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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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CAD, CVD, Coronary Artery Disease, Angina Pectoris, Chest Pain, Cardiovascular Diseases, Coronary Heart Disease, CHD

Intervention / Treatment
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* Diagnostic Test: Corus CAD (ASGES)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerosis, Biological Markers, Molecular Genetics, Gene Expression, GES, CAD, CVD, CHD, Clinical Validity, Precision Medicine, ASGES, CT Angiography, Corus CAD, Coronary angiorgram, Age/Sex/Gene expression Score, Coronary Artery Disease, Angina Pectoris, Chest Pain, Cardiovascular Disease, Coronary Heart Disease, CTA, PREDICT