Clinical trial NCT00500617: Personalized Risk Evaluation and Diagnosis (Using Corus CAD or ASGES) in the Coronary Tree
Official title: Identification of Gene Expression Patterns in Circulating Cells That Predict the Presence of Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Angina Pectoris
Chest Pain
Cardiovascular Diseases
Coronary Heart Disease
CAD
CVD
CHD
Keywords: 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
Lead sponsor: CardioDx
Sponsor class: INDUSTRY
First posted: 2007-07-13
Enrollment: 4350
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients undergoing clinically indicated invasive coronary artery angiogram or CT angiogram.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Algorithm AUC >0.50
timeFrame: 30days
Secondary outcomes:
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Heart Institute
state: Alaska
city: Beverly Hills
country: United States
facility: CV Medical Group Southern California
state: California
city: La Jolla
country: United States
facility: Scripps HealthCare
state: California
city: Washington
country: United States
facility: Washington Hospital Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Fuqua Heart Center of Atlanta
state: Georgia
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: Allegheny Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Intermountain HealthCare
state: Utah
Study officials:
affiliation: CardioDx
name: Mark Monane, MD FACP CMQ
role: STUDY_CHAIR
References:
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 Risk Evaluation and Diagnosis in the Coronary Tree) Investigators. Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann Intern Med. 2010 Oct 5;153(7):425-34. doi: 10.7326/0003-4819-153-7-201010050-00005.
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. Atherosclerosis. 2014 Mar;233(1):284-90. doi: 10.1016/j.atherosclerosis.2013.12.045. Epub 2014 Jan 20.
citation: 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.
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 Evaluation and Diagnosis in the Coronary Tree (PREDICT) trial. Am Heart J. 2012 Sep;164(3):320-6. doi: 10.1016/j.ahj.2012.05.012. Epub 2012 Jul 24.
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 adverse cardiovascular events and interventions in the PREDICT trial. J Cardiovasc Transl Res. 2012 Jun;5(3):366-74. doi: 10.1007/s12265-012-9353-z. Epub 2012 Mar 7.
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 assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. 2011 Mar 28;4:26. doi: 10.1186/1755-8794-4-26.
citation: Daniels SE, Beineke P, Rhees B, McPherson JA, Kraus WE, Thomas GS, Rosenberg S. Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies. J Cardiovasc Transl Res. 2014 Oct;7(7):615-22. doi: 10.1007/s12265-014-9583-3. Epub 2014 Aug 14.