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
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
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
NCT ID
NCT00478933
First Posted
May 23, 2007
Last Updated
July 4, 2017
Sponsor
Medtronic Bakken Research Center
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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