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PRE-DETERMINE Cohort Study

Active, not recruiting
Conditions
Left Ventricular Dysfunction
Coronary Artery Disease
Sudden Cardiac Death
Registration Number
NCT01114269
Lead Sponsor
Brigham and Women's Hospital
Brief Summary

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 determine whether biologic markers and ECGs can be utilized to advance SCD risk prediction in patients with CHD and LVEF\>30-35%. The overarching goal of the 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\> 30-35%). If biologic or ECG 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.

Detailed Description

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 were enrolled at 135 sites where information on baseline demographics, clinical characteristics, pertinent past medical history, lifestyle habits, cardiac test results, and medications were collected via electronic data capture. Electrocardiograms along with a blood sample was also collected at baseline, sent to central laboratories, and stored for future analyses. Contrast-enhanced magnetic resonance imaging (CE-MRI) scans were collected on a subset of patients and analyzed. Enrollment closed in November 2013 and patients are now being followed centrally by the Clinical Coordinating Center via mail/phone to document interim non-fatal arrhythmic events and cause-specific mortality. Questionnaires that inquire about intervening ICD implantations, ICD therapies, cardiac arrest, and other pertinent cardiovascular endpoints are mailed to participants every six months, and follow-up telephone calls are made to non-responders. Study endpoints are being confirmed through review of medical records, interviews with next-of-kin, and autopsy reports, if available.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
5764
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-IV 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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Sudden and/or arrhythmic cardiac death or resuscitated ventricular fibrillation.Median follow-up estimated to be 10.7 years

A definite sudden cardiac death (SCD) is defined as a death or fatal cardiac arrest occurring within 1 hour of symptom onset or the presence of autopsy consistent with SCD (e.g. acute coronary thrombosis). Probable SCD is defined as an unwitnessed death or death during sleep where the participant was observed to be symptom-free within the preceding 24 hours. Arrhythmic death is defined as the abrupt spontaneous collapse of circulation without antecedent circulatory or neurologic impairment. Deaths classified as non-arrhythmic are not included in the primary endpoint regardless of timing. Resuscitated ventricular fibrillation is defined as out-of-hospital cardiac arrests with documented VF and/or use of external electrical defibrillation for resuscitation.

Secondary Outcome Measures
NameTimeMethod
ICD ImplantationMedian follow-up estimated to be 10.7 years
Non-Sudden or Arrhythmic Causes of MortalityMedian follow-up estimated to be 10.7 years

Competing causes of mortality in competing risk analyses.

ICD ShockMedian follow-up estimated to be 10.7 years

ICD therapies for ventricular arrhythmias over 200 BPMs will be added to the endpoint.

Total Cardiac MortalityMedian follow-up estimated to be 10.7 years
Total MortalityMedian follow-up estimated to be 10.7 years

Trial Locations

Locations (90)

University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Colorado Heart and Vascular

🇺🇸

Denver, Colorado, United States

Wake Forest

🇺🇸

Winston-Salem, North Carolina, United States

Orlando Regional Medical Center

🇺🇸

Orlando, Florida, United States

Florida Hospital

🇺🇸

Orlando, Florida, United States

University of Michigan Medical Center

🇺🇸

Ann Arbor, Michigan, United States

The Cardiac Center of Creighton University

🇺🇸

Omaha, Nebraska, United States

Maimonides Medical Center

🇺🇸

Brooklyn, New York, United States

VA Medical Center - Charleston

🇺🇸

Charleston, South Carolina, United States

Cardiovascular Consultants

🇺🇸

Phoenix, Arizona, United States

University of Florida - Gainsville

🇺🇸

Gainesville, Florida, United States

Alaska Heart Institute

🇺🇸

Anchorage, Alaska, United States

Memorial Health System

🇺🇸

Colorado Springs, Colorado, United States

Phoenix Heart, PLLC

🇺🇸

Glendale, Arizona, United States

Beaver Medical Group/Clinical Care Research

🇺🇸

Banning, California, United States

Bay Area Cardiology Associates, P.A.

🇺🇸

Brandon, Florida, United States

Advocate Medical Group

🇺🇸

Chicago, Illinois, United States

Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

Georgia Heart Specialist

🇺🇸

Covington, Georgia, United States

Hawthorn Medical Associates

🇺🇸

North Dartmouth, Massachusetts, United States

Abington Memorial Hospital

🇺🇸

Abington, Pennsylvania, United States

Northeast Ohio Cardiovascular Specialists

🇺🇸

Akron, Ohio, United States

NECCR Internal Medicine and Cardiology Associates, LLC

🇺🇸

Fall River, Massachusetts, United States

New Mexico VA Healthcare Systems

🇺🇸

Albuquerque, New Mexico, United States

Community Heart and Vascular

🇺🇸

Anderson, Indiana, United States

Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Reliable Clinical Research

🇺🇸

Miami, Florida, United States

Oklahoma City VA Medical Center Veterans Research and Education Foundation

🇺🇸

Oklahoma City, Oklahoma, United States

Oklahoma Foundation for Cardiovascular Research

🇺🇸

Oklahoma City, Oklahoma, United States

Memphis VA Medical Center

🇺🇸

Memphis, Tennessee, United States

The University of Kansas

🇺🇸

Kansas City, Kansas, United States

McLaren Medical Center - Macomb

🇺🇸

Mount Clemens, Michigan, United States

Advanced Heartcare, LLC

🇺🇸

Bridgewater, New Jersey, United States

St. Joseph Regional Medical Center

🇺🇸

Paterson, New Jersey, United States

Providence Health Center

🇺🇸

Waco, Texas, United States

Gotham Cardiovascular

🇺🇸

New York, New York, United States

Columbia University Health Center

🇺🇸

New York, New York, United States

Tallahassee Research Institute, Inc.

🇺🇸

Tallahassee, Florida, United States

Cardiovascular Associates Virginia Beach

🇺🇸

Virginia Beach, Virginia, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Advocate Medical Group - Heart and Vascular of IL

🇺🇸

Chicago, Illinois, United States

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

Iowa Heart Center

🇺🇸

West Des Moines, Iowa, United States

Baystate Cardiology

🇺🇸

Springfield, Massachusetts, United States

Northstate Clinical Research

🇺🇸

Lenoir, North Carolina, United States

Northwest Ohio Cardiology Consultants/The Toledo Hospital

🇺🇸

Toledo, Ohio, United States

Northeast Georgia Heart Center, P.C.

🇺🇸

Gainesville, Georgia, United States

Maine Research Associates

🇺🇸

Auburn, Maine, United States

Primary Care Cardiology Research

🇺🇸

Ayer, Massachusetts, United States

Michigan Heart

🇺🇸

Ypsilanti, Michigan, United States

St. Elizabeth Medical Center - Hotvedt

🇺🇸

Utica, New York, United States

Minneapolis VA Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Cardiology Associates of Palm Beach - West Palm Beach

🇺🇸

West Palm Beach, Florida, United States

University of Missouri Health Care

🇺🇸

Columbia, Missouri, United States

Baptist Health Lexington

🇺🇸

Lexington, Kentucky, United States

Albany Associates Cardiology

🇺🇸

Albany, New York, United States

Velella Research

🇺🇸

Sarasota, Florida, United States

Glacier View Cardiology

🇺🇸

Kalispell, Montana, United States

Buffalo General Hospital/Kaleida Health

🇺🇸

Buffalo, New York, United States

Palm Beach Gardens Research Center

🇺🇸

Palm Beach Gardens, Florida, United States

Leonard J. Chabert Medical Center

🇺🇸

Houma, Louisiana, United States

Maine Research Associates - Lewiston

🇺🇸

Lewiston, Maine, United States

Transcatheter Medical, Inc. Centro Cardiovascular de Caguas y del Caribe

🇵🇷

Rio Piedras, Puerto Rico

St. Luke's Bethlehem

🇺🇸

Bethlehem, Pennsylvania, United States

Pinehurst Medical Clinic, Inc.

🇺🇸

Pinehurst, North Carolina, United States

Mississauga Clinical Research Centre

🇨🇦

Mississauga, Ontario, Canada

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

MetroHealth Medical Center

🇺🇸

Cleveland, Ohio, United States

Winthrop-University Hospital

🇺🇸

Mineola, New York, United States

Eastern Carolina Cardiovascular

🇺🇸

Elizabeth City, North Carolina, United States

Sanford Cardiology

🇺🇸

Sanford, North Carolina, United States

Cardiovasular Research of Knoxville

🇺🇸

Knoxville, Tennessee, United States

Asheville Cardiology Associates

🇺🇸

Asheville, North Carolina, United States

St. Luke's Episcopal Hospital

🇺🇸

Houston, Texas, United States

Vancouver General Hospital

🇨🇦

Vancouver, British Columbia, Canada

North Ohio Research, Ltd.

🇺🇸

Elyria, Ohio, United States

AnMed Health

🇺🇸

Anderson, South Carolina, United States

Non-Invasive Cardiovascular PA

🇺🇸

Houston, Texas, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Black Hills Cardiovascular Research

🇺🇸

Rapid City, South Dakota, United States

Intermountain Medical Center

🇺🇸

Murray, Utah, United States

Mercy Medical Associates

🇺🇸

Fairfield, Ohio, United States

Doylestown Cardiology Associates

🇺🇸

Doylestown, Pennsylvania, United States

Consultants in Cardiovascular Medicine

🇺🇸

Melrose Park, Illinois, United States

Jamaica Hospital Medical Center

🇺🇸

Jamaica, New York, United States

Oakwood Hospital & Medical Center

🇺🇸

Dearborn, Michigan, United States

Mid-Valley Cardiology

🇺🇸

Kingston, New York, United States

Carolina Cardiology Associates

🇺🇸

Rock Hill, South Carolina, United States

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