Sudden Cardiac DeathGRADENCT02045043
Genetic Risk Assessment of Defibrillator Events
An observational study of Sudden Cardiac Death and Arrhythmias, run by University of Iowa at 6 sites in United States.
Trial summary
Arrhythmias remain a major health problem, causing at least 250,000 deaths annually in the United States. Pharmacological treatments often do more harm than good, and device therapies are limited by high cost and effects on quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sudden Cardiac Death, Arrhythmias, Congestive Heart Failure
- How many people
- 1,807 participants
- Where
- 6 sitesUnited States
- Study dates
- Mar 2002to Jun 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects 18 years of age and over with a cardiomyopathy, an ejection fraction less than or equal to 30%, and an implantable cardioverter defibrillator
Who may be able to join
- An ICD placed during the last 5 years, or a planned ICD within 1 month
- Age 18 or older
- Left Ventricular Ejection fraction < or = 30%
- Ability to give informed consent
Who cannot join
- Patient refuses or is unable to give consent
- A life expectancy <6 months from a non-cardiac life threatening disease
- Ongoing Class IV heart failure symptoms despite treatment
- History of cardiac transplant or left ventricular assist device
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Emory University
Atlanta, Georgia, 30322
Massuchetts General Hospital
Boston, Massachusetts, 02114
The Ohio State University
Columbus, Ohio, 43210
Mid Ohio Cardiology
Columbus, Ohio, 43214
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, 15240
About this study
Official title: Genetic Risk Assessment of Defibrillator Events: A Prospective Multicenter Observational Study
Arrhythmias remain a major health problem, causing at least 250,000 deaths annually in the United States. Pharmacological treatments often do more harm than good, and device therapies are limited by high cost and effects on quality of life. Ion channel mutations cause rare inherited arrhythmopathies, but account for only a small fraction of patients with life- threatening arrhythmias and sudden death. Most arrhythmias occur during myocardial ischemia, following myocardial infarction, and in patients with poor left ventricular (LV) function of any etiology. Aside from ejection fraction (EF), few clinically useful indicators to stratify the risk of sudden death have been identified. The role of subtle difference in ion channel expression and/or structure in predisposing patients to arrhythmias and modulating the risk of sudden death is unknown.
In this study, we are prospectively testing whether polymorphisms in ion channels and ion channel modifying genes are associated with arrhythmias in a population with internal cardioverter-defibrillators (ICDs) and poor LV function. We will test the hypothesis that functional polymorphisms in the coding sequences and promoter regions of cardiac genes (e.g. ion channels, beta-adrenergic receptors) predispose individuals to arrhythmias and /or heart failure progression.
We hope to identify genetic predictors for the common forms of sudden cardiac death. This would allow the identification of a subpopulation of heart failure patients that would benefit most from ICD placement.
- Keywords
- Sudden Cardiac Death, Arrhythmias, Congestive Heart Failure, Cardiomyopathy, Single Nucleotide Polymorphisms, Genomics
- Medical subject headings
- Death, Sudden, Cardiac, Arrhythmias, Cardiac, Heart Failure, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cardiomyopathy patients with ICDs | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Shock-Free Survival
Time to first appropriate shock from an Implantable Cardioverter-Defibrillator
Measured: Up to 5 years
Secondary outcomes (3)
Survival
Time to death from any cause
Measured: Up to 5 years
Transplant- and VAD-Free Survival
Time to occurence of death from any cause, cardiac transplantation, or Ventricular Assist Device placement (whichever comes first)
Measured: Up to 5 years
Appropriate Shock Frequency
The number of appropriate shocks per year
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2014 (estimated)
- Study startMar 2002
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Sudden Cardiac DeathStudies of the same condition, open and under way.
- More trials run by University of IowaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,807 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Barry London, University of Iowa
- Investigators
- Barry London, MD PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02045043
- Sponsor's protocol ID
- GRADE
- Other IDs
- R01HL077398
- Acronym
- GRADE
- Status last verified
- Jan 2014
- First submitted
- 22 Jan 2014
- Last updated
- 24 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, MacRae CA, Dudley SC, Shalaby AA, Weiss R, McNamara DM, London B, Ellinor PT. Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm. 2012 Mar;9(3):390-6. doi: 10.1016/j.hrthm.2011.10.016. Epub 2011 Oct 17.
PubMed 22004663Blanco RR, Austin H, Vest RN 3rd, Valadri R, Li W, Lassegue B, Song Q, London B, Dudley SC, Bloom HL, Searles CD, Zafari AM. Angiotensin receptor type 1 single nucleotide polymorphism 1166A/C is associated with malignant arrhythmias and altered circulating miR-155 levels in patients with chronic heart failure. J Card Fail. 2012 Sep;18(9):717-23. doi: 10.1016/j.cardfail.2012.06.531. Epub 2012 Aug 9.
PubMed 22939041Bloom HL, Shukrullah I, Veledar E, Gutmann R, London B, Dudley SC. Statins Decrease Oxidative Stress and ICD Therapies. Cardiol Res Pract. 2010;2010:253803. doi: 10.4061/2010/253803. Epub 2010 Mar 25.
PubMed 20369058Aleong RG, Mulvahill MJ, Halder I, Carlson NE, Singh M, Bloom HL, Dudley SC, Ellinor PT, Shalaby A, Weiss R, Gutmann R, Sauer WH, Narayanan K, Chugh SS, Saba S, London B. Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function. J Am Heart Assoc. 2015 Jul 31;4(8):e001566. doi: 10.1161/JAHA.114.001566.
PubMed 26231842AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; Genetic Risk Assessment of Defibrillator Events Investigators. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study). Am J Cardiol. 2015 Apr 1;115(7):924-31. doi: 10.1016/j.amjcard.2015.01.020. Epub 2015 Jan 15.
PubMed 25682436
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Risk Assessment of Defibrillator Events: A Prospective Multicenter Observational Study
- ClinicalTrials.gov ID
- NCT02045043
- Acronym / sponsor ID
- GRADE / GRADE
- Keywords
- Sudden Cardiac Death, Arrhythmias, Congestive Heart Failure, Cardiomyopathy, Single Nucleotide Polymorphisms, Genomics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,807 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2002
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 24 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Arrhythmias remain a major health problem, causing at least 250,000 deaths annually in the United States. Pharmacological treatments often do more harm than good, and device therapies are limited by high cost and effects on quality of life. Ion channel mutations cause rare inherited arrhythmopathies, but account for only a small fraction of patients with life- threatening arrhythmias and sudden death. Most arrhythmias occur during myocardial ischemia, following myocardial infarction, and in patients with poor left ventricular (LV) function of any etiology. Aside from ejection fraction (EF), few clinically useful indicators to stratify the risk of sudden death have been identified. The role of subtle difference in ion channel expression and/or structure in predisposing patients to arrhythmias and modulating the risk of sudden death is unknown.
In this study, we are prospectively testing whether polymorphisms in ion channels and ion channel modifying genes are associated with arrhythmias in a population with internal cardioverter-defibrillators (ICDs) and poor LV function. We will test the hypothesis that functional polymorphisms in the coding sequences and promoter regions of cardiac genes (e.g. ion channels, beta-adrenergic receptors) predispose individuals to arrhythmias and /or heart failure progression.
We hope to identify genetic predictors for the common forms of sudden cardiac death. This would allow the identification of a subpopulation of heart failure patients that would benefit most from ICD placement.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cardiomyopathy patients with ICDs | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects 18 years of age and over with a cardiomyopathy, an ejection fraction less than or equal to 30%, and an implantable cardioverter defibrillator
Key inclusion criteria (4 listed)
- An ICD placed during the last 5 years, or a planned ICD within 1 month
- Age 18 or older
- Left Ventricular Ejection fraction < or = 30%
- Ability to give informed consent
Key exclusion criteria (4 listed)
- Patient refuses or is unable to give consent
- A life expectancy <6 months from a non-cardiac life threatening disease
- Ongoing Class IV heart failure symptoms despite treatment
- History of cardiac transplant or left ventricular assist device
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Shock-Free Survival
Time frame: Up to 5 years
Time to first appropriate shock from an Implantable Cardioverter-Defibrillator
3 secondary outcomes
Survival
Time frame: Up to 5 years
Transplant- and VAD-Free Survival
Time frame: Up to 5 years
Appropriate Shock Frequency
Time frame: Up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2014.
- Background: PubMed 22004663Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, MacRae CA, Dudley SC, Shalaby AA, Weiss R, McNamara DM, London B, Ellinor PT. Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm. 2012 Mar;9(3):390-6. doi: 10.1016/j.hrthm.2011.10.016. Epub 2011 Oct 17.
- Results publication: PubMed 22939041Blanco RR, Austin H, Vest RN 3rd, Valadri R, Li W, Lassegue B, Song Q, London B, Dudley SC, Bloom HL, Searles CD, Zafari AM. Angiotensin receptor type 1 single nucleotide polymorphism 1166A/C is associated with malignant arrhythmias and altered circulating miR-155 levels in patients with chronic heart failure. J Card Fail. 2012 Sep;18(9):717-23. doi: 10.1016/j.cardfail.2012.06.531. Epub 2012 Aug 9.
- Results publication: PubMed 20369058Bloom HL, Shukrullah I, Veledar E, Gutmann R, London B, Dudley SC. Statins Decrease Oxidative Stress and ICD Therapies. Cardiol Res Pract. 2010;2010:253803. doi: 10.4061/2010/253803. Epub 2010 Mar 25.
- Derived from this study: PubMed 26231842Aleong RG, Mulvahill MJ, Halder I, Carlson NE, Singh M, Bloom HL, Dudley SC, Ellinor PT, Shalaby A, Weiss R, Gutmann R, Sauer WH, Narayanan K, Chugh SS, Saba S, London B. Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function. J Am Heart Assoc. 2015 Jul 31;4(8):e001566. doi: 10.1161/JAHA.114.001566.
- Derived from this study: PubMed 25682436AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; Genetic Risk Assessment of Defibrillator Events Investigators. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study). Am J Cardiol. 2015 Apr 1;115(7):924-31. doi: 10.1016/j.amjcard.2015.01.020. Epub 2015 Jan 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barry London, MD PhD principal investigator
University of Iowa
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sudden Cardiac Death and Arrhythmias, run by University of Iowa at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Shock-Free Survival (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02045043, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2014.