PREDETERMINE Cohort Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
St. Jude Medical
Northwestern University
Information provided by (Responsible Party):
Christine M. Albert, MD, MPH, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01114269
First received: April 29, 2010
Last updated: July 17, 2014
Last verified: May 2014
  Purpose

This is a prospective, multi-center cohort study of patients with a history of coronary artery disease (CAD) and documentation of either a prior myocardial infarction (MI) or mild to moderate left ventricular dysfunction (LVEF 35-50%). The primary objective of this study is to identify a series of markers that alone or in combination specifically predict risk of arrhythmic death as compared to other causes of mortality among this at risk population of coronary heart disease (CHD) patients with preserved left ventricular ejection fraction (LVEF> 35%). In addition, we will also address whether these promising genetic markers and biomarkers advance sudden cardiac death (SCD) risk prediction when combined with advanced substrate imaging by participants that have undergone a contrast enhanced (CE) MRI at baseline.


Condition
Coronary Artery Disease
Left Ventricular Dysfunction
Sudden Cardiac Death

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • To identify a series of genetic markers and biomarkers that specifically predict risk of arrhythmic death as compared to other causes of mortality among CAD patients with preserved left ventricular ejection fraction (LVEF > 35%). [ Time Frame: Once an adequate number of sudden arrhythmic events (~n=400) has accrued a nested case-cohort design will be utilized to test for associations between biomarkers and sudden arrhythmic events. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine whether these genetic markers and biomarkers advance SCD risk prediction when combined with advanced substrate imaging by CE-MRI. [ Time Frame: Once an adequate number of sudden arrhythmic events (~n=400) has accrued a nested case-cohort design will be utilized to test for associations between genetic variants and sudden arrhythmic events. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

plasma, buffy coat, and red blood cells


Estimated Enrollment: 5800
Study Start Date: June 2007
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Detailed Description:

There are an estimated 250,000-400,000 sudden cardiac deaths (SCD) annually in the United States constituting approximately 50% of all cardiac deaths. Although clinical trials have demonstrated convincing survival benefits conferred by implantable cardioverter defibrillator (ICD) therapy in selected patients with left ventricular ejection fractions (LVEF) less than 35% and congestive heart failure, the overwhelming majority of patients who suffer a cardiac arrest will have an LVEF> 0.35. The PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study seeks to identify patients at a substantially higher risk of arrhythmic death among coronary heart disease (CHD) patients with preserved left ventricular ejection fractions (LVEF>35%). If biomarkers or genetic markers are identified that can specifically predict risk of ventricular arrhythmias, then these markers may serve as relatively inexpensive methods to identify those at risk. The public health impact of identifying markers could be quite substantial, leading to more efficient utilization of ICDs and advances in our understanding of mechanisms underlying SCD.

The PRE-DETERMINE Study is a prospective, multi-center study of patients with a history of coronary artery disease (CAD) and documentation of either a prior myocardial infarction (MI) or mild to moderate left ventricular dysfunction (LVEF 35-50%). Patients will be enrolled at about 100 sites where information on baseline demographic, clinical characteristics, pertinent past medical history, lifestyle habits, and medications will be collected. Electrocardiograms along with a blood sample will also be collected at baseline, sent to central laboratories, and stored for future analyses. The participants contact information will be collected and stored in a secure database and all participants will be followed centrally on a 6-month basis via mail/phone to document interim non-fatal arrhythmic events and cause-specific mortality. Study endpoints will be confirmed through review of medical records, interviews with next-of-kin, death certificates, and autopsy reports, if available.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Participants will be recruited throughout multicenter sites, which are participating in the PRE-DETERMINE Cohort Study. We plan to enroll patients with a history of coronary artery disease and documentation of either a prior myocardial infarction (MI) or mild to moderate left ventricular dysfunction (LVEF 35-50%). The clinical study staff at each site, which may be a research nurse, fellow, or physician will approach eligible patients to discuss their potential participation.

Criteria

Inclusion Criteria

  1. Evidence of Coronary Artery Disease (CAD) a or documented prior Myocardial Infarction.
  2. LVEF >35% by any current standard evaluation technique (e.g.,) echocardiogram, MUGA, angiography). 2.1. Patients who have an LVEF between 30-35% and NYHA Class I heart failure who do not have history of ventricular tachyarrhythmias,or inducible ventricular tachycardia during electrophysiological (EP) testing can be enrolled.
  3. If documented prior MI is not present, evidence of mild-moderate systolic Left Ventricular Dysfunction with an EF >35- ≤50% as measured by any current standard screening technique (e.g.,echocardiogram, MUGA, angiography) must be present.
  4. Patients aged 18 years or above

    1. CAD will be defined as evidence of one of the following two (2) criteria:

      • Significant stenosis of a major epicardial vessel (>50% proximal or 70% distal) by coronary angiography
      • Prior revascularization (percutaneous coronary intervention or coronary artery bypass surgery)
    2. MI can be documented in the following ways:

      • From the MI hospitalization: Detection of a rise and fall of cardiac biomarkers > 99th percentile of lab (e.g., CPK elevation or Troponin at least > two times the upper limit of normal) together with myocardial ischemia with at least one of the following:

        • Symptoms of Ischemia
        • ECG changes indicative of new ischemia (new ST-T changes or new LBBB)
        • Development of pathological Q waves
        • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
      • If no report from the MI hospitalization is available, prior MI can be met by either of the following:

        • Development of pathological Q waves
        • Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischaemic cause

Exclusion Criteria

  1. History of cardiac arrest or spontaneous or inducible sustained VT (15 beats or more at a rate of 120 BPM or greater - the occurrence of cardiac arrest or spontaneous VT in the setting of an acute MI is not considered an exclusion).
  2. Unexplained syncope
  3. Current or planned implantable cardiac defibrillator (ICD)
  4. Any condition other than cardiac disease that, in the investigator's judgment, would seriously limit life expectancy (poor survival)
  5. Metastatic cancer
  6. Marked valvular heart disease requiring surgical intervention
  7. Current or planned cardiac, renal or liver transplant
  8. Current alcohol or drug abuse
  9. Unwilling or unable to provide informed consent
  10. LVEF <35% with Class II-III CHF or LVEF <30%
  11. Participation in a clinical trial where the active treatment arm is testing an agent and/or intervention with known antiarrhythmic properties
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01114269

  Show 90 Study Locations
Sponsors and Collaborators
Brigham and Women's Hospital
St. Jude Medical
Northwestern University
Investigators
Principal Investigator: Christine M Albert, MD, MPH Brigham and Women's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Christine M. Albert, MD, MPH, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01114269     History of Changes
Other Study ID Numbers: 2007-P-000840, 3041108, R01HL091069
Study First Received: April 29, 2010
Last Updated: July 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Coronary Artery Disease
Sudden Cardiac Death
Myocardial Infarction
Percutaneous coronary intervention
Implantable Cardiac Defibrillator

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Death
Death, Sudden, Cardiac
Ventricular Dysfunction, Left
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Heart Arrest
Death, Sudden

ClinicalTrials.gov processed this record on July 31, 2014