PREDICT: Personalized Risk Evaluation and Diagnosis (Using Corus CAD or ASGES) in the Coronary Tree

Sponsor

CardioDx (Industry)

Overall Status

Completed

CT.gov ID

NCT00500617

Collaborator

(none)

4,350

Enrollment

Locations

Duration (Months)

435

Patients Per Site

8.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The PREDICT study is to develop and validate a diagnostic blood ASGES (age, sex, gene expression score) or Corus CAD for atherosclerotic coronary artery disease (CAD). The Corus CAD (Age/Sex/Gene Expression score - ASGES) will use quantitative real-time PCR (RT-PCR) to quantify the expression of multiple genes from circulating peripheral blood cells to assess the presence of clinically significant CAD in a patient.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Angina Pectoris Chest Pain Cardiovascular Diseases Coronary Heart Disease CAD CVD CHD	Diagnostic Test: Corus CAD (ASGES)

Detailed Description

The purpose of the PREDICT study is to develop and validate a diagnostic blood ASGES (age, sex, gene expression score) or Corus CAD for atherosclerotic coronary artery disease (CAD). The Corus CAD (Age/Sex/Gene Expression score - ASGES) will use quantitative real-time PCR (RT-PCR) to quantify the expression of multiple genes from circulating peripheral blood cells to assess the presence of clinically significant CAD in a patient.

This is a prospective, multi-center, observational study. Participation in the study does not alter clinical care. The only procedure required by the protocol is collection of a research blood sample. All other data collected will be in accordance with each participating institution's standard patient care.

The study is divided into four sequential segments with unique subjects and goals: ASGES (Corus CAD) discovery (segment 1), ASGES (Corus CAD) development (segment 2), ASGES (Corus CAD) validation (segment 3), and additional ASGES (Corus CAD) testing (segment 4). The primary analysis will be performed during the third segment of the study using a subset of the enrolled subjects ("primary subjects"). Primary subjects will be defined by additional eligibility criteria beyond the general eligibility criteria required for enrollment in the overall study. The additional, post-enrollment eligibility criteria will be based on clinical and demographic factors that are found during the course of the study to affect the expression of genes used in the ASGES (Corus CAD). Such factors will be identified during gene discovery and algorithm development. The post-enrollment eligibility criteria will be defined prior to the beginning of the ASGES (Corus CAD) validation segment of the study.

In addition, three substudies are planned and will enroll up to 1500 subjects.

The first substudy will include subjects undergoing cardiac CT angiography (CTA) and aims to determine how gene expression correlates with total coronary atheroma burden, as measured by CTA.
The second substudy examines sample handling and shipping conditions and does not affect the treatment of the subjects.
The third substudy will focus on additional algorithm development and validation in a non-diabetic female patient population.

Study Design

Study Type:

Observational

Actual Enrollment :

4350 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Identification of Gene Expression Patterns in Circulating Cells That Predict the Presence of Coronary Artery Disease

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
segment 1 Gene discovery blood draw	Diagnostic Test: Corus CAD (ASGES) Age/Sex/Gene Expression Score - ASGES
sement 2 Assay development blood draw	Diagnostic Test: Corus CAD (ASGES) Age/Sex/Gene Expression Score - ASGES
segment 3 Assay validation blood draw	Diagnostic Test: Corus CAD (ASGES) Age/Sex/Gene Expression Score - ASGES
segment 4 Additional assay testing blood draw (Note: post discovery diabetic subjects assigned to this group)	Diagnostic Test: Corus CAD (ASGES) Age/Sex/Gene Expression Score - ASGES

Outcome Measures

Primary Outcome Measures

Algorithm AUC >0.50 [30days]
The primary analysis will be performed during the third segment of the study using a subset of the enrolled subjects ("primary subjects"). The primary endpoint for the PREDICT study is a validated algorithm that can accurately classify subjects with and without any coronary artery lesion with a ≥50% diameter stenosis, as measured by Core Laboratory blinded quantitative coronary angiography. In evaluating this endpoint, subjects will be classified as either cases or controls. The endpoint will be assessed by calculating the area under the curve (AUC) for the algorithm score, and testing against an AUC = 0.50 to determine clinical utility, using an alpha level of 0.05 (two-sided).

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Referral for a coronary angiogram (either invasive X-ray angiography or coronary CTA)
Any one of the following clinical syndromes:

chest pain syndrome, stable angina, or anginal equivalent suggesting myocardial ischemia
low-risk unstable angin, or
asymptomatic individuals with a high probability of CAD

Exclusion Criteria:

History of myocardial infarction or known CAD
Current Myocardial Infarct (MI), acute coronary syndrome with high-risk features or unstable angina with high-risk features
New York Heart Association (NYHA) class III or IV congestive
Inability to give informed congestive heart failures
Severe left ventricular systolic dysfunction (LVEF<35%)
Severe regurgitant or stenotic cardiac valve lesion
Active or chronic systemic infection
Rheumatologic, autoimmune or hematologic conditions
Any organ transplant
Immunosuppressive therapy
Chemotherapy in the preceding year
Major blood or blood product transfusion in the preceding 2 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Heart Institute	Anchorage	Alaska	United States	99508
2	CV Medical Group Southern California	Beverly Hills	California	United States	90210
3	Scripps HealthCare	La Jolla	California	United States	92037
4	Washington Hospital Medical Center	Washington	District of Columbia	United States	20010
5	Fuqua Heart Center of Atlanta	Atlanta	Georgia	United States	30309
6	Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407
7	Duke University Medical Center	Durham	North Carolina	United States	27705
8	Allegheny Hospital	Pittsburgh	Pennsylvania	United States	15212
9	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
10	Intermountain HealthCare	Salt Lake City	Utah	United States	84107