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

Coronary Artery Disease Clinical Trial

— PREDICT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00500617
• Other study ID #: CDX_000004
• Secondary ID: PREDICT
• Status: Completed
• Start date: July 2007
• Est. completion date: September 2011

Study information

• Verified date: January 2019
• Source: CardioDx
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4350
• Est. completion date: September 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

Inclusion Criteria:

• Referral for a coronary angiogram (either invasive X-ray angiography or coronary CTA)

• Any one of the following clinical syndromes:

1. chest pain syndrome, stable angina, or anginal equivalent suggesting myocardial ischemia

2. low-risk unstable angin, or

3. 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

Related Conditions & MeSH terms

• Angina Pectoris
• CAD
• Cardiovascular Diseases
• CHD
• Chest Pain
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• CVD
• Heart Diseases
• Myocardial Ischemia

Intervention

Diagnostic Test:
• Corus CAD (ASGES)
Age/Sex/Gene Expression Score - ASGES

Locations

Country	Name	City	State
United States	Alaska Heart Institute	Anchorage	Alaska
United States	Fuqua Heart Center of Atlanta	Atlanta	Georgia
United States	CV Medical Group Southern California	Beverly Hills	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Scripps HealthCare	La Jolla	California
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Allegheny Hospital	Pittsburgh	Pennsylvania
United States	Intermountain HealthCare	Salt Lake City	Utah
United States	Washington Hospital Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
CardioDx

Country where clinical trial is conducted

United States, 

References & Publications (6)

Beineke P, Fitch K, Tao H, Elashoff MR, Rosenberg S, Kraus WE, Wingrove JA; PREDICT Investigators. A whole blood gene expression-based signature for smoking status. BMC Med Genomics. 2012 Dec 3;5:58. doi: 10.1186/1755-8794-5-58. — View Citation

Elashoff MR, Wingrove JA, Beineke P, Daniels SE, Tingley WG, Rosenberg S, Voros S, Kraus WE, Ginsburg GS, Schwartz RS, Ellis SG, Tahirkheli N, Waksman R, McPherson J, Lansky AJ, Topol EJ. Development of a blood-based gene expression algorithm for assessme — View Citation

Lansky A, Elashoff MR, Ng V, McPherson J, Lazar D, Kraus WE, Voros S, Schwartz RS, Topol EJ. A gender-specific blood-based gene expression score for assessing obstructive coronary artery disease in nondiabetic patients: results of the Personalized Risk Ev — View Citation

Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, Sager PT, Sehnert AJ, Yau M, Kraus WE, Newby LK, Schwartz RS, Voros S, Ellis SG, Tahirkheli N, Waksman R, McPherson J, Lansky A, Winn ME, Schork NJ, Topol EJ; PREDICT (Personalized — View Citation

Rosenberg S, Elashoff MR, Lieu HD, Brown BO, Kraus WE, Schwartz RS, Voros S, Ellis SG, Waksman R, McPherson JA, Lansky AJ, Topol EJ; PREDICT Investigators. Whole blood gene expression testing for coronary artery disease in nondiabetic patients: major adve — View Citation

Voros S, Elashoff MR, Wingrove JA, Budoff MJ, Thomas GS, Rosenberg S. A peripheral blood gene expression score is associated with atherosclerotic Plaque Burden and Stenosis by cardiovascular CT-angiography: results from the PREDICT and COMPASS studies. At — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Algorithm AUC >0.50	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).	30days