tachycardia
Ventricular Fibrillation
Death, Sudden
Sick Sinus Syndrome
Death, Sudden, Cardiac
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Death
Arrhythmia, Sinus
Heart Block
Heart Arrest