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

Primary Purpose

Death, Sudden, Cardiac, Ventricular Fibrillation, Tachycardia

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Defibrillator, Dual Chamber ; Implantable
Blood sampling
Sponsored by
Medtronic Bakken Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Death, Sudden, Cardiac focused on measuring Arrhythmia, Ventricular, Atrial, Tachycardia, Fibrillation, Flutter, GNB3, GNAS, GNAQ

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 ).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    ICD Therapy, blood sampling

    Arm Description

    Blood sampling Defibrillator, Dual Chamber ; Implantable

    Outcomes

    Primary Outcome Measures

    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype
    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.
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype
    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.
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype
    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.
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype
    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.
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype
    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.
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype
    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.
    Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype
    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

    Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics
    All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter

    Full Information

    First Posted
    May 23, 2007
    Last Updated
    July 4, 2017
    Sponsor
    Medtronic Bakken Research Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00478933
    Brief Title
    DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients.
    Acronym
    DISCOVERY
    Official Title
    Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Tachy-arrhythmia in ICD Patients.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    February 2007 (undefined)
    Primary Completion Date
    July 2012 (Actual)
    Study Completion Date
    December 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Medtronic Bakken Research Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.
    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. 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. 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. Evaluate the usage of ICD-system diagnostics (battery status, impedance, pacing threshold, sensing) resulting in medical consequences*. Evaluate the usage of ICD-based patient diagnostics (arrhythmia, IEGM, heart frequency, %pacing, Cardiac Compass) resulting in medical consequences*. Evaluate the frequency of programming changes involving AF-prevention and AF-therapy algorithms. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Death, Sudden, Cardiac, Ventricular Fibrillation, Tachycardia, Atrial Fibrillation, Sick Sinus Syndrome
    Keywords
    Arrhythmia, Ventricular, Atrial, Tachycardia, Fibrillation, Flutter, GNB3, GNAS, GNAQ

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Masking Description
    patients and investigators were blinded to the genetic markers during the study. Therefore, no arm is specified as this is not applicable.
    Allocation
    N/A
    Enrollment
    1223 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    ICD Therapy, blood sampling
    Arm Type
    Experimental
    Arm Description
    Blood sampling Defibrillator, Dual Chamber ; Implantable
    Intervention Type
    Device
    Intervention Name(s)
    Defibrillator, Dual Chamber ; Implantable
    Intervention Description
    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.
    Intervention Type
    Procedure
    Intervention Name(s)
    Blood sampling
    Intervention Description
    Blood sampling
    Primary Outcome Measure Information:
    Title
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.393C>T Genotype
    Description
    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.
    Time Frame
    2 years
    Title
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2273C>T Genotype
    Description
    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.
    Time Frame
    2 years
    Title
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAS c.2291C>T Genotype
    Description
    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.
    Time Frame
    2 years
    Title
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-909/-908GC>TT Genotype
    Description
    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.
    Time Frame
    2 years
    Title
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-382G>A Genotype
    Description
    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.
    Time Frame
    2 years
    Title
    Number of Patients With Ventricular Arrhythmia <400 Msec. by GNAQ c.-387G>A Genotype
    Description
    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.
    Time Frame
    2 years
    Title
    Outcome Measure Title: Number of Patients With Ventricular Arrhythmia <400 Msec. by GNB3 c.825C>T Genotype
    Description
    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.
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics
    Time Frame
    2 years
    Title
    All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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 ).
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Domenico Corrado, MD
    Organizational Affiliation
    University of Padova, Italy
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Heiner Wieneke, MD
    Organizational Affiliation
    Universitätsklinikum Essen, Germany
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    study is closed several years ago; this is not applicable for this study
    Citations:
    PubMed Identifier
    27895044
    Citation
    Wieneke H, Svendsen JH, Lande J, Spencker S, Martinez JG, Strohmer B, Toivonen L, Le Marec H, Garcia-Fernandez FJ, Corrado D, Huertas-Vazquez A, Uy-Evanado A, Rusinaru C, Reinier K, Foldesi C, Hulak W, Chugh SS, Siffert W. Polymorphisms in the GNAS Gene as Predictors of Ventricular Tachyarrhythmias and Sudden Cardiac Death: Results From the DISCOVERY Trial and Oregon Sudden Unexpected Death Study. J Am Heart Assoc. 2016 Nov 28;5(12):e003905. doi: 10.1161/JAHA.116.003905.
    Results Reference
    derived

    Learn more about this trial

    DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients.

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