PRE-DETERMINE Cohort Study

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01114269

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), Abbott Medical Devices (Industry), Northwestern University (Other), Roche Diagnostics (Industry), Quintiles, Inc. (Industry)

5,764

Enrollment

Locations

183

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Left Ventricular Dysfunction Sudden Cardiac Death

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.

Study Design

Study Type:

Observational

Actual Enrollment :

5764 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

Study Start Date :

Jul 1, 2007

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Outcome Measures

Primary Outcome Measures

Sudden and/or arrhythmic cardiac death or resuscitated ventricular fibrillation. [Median follow-up estimated to be 8 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

ICD Shock [Median follow-up estimated to be 8 years]
ICD therapies for ventricular arrhythmias over 200 BPMs will be added to the endpoint.
ICD Implantation [Median follow-up estimated to be 8 years]
Total Cardiac Mortality [Median follow-up estimated to be 8 years]
Total Mortality [Median follow-up estimated to be 8 years]
Non-Sudden or Arrhythmic Causes of Mortality [Median follow-up estimated to be 8 years]
Competing causes of mortality in competing risk analyses.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Evidence of Coronary Artery Disease (CAD) a or documented prior Myocardial Infarction.
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.
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.
Patients aged 18 years or above
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)

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:

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).
Unexplained syncope
Current or planned implantable cardiac defibrillator (ICD)
Any condition other than cardiac disease that, in the investigator's judgment, would seriously limit life expectancy (poor survival)
Metastatic cancer
Marked valvular heart disease requiring surgical intervention
Current or planned cardiac, renal or liver transplant
Current alcohol or drug abuse
Unwilling or unable to provide informed consent
LVEF <35% with Class II-IV CHF or LVEF <30%
Participation in a clinical trial where the active treatment arm is testing an agent and/or intervention with known antiarrhythmic properties

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Heart Institute	Anchorage	Alaska	United States	99508
2	Phoenix Heart, PLLC	Glendale	Arizona	United States	85306
3	Cardiovascular Consultants	Phoenix	Arizona	United States	85032
4	Beaver Medical Group/Clinical Care Research	Banning	California	United States	92220
5	Memorial Health System	Colorado Springs	Colorado	United States	80909
6	Colorado Heart and Vascular	Denver	Colorado	United States	80204
7	Bay Area Cardiology Associates, P.A.	Brandon	Florida	United States	33511
8	University of Florida - Gainsville	Gainesville	Florida	United States	32610
9	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
10	Reliable Clinical Research	Miami	Florida	United States	33135
11	Florida Hospital	Orlando	Florida	United States	32804
12	Orlando Regional Medical Center	Orlando	Florida	United States	32806
13	Palm Beach Gardens Research Center	Palm Beach Gardens	Florida	United States	33410
14	Velella Research	Sarasota	Florida	United States	34233
15	Tallahassee Research Institute, Inc.	Tallahassee	Florida	United States	32308
16	Cardiology Associates of Palm Beach - West Palm Beach	West Palm Beach	Florida	United States	33401
17	Georgia Heart Specialist	Covington	Georgia	United States	30014
18	Northeast Georgia Heart Center, P.C.	Gainesville	Georgia	United States	30501
19	University of Chicago	Chicago	Illinois	United States	60637
20	Advocate Medical Group	Chicago	Illinois	United States	60643
21	Advocate Medical Group - Heart and Vascular of IL	Chicago	Illinois	United States	60657
22	Consultants in Cardiovascular Medicine	Melrose Park	Illinois	United States	60160
23	Community Heart and Vascular	Anderson	Indiana	United States	46011
24	Iowa Heart Center	West Des Moines	Iowa	United States	50266
25	The University of Kansas	Kansas City	Kansas	United States	66160
26	Baptist Health Lexington	Lexington	Kentucky	United States	40503
27	Leonard J. Chabert Medical Center	Houma	Louisiana	United States	70363
28	Maine Research Associates	Auburn	Maine	United States	04210
29	Maine Research Associates - Lewiston	Lewiston	Maine	United States	04240
30	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
31	Primary Care Cardiology Research	Ayer	Massachusetts	United States	01432
32	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
33	NECCR Internal Medicine and Cardiology Associates, LLC	Fall River	Massachusetts	United States	02720
34	Hawthorn Medical Associates	North Dartmouth	Massachusetts	United States	02747
35	Baystate Cardiology	Springfield	Massachusetts	United States	01199
36	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109
37	Oakwood Hospital & Medical Center	Dearborn	Michigan	United States	48124
38	McLaren Medical Center - Macomb	Mount Clemens	Michigan	United States	48043
39	Michigan Heart	Ypsilanti	Michigan	United States	48197
40	Minneapolis VA Medical Center	Minneapolis	Minnesota	United States	55417
41	University of Missouri Health Care	Columbia	Missouri	United States	65201
42	Glacier View Cardiology	Kalispell	Montana	United States	59901
43	The Cardiac Center of Creighton University	Omaha	Nebraska	United States	68131
44	Advanced Heartcare, LLC	Bridgewater	New Jersey	United States	08807
45	St. Joseph Regional Medical Center	Paterson	New Jersey	United States	07503
46	New Mexico VA Healthcare Systems	Albuquerque	New Mexico	United States	87108
47	Albany Associates Cardiology	Albany	New York	United States	12205
48	Maimonides Medical Center	Brooklyn	New York	United States	11219
49	Buffalo General Hospital/Kaleida Health	Buffalo	New York	United States	14203
50	Jamaica Hospital Medical Center	Jamaica	New York	United States	11418
51	Mid-Valley Cardiology	Kingston	New York	United States	12401
52	Winthrop-University Hospital	Mineola	New York	United States	11501
53	Gotham Cardiovascular	New York	New York	United States	10001
54	Columbia University Health Center	New York	New York	United States	10032
55	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
56	St. Elizabeth Medical Center - Hotvedt	Utica	New York	United States	13501
57	Asheville Cardiology Associates	Asheville	North Carolina	United States	28801
58	Eastern Carolina Cardiovascular	Elizabeth City	North Carolina	United States	27909
59	Northstate Clinical Research	Lenoir	North Carolina	United States	28645
60	Pinehurst Medical Clinic, Inc.	Pinehurst	North Carolina	United States	28374
61	Sanford Cardiology	Sanford	North Carolina	United States	27330
62	Wake Forest	Winston-Salem	North Carolina	United States	27157
63	Northeast Ohio Cardiovascular Specialists	Akron	Ohio	United States	44304
64	University of Cincinnati	Cincinnati	Ohio	United States	45267
65	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
66	North Ohio Research, Ltd.	Elyria	Ohio	United States	44035
67	Mercy Medical Associates	Fairfield	Ohio	United States	45014
68	Northwest Ohio Cardiology Consultants/The Toledo Hospital	Toledo	Ohio	United States	43615
69	Oklahoma City VA Medical Center Veterans Research and Education Foundation	Oklahoma City	Oklahoma	United States	73104
70	Oklahoma Foundation for Cardiovascular Research	Oklahoma City	Oklahoma	United States	73120
71	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
72	St. Luke's Bethlehem	Bethlehem	Pennsylvania	United States	18018
73	Doylestown Cardiology Associates	Doylestown	Pennsylvania	United States	18901
74	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
75	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
76	AnMed Health	Anderson	South Carolina	United States	29621
77	VA Medical Center - Charleston	Charleston	South Carolina	United States	29425
78	Carolina Cardiology Associates	Rock Hill	South Carolina	United States	29732
79	Black Hills Cardiovascular Research	Rapid City	South Dakota	United States	57701
80	Cardiovasular Research of Knoxville	Knoxville	Tennessee	United States	37917
81	Memphis VA Medical Center	Memphis	Tennessee	United States	38104
82	St. Luke's Episcopal Hospital	Houston	Texas	United States	77030
83	Non-Invasive Cardiovascular PA	Houston	Texas	United States	77074
84	Providence Health Center	Waco	Texas	United States	76712
85	Intermountain Medical Center	Murray	Utah	United States	84157
86	Cardiovascular Associates Virginia Beach	Virginia Beach	Virginia	United States	23454
87	University of Alberta	Edmonton	Alberta	Canada	T6G 2B7
88	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
89	Mississauga Clinical Research Centre	Mississauga	Ontario	Canada	L5B 2P7
90	Transcatheter Medical, Inc. Centro Cardiovascular de Caguas y del Caribe	Rio Piedras		Puerto Rico	00924