IMPACT-PCP: PCP Use of a Gene Expression Test (Corus CAD or ASGES) in Coronary Artery Disease Diagnosis

• Sponsor: CardioDx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01594411
• Collaborator: (none)
• Enrollment: 251
• Locations: 4
• Duration (Months): 10.1
• Patients Per Site: 62.8
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

This is a prospective, multi-center study examining the clinical impact of the Corus CAD (Age/Sex/Gene Expression score - ASGES) assay in approximately 250 evaluable subjects with no history of obstructive coronary artery disease who now present with chest pain or anginal-equivalent symptoms to a primary care physician (PCP) for evaluation.

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

Detailed Description

In symptomatic patients with or without prior cardiac testing, the PCP will initially decide the subject's pretest probability for coronary artery disease (CAD) based on the subject's risk factors and quality of chest pain (typical or atypical), or anginal equivalent (e.g., jaw, arm pain, or unexplained shortness of breath) and consider the results of prior testing, if applicable. The initial questionnaire will capture the PCP's initial clinical impression and decision ('preliminary decision') on how to further evaluate and manage the patient. A Corus CAD (Age/Sex/Gene Expression score - ASGES) assay will be performed at the PCP's office. After the PCP has received the Corus CAD (ASGES) result (approximately 2-3 days later), the PCP will decide on the appropriate evaluation and management of the patient ('final decision') using the Corus CAD (ASGES) result in conjunction with his/her clinical impression and/or other clinical data available. The primary aim of this study is to evaluate whether the Corus CAD (ASGES) test results is associated with a change in the PCPs' diagnostic evaluation and management of patients as compared to their initial testing and treatment decisions.

Since it takes approximately two days for the physician to receive the result of the Corus CAD (ASGES), symptomatic subjects with unstable angina, or suspicion for myocardial infarction will be excluded from the study.

A follow-up phone call and a detailed questionnaire will be performed at 30 + 15 days, from the time of blood draw, to assess the triage decision, such as referral to any subspecialists (cardiologist, gastroenterologist, and pulmonologist), cardiac diagnostic tests performed, cardiac procedures performed, and results of these cardiac tests and procedures.

Study Design

• Study Type: Observational
• Actual Enrollment: 251 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Investigation of a Molecular Personalized Coronary Gene Expression Test (Corus CAD or ASGES) on Primary Care Practice Pattern
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
All subjects Subjects are enrolled at multiple participating primary care practices. The main inclusion criterion for enrollment is the occurrence of chest pain (or anginal equivalent) in a patient without known significant coronary artery disease (CAD) or a history of prior myocardial infarction.	Diagnostic Test: Corus CAD; Age/Sex/Gene Expression Score (ASGES)

Outcome Measures

Primary Outcome Measures

1. Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score [pre- and post- gene expression testing results (on average 2-3 days to receive ASGES)]

   The primary objective was to assess whether the Age/Sex/Gene Expression Score (ASGES) altered clinicians' evaluations, defined by a change in patient management from preliminary to final decision. The change was prospectively defined as a downgrade or upgrade in intensity of the diagnostic plan based on the following hierarchical categories:(1) no further cardiac testing or treatment, (2) lifestyle changes or medical therapy, (3) stress testing (with or without imaging) or computed tomography/coronary angiography, or (4) invasive coronary angiography. The ASGES algorithm comprises expression values for 23 genes from peripheral blood cells in 6 terms, patient age, and sex. The changes in gene expression are quantified using an algorithm that generates a ASGES ranging from 1 to 40. A score <=15 indicates a low risk of underlying obstructive coronary disease. The ASGES has a negative predictive value of 96% for ASGES <=15 in a population referred to myocardial perfusion imaging.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Stable chest pain, typical or atypical angina or anginal equivalent

2. The patient has signed the appropriate Institutional Review Board approved Informed Consent Form.

Exclusion Criteria:

1. History of myocardial infarction

2. Current Myocardial infarction (MI) or acute coronary syndrome.

3. Current New York Heart Association (NYHA) class III or IV congestive heart failure symptoms.

4. Any previous coronary revascularization.

5. Any individuals with :

• Diabetes

• Suspected unstable angina

• Systemic infections

• Systemic inflammatory conditions

1. Any individuals currently taking:

• Steroids

• Immunosuppressive agents

• Chemotherapeutic agents

1. Any Major Surgery within 2 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John's Creek Primary Care	Suwanee	Georgia	United States	30024
2	The Lipid Center	Baton Rouge	Louisiana	United States	70809
3	Carolina Family Healthcare	Charlotte	North Carolina	United States	28277
4	Family Care Clinic	Bonham	Texas	United States	75418

Sponsors and Collaborators

• CardioDx

Investigators

• Study Director: May Yau, MS, CardioDx

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: CardioDx
• ClinicalTrials.gov Identifier: NCT01594411
• Other Study ID Numbers: CDX_000014; IMPACT-PCP
• First Posted: May 9, 2012
• Last Update Posted: Jan 31, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by CardioDx: Corus CAD; ASGES; Age/Sex/Gene Expression Score; Gene Expression; GES; CAD; CVD; CHD; Clinical Utility; Precision Medicine; Primary care; Coronary Artery Disease; Angina Pectoris; Chest Pain; Cardiovascular Disease; Coronary Heart Disease; IMPACT; IMPACT-PCP
• Additional relevant MeSH terms: Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Angina Pectoris; Chest Pain

Study Results

Participant Flow

Recruitment Details	Subjects are enrolled at multiple participating primary care practices from site initiation (Apr-Jun 2012) thru January 2013.
Pre-assignment Detail	327 screened, 275 met inclusion/exclusion. Subjects were excluded from the analysis set if no Corus CAD test could be resulted (7) or if additional information was available and used in making post treatment decisions (3) or did not inclusion/exclusion (discovered after research blood sample draw). Analysis set was 251.

Arm/Group Title	All Subjects With Corus CAD
Arm/Group Description	Subjects are enrolled at multiple participating primary care practices. The main inclusion criterion for enrollment and being tested with Corus CAD is the occurrence of chest pain (or anginal equivalent) in a patient without known significant CAD or a history of prior myocardial infarction.
Period Title: Overall Study
STARTED	251
COMPLETED	249
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	Subjects are enrolled at multiple participating primary care practices. The main inclusion criterion for enrollment is the occurrence of chest pain (or anginal equivalent) in a patient without known significant CAD or a history of prior myocardial infarction.
Overall Participants	251
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	182 72.5%
>=65 years	69 27.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.2 (13)
Sex: Female, Male (Count of Participants)
Female	140 55.8%
Male	111 44.2%
Region of Enrollment (participants) [Number]
United States	251 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.7 (6.7)
Age/Sex/Gene Expression Score (unitless) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [unitless]	16 (10)

Outcome Measures

1. Primary Outcome

Title	Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score
Description	The primary objective was to assess whether the Age/Sex/Gene Expression Score (ASGES) altered clinicians' evaluations, defined by a change in patient management from preliminary to final decision. The change was prospectively defined as a downgrade or upgrade in intensity of the diagnostic plan based on the following hierarchical categories:(1) no further cardiac testing or treatment, (2) lifestyle changes or medical therapy, (3) stress testing (with or without imaging) or computed tomography/coronary angiography, or (4) invasive coronary angiography. The ASGES algorithm comprises expression values for 23 genes from peripheral blood cells in 6 terms, patient age, and sex. The changes in gene expression are quantified using an algorithm that generates a ASGES ranging from 1 to 40. A score <=15 indicates a low risk of underlying obstructive coronary disease. The ASGES has a negative predictive value of 96% for ASGES <=15 in a population referred to myocardial perfusion imaging.
Time Frame	pre- and post- gene expression testing results (on average 2-3 days to receive ASGES)

Outcome Measure Data

Analysis Population Description

The study sites included 9 clinicians at 4 community-based primary care practices who assessed all participants with a valid ASGES.

Arm/Group Title	No Tests/Treatment	Medical Therapy	Stress Test	Invasive Angiography
Arm/Group Description	Physician decision for no additional tests or cardiac treatment after receiving patients' GES	Physician decision for lifestyle changes or medical therapy after receiving patients' GES	Physician decision for stress testing (with or without imaging) or computed tomography/coronary angiography after receiving patients' GES	Physician decision for invasive coronary angiography after receiving patients' GES
Measure Participants	123	22	104	2
No Tests/Treatment pre-ASGES, ASGES <=15 (n=40)	38	1	1	0
NoTests/Treatment pre-ASGES, ASGES >15 (n=43)	3	1	39	0
Medical Therapy pre-ASGES, ASGES ,=15 (n=33)	25	7	1	0
Medical Therapy pre-ASGES, ASGES >15 (n=15)	5	2	7	1
Stress Tes pre-ASGES, ASGES <=15 (N=53)	45	5	3	0
Stress test pre-ASGES, ASGES >15 (n=65)	5	6	53	1
Invasive Coronary Angio pre-ASGES, AGES >=15 (n=1)	1	0	0	0
Invasive Coronary Angio pre-ASGES, ASGES >15 (n=1)	1	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	No Tests/Treatment
	Comments	The proportion of patients whose final treatment plan changes from the preliminary will be estimated, and a one-sided binomial test with alpha level of .05 will be used to test whether it is greater than 10%. This is the level at which it is assumed that patient management has been modified by a practically important amount.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	one-sided binomial with alpha level of 0
	Comments

Adverse Events

Arm/Group Title	All Subjects
Arm/Group Description	Subjects are enrolled at multiple participating primary care practices. The main inclusion criterion for enrollment is the occurrence of chest pain (or anginal equivalent) in a patient without known significant CAD or a history of prior myocardial infarction.
All Cause Mortality
	All Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/251 (0%)
Other (Not Including Serious) Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/251 (0%)

Limitations/Caveats

Prospective design may have influenced the diagnostic strategy; but historical controls had a similar diagnostic strategy. Possible Selection bias; we believe these pts are typical of each practice. Appropriateness of care not evaluated

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

CardioDx will provide a copy of the proposed publication to Collaborator for prior review for a thirty (30)-day period, during which period any Collaborator personnel listed as authors may either (a) elect to opt out from being listed as an author, or (b) suggest modifications to the proposed publication, and if they do not elect either (a) or (b) within that period, they will be deemed to have consented to publication as an author.