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

Completed

• Conditions: Chest Pain; Coronary Heart Disease; CVD; Coronary Artery Disease; CAD; CHD; Angina Pectoris; Cardiovascular Diseases
• Interventions: Diagnostic Test: Corus CAD (ASGES)

• Registration Number: NCT00500617
• Lead Sponsor: CardioDx

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.

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 Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-07-11
• Study First Submitted QC: 2007-07-11
• Study First Posted: 2007-07-13
• Primary Completion: 2010-01
• Study Completion: 2011-09
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-29
• Last Update Posted: 2019-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4350

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
segment 1	Corus CAD (ASGES)	Gene discovery blood draw
sement 2	Corus CAD (ASGES)	Assay development blood draw
segment 3	Corus CAD (ASGES)	Assay validation blood draw
segment 4	Corus CAD (ASGES)	Additional assay testing blood draw (Note: post discovery diabetic subjects assigned to this group)

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (10)

Alaska Heart Institute; 🇺🇸 Anchorage, Alaska, United States

CV Medical Group Southern California; 🇺🇸 Beverly Hills, California, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Intermountain HealthCare; 🇺🇸 Salt Lake City, Utah, United States

Scripps HealthCare; 🇺🇸 La Jolla, California, United States

Washington Hospital Medical Center; 🇺🇸 Washington, District of Columbia, United States

Fuqua Heart Center of Atlanta; 🇺🇸 Atlanta, Georgia, United States

Allegheny Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Minneapolis Heart Institute; 🇺🇸 Minneapolis, Minnesota, United States