PRE-DETERMINE Cohort Study

Coronary Artery Disease Clinical Trial

Official title:

PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01114269
• Other study ID #: 2007P000840
• Secondary ID: R01HL091069
• Status: Active, not recruiting
• Start date: July 2007
• Est. completion date: November 2026

Study information

• Verified date: March 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 5764
• Est. completion date: November 2026
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Death
• Death, Sudden, Cardiac
• Left Ventricular Dysfunction
• Myocardial Ischemia
• Sudden Cardiac Death
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Mississauga Clinical Research Centre	Mississauga	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Puerto Rico	Transcatheter Medical, Inc. Centro Cardiovascular de Caguas y del Caribe	Rio Piedras
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Northeast Ohio Cardiovascular Specialists	Akron	Ohio
United States	Albany Associates Cardiology	Albany	New York
United States	New Mexico VA Healthcare Systems	Albuquerque	New Mexico
United States	Alaska Heart Institute	Anchorage	Alaska
United States	AnMed Health	Anderson	South Carolina
United States	Community Heart and Vascular	Anderson	Indiana
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Asheville Cardiology Associates	Asheville	North Carolina
United States	Maine Research Associates	Auburn	Maine
United States	Primary Care Cardiology Research	Ayer	Massachusetts
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beaver Medical Group/Clinical Care Research	Banning	California
United States	St. Luke's Bethlehem	Bethlehem	Pennsylvania
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Bay Area Cardiology Associates, P.A.	Brandon	Florida
United States	Advanced Heartcare, LLC	Bridgewater	New Jersey
United States	Maimonides Medical Center	Brooklyn	New York
United States	Buffalo General Hospital/Kaleida Health	Buffalo	New York
United States	VA Medical Center - Charleston	Charleston	South Carolina
United States	Advocate Medical Group	Chicago	Illinois
United States	Advocate Medical Group - Heart and Vascular of IL	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Memorial Health System	Colorado Springs	Colorado
United States	University of Missouri Health Care	Columbia	Missouri
United States	Georgia Heart Specialist	Covington	Georgia
United States	Oakwood Hospital & Medical Center	Dearborn	Michigan
United States	Colorado Heart and Vascular	Denver	Colorado
United States	Doylestown Cardiology Associates	Doylestown	Pennsylvania
United States	Eastern Carolina Cardiovascular	Elizabeth City	North Carolina
United States	North Ohio Research, Ltd.	Elyria	Ohio
United States	Mercy Medical Associates	Fairfield	Ohio
United States	NECCR Internal Medicine and Cardiology Associates, LLC	Fall River	Massachusetts
United States	Northeast Georgia Heart Center, P.C.	Gainesville	Georgia
United States	University of Florida - Gainsville	Gainesville	Florida
United States	Phoenix Heart, PLLC	Glendale	Arizona
United States	Leonard J. Chabert Medical Center	Houma	Louisiana
United States	Non-Invasive Cardiovascular PA	Houston	Texas
United States	St. Luke's Episcopal Hospital	Houston	Texas
United States	Jamaica Hospital Medical Center	Jamaica	New York
United States	Glacier View Cardiology	Kalispell	Montana
United States	The University of Kansas	Kansas City	Kansas
United States	Mid-Valley Cardiology	Kingston	New York
United States	Cardiovasular Research of Knoxville	Knoxville	Tennessee
United States	Northstate Clinical Research	Lenoir	North Carolina
United States	Maine Research Associates - Lewiston	Lewiston	Maine
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Consultants in Cardiovascular Medicine	Melrose Park	Illinois
United States	Memphis VA Medical Center	Memphis	Tennessee
United States	Reliable Clinical Research	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Winthrop-University Hospital	Mineola	New York
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	McLaren Medical Center - Macomb	Mount Clemens	Michigan
United States	Intermountain Medical Center	Murray	Utah
United States	Columbia University Health Center	New York	New York
United States	Gotham Cardiovascular	New York	New York
United States	Hawthorn Medical Associates	North Dartmouth	Massachusetts
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	The Cardiac Center of Creighton University	Omaha	Nebraska
United States	Florida Hospital	Orlando	Florida
United States	Orlando Regional Medical Center	Orlando	Florida
United States	Palm Beach Gardens Research Center	Palm Beach Gardens	Florida
United States	St. Joseph Regional Medical Center	Paterson	New Jersey
United States	Cardiovascular Consultants	Phoenix	Arizona
United States	Pinehurst Medical Clinic, Inc.	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Black Hills Cardiovascular Research	Rapid City	South Dakota
United States	Carolina Cardiology Associates	Rock Hill	South Carolina
United States	Sanford Cardiology	Sanford	North Carolina
United States	Velella Research	Sarasota	Florida
United States	Baystate Cardiology	Springfield	Massachusetts
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Tallahassee Research Institute, Inc.	Tallahassee	Florida
United States	Northwest Ohio Cardiology Consultants/The Toledo Hospital	Toledo	Ohio
United States	St. Elizabeth Medical Center - Hotvedt	Utica	New York
United States	Cardiovascular Associates Virginia Beach	Virginia Beach	Virginia
United States	Providence Health Center	Waco	Texas
United States	Iowa Heart Center	West Des Moines	Iowa
United States	Cardiology Associates of Palm Beach - West Palm Beach	West Palm Beach	Florida
United States	Wake Forest	Winston-Salem	North Carolina
United States	Michigan Heart	Ypsilanti	Michigan

Sponsors (6)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Abbott Medical Devices, National Heart, Lung, and Blood Institute (NHLBI), Northwestern University, Quintiles, Inc., Roche Diagnostics

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (6)

Chatterjee NA, Moorthy MV, Pester J, Schaecter A, Panicker GK, Narula D, Lee DC, Goldberger JJ, Kadish A, Cook NR, Albert CM; PRE-DETERMINE Study Group. Sudden Death in Patients With Coronary Heart Disease Without Severe Systolic Dysfunction. JAMA Cardiol — View Citation

Chatterjee NA, Tikkanen JT, Panicker GK, Narula D, Lee DC, Kentta T, Junttila JM, Cook NR, Kadish A, Goldberger JJ, Huikuri HV, Albert CM; PREDETERMINE Investigators. Simple electrocardiographic measures improve sudden arrhythmic death prediction in coron — View Citation

Lee DC, Albert CM, Narula D, Kadish AH, Panicker GK, Wu E, Schaechter A, Pester J, Chatterjee NA, Cook NR, Goldberger JJ. Estimating Myocardial Infarction Size With a Simple Electrocardiographic Marker Score. J Am Heart Assoc. 2020 Feb 4;9(3):e014205. doi — View Citation

Panicker GK, Narula DD, Albert CM, Lee DC, Kothari S, Goldberger JJ, Cook N, Schaechter A, Kim E, Moorthy MV, Pester J, Chatterjee NA, Kadish AH, Karnad DR. Validation of electrocardiographic criteria for identifying left ventricular dysfunction in patien — View Citation

Silverman MG, Yeri A, Moorthy MV, Camacho Garcia F, Chatterjee NA, Glinge CSA, Tfelt-Hansen J, Salvador AM, Pico AR, Shah R, Albert CM, Das S. Circulating miRNAs and Risk of Sudden Death in Patients With Coronary Heart Disease. JACC Clin Electrophysiol. 2 — View Citation

Venkateswaran RV, Moorthy MV, Chatterjee NA, Pester J, Kadish AH, Lee DC, Cook NR, Albert CM. Diabetes and Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction. JACC Clin Electrophysiol. 2021 Dec;7(12):1604-1614. do — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sudden and/or arrhythmic cardiac death or resuscitated ventricular fibrillation.	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.	Median follow-up estimated to be 10.7 years
Secondary	ICD Shock	ICD therapies for ventricular arrhythmias over 200 BPMs will be added to the endpoint.	Median follow-up estimated to be 10.7 years
Secondary	ICD Implantation		Median follow-up estimated to be 10.7 years
Secondary	Total Cardiac Mortality		Median follow-up estimated to be 10.7 years
Secondary	Total Mortality		Median follow-up estimated to be 10.7 years
Secondary	Non-Sudden or Arrhythmic Causes of Mortality	Competing causes of mortality in competing risk analyses.	Median follow-up estimated to be 10.7 years

External Links

•   Cardiac Arrest
•   Coronary Artery Disease
•   Heart Disease
•   Pacemakers and Implantable Defibrillators
•   U.S. FDA Resources