DISCOVERY: Diagnostic Data and Genetic Polymorphisms in ICD Patients.

NCT00478933 | Completed Results

• 1 other identifier: DISCOVERY
• Study Type: interventional
• Target: 1,223
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Death, Sudden, Cardiac; Ventricular Fibrillation; Tachycardia; Atrial Fibrillation; Sick Sinus Syndrome

Keywords

Arrhythmia; Ventricular; Atrial; Tachycardia; Fibrillation; Flutter; GNB3; GNAS; GNAQ

Outcome Measures

Primary Outcomes (7)

• 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.

  2 years

• 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.

  2 years

• 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.

  2 years

• 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.

  2 years

• 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.

  2 years

• 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.

  2 years

• 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.

  2 years

Secondary Outcomes (2)

• Hospitalization, Medical Interventions, Medication, Surgery, Additional Diagnostics

  2 years

• All Cause Mortality, Cardiac Death and Atrial Fibrillation/Flutter

  2 years

Study Arms (1)

ICD Therapy, blood sampling

EXPERIMENTAL

Blood sampling Defibrillator, Dual Chamber ; Implantable

Device: Defibrillator, Dual Chamber ; Implantable; Procedure: Blood sampling

Interventions

Defibrillator, Dual Chamber ; Implantable DEVICE

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.

ICD Therapy, blood sampling

Blood sampling PROCEDURE

Blood sampling

ICD Therapy, blood sampling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 ).

Sponsors & Collaborators

• Medtronic Cardiac Rhythm and Heart Failure: lead

Related Publications (1)

• 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.

  PMID: 27895044 DERIVED

MeSH Terms

Conditions

Death, Sudden, Cardiac; Ventricular Fibrillation; Tachycardia; Atrial Fibrillation; Sick Sinus Syndrome; Arrhythmias, Cardiac

Interventions

Defibrillators; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiac Conduction System Disease; Arrhythmia, Sinus; Heart Block

Intervention Hierarchy (Ancestors)

Electrodes; Electrical Equipment and Supplies; Equipment and Supplies; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The following limitations can be noted: • Patient follow-up was prematurely terminated after at least 12-month follow-up data on all enrolled patients but before the planned 24-month follow-up.

Results Point of Contact

• Title: Margriet Kruijshoop, Clinical Research Manager
• Organization: Medtronic BRC

margriet.kruijshoop@medtronic.com

+31623910708

Study Officials

• Domenico Corrado, MD

  University of Padova, Italy

  PRINCIPAL INVESTIGATOR

• Heiner Wieneke, MD

  Universitätsklinikum Essen, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: patients and investigators were blinded to the genetic markers during the study. Therefore, no arm is specified as this is not applicable.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2007
• First Posted: May 25, 2007
• Study Start: February 1, 2007
• Primary Completion: July 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 2, 2025
• Results First Posted: November 22, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share