PROspective Multicenter Imaging Study for Evaluation of Chest Pain

Study Overview
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Brief Summary
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A prospective multicenter imaging study for evaluation of chest pain. Objective is to determine whether an initial non-invasive anatomic imaging strategy with coronary CT angiography (CTA) will improve clinical outcomes in subjects with symptoms concerning for coronary artery disease relative to an initial functional testing strategy (usual care). Study hypothesis: initial anatomic testing strategy will provide information that will result in superior long-term health outcomes as compared to an initial functional testing strategy.

Detailed Description
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Pragmatic randomized trial of clinical effectiveness of diagnostic testing strategies for coronary artery disease (CAD), to be performed in outpatient settings including acute and primary care and cardiology offices. Qualifying patients presenting with new or worsening symptoms suspicious for clinically significant CAD who require diagnostic testing and have not been previously evaluated will be randomized to an initial strategy of either anatomic or functional testing. All subsequent decisions regarding additional testing, medications and/or procedures will be at the discretion of the responsible clinical care team Within the functional testing arm, the subject's care team will select the specific test to be performed (exercise electrocardiogram (ECG), stress nuclear, or stress echocardiogram (echo)) consistent with 'usual care' in that practice setting. The subject's care team will be provided with 'Information sheets' summarizing current standards for test interpretation and preventive care, but specific medical treatment will not be mandated by the trial.

Official Title
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PROspective Multicenter Imaging Study for Evaluation of Chest Pain - The PROMISE Trial

Conditions
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Chest Pain

Intervention / Treatment
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* Procedure: Coronary Angiography
* Procedure: Stress Echocardiogram
* Procedure: Nuclear Stress Test
* Procedure: Exercise Electrocardiogram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: new or worsening chest pain suspicious for clinically significant coronary artery disease (CAD) no prior evaluation for this episode of symptoms planned non-invasive testing for diagnosis men age ≥55 years men age ≥45 years with increased probability of coronary artery disease (CAD) due to either (A. Diabetes Mellitus (DM) requiring medical treatment OR Peripheral Arterial Disease (PAD) defined as documented >50% peripheral arterial stenosis treated medically or invasively OR cerebrovascular disease (stroke, documented > 50% carotid stenosis treated medically or invasively) OR B. At least one of the following cardiovascular risk factors: 1-Ongoing tobacco use, 2-Hypertension, 3-Abnormal ankle brachial index (ABI) defined as less than <0.9, 4-Dyslipidemia women age ≥65 years women age ≥50 years with increased probability of coronary artery disease (CAD) due to either (A. Diabetes Mellitus (DM) requiring medical treatment OR Peripheral Arterial Disease (PAD) defined as documented >50% peripheral arterial stenosis treated medically or invasively OR cerebrovascular disease (stroke, documented > 50% carotid stenosis treated medically or invasively) OR B. At least one of the following cardiovascular risk factors: 1-Ongoing tobacco use, 2-Hypertension, 3-Abnormal ankle brachial index (ABI) defined as less than <0.9, 4-Dyslipidemia Serum creatinine ≤ 1.5 mg/dL within the past 90 days Negative urine/serum pregnancy test for female subjects of child-bearing potential Exclusion Criteria: Diagnosed or suspected acute coronary syndrome (ACS) requiring hospitalization or urgent or emergent testing; Elevated troponin or creatine kinase-myocardial band (CK-MB) Hemodynamically or clinically unstable condition systolic blood pressure (BP) < 90 mmHg, atrial or ventricular arrhythmias, or persistent resting chest pain felt to be ischemic despite adequate therapy) Known coronary artery disease (CAD) with prior Myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or any angiographic evidence of coronary artery disease (CAD) ≥50% lesion in a major epicardial vessel Any invasive coronary angiography or non-invasive anatomic or functional cardiovascular (CV) test for detection of coronary artery disease (CAD), including coronary tomographic angiography (CTA) and exercise electrocardiogram (ECG), within the previous twelve (12) months Known significant congenital, valvular (> moderate) or cardiomyopathic process (hypertrophic cardiomyopathy or reduced systolic left ventricular function (LVEF) ≤ 40%)) which could explain cardiac symptoms Contraindication to undergoing a coronary tomographic angiography (CTA), including but not limited to: a. Allergy to iodinated contrast agent, b. Unable to receive beta blockers unless heart rate < 65 beats per minute, c. Pregnancy Life expectancy < 2 years Unable to provide written informed consent or participate in long-term follow-up

Ages Eligible for Study
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Minimum Age: 45 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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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Functional diagnostic tests<br>Stress Echocardiogram Nuclear Stress Test Exercise Electrocardiogram | Procedure: Stress Echocardiogram<br>* Use of standard equipment for usual-care testing<br>Procedure: Nuclear Stress Test<br>* Use of standard equipment for usual-care testing<br>Procedure: Exercise Electrocardiogram<br>* Use of standard equipment for usual-care testing<br>|
| Active Comparator: Anatomic diagnostic test<br>Coronary Angiography | Procedure: Coronary Angiography<br>* Use of standard equipment for usual-care testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Primary Endpoint | Time to primary endpoint as defined as a composite of death, myocardial infarction (MI), major complications from cardiovascular (CV) procedures or testing, and unstable angina hospitalization. The Kaplan-Meier events rates (cumulative percentage of participants with an event) were estimated for the anatomic and functional diagnostic test groups. | 90 days, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Death, Myocardial Infarction (MI), Unstable Angina Hospitalization | Time to this secondary endpoint as defined as a composite of death, myocardial infarction (MI), and unstable angina hospitalization. The Kaplan-Meier events rates (cumulative percentage of participants with an event) were estimated for the anatomic and functional diagnostic test groups. | 90 days, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months | 
| Time to Death or Myocardial Infarction (MI) | Time to this secondary endpoint as defined as a composite of death and myocardial infarction (MI). The Kaplan-Meier events rates (cumulative percentage of participants with an event) were estimated for the anatomic and functional diagnostic test groups. | 90 days, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months | 
| Time to Major Complications From Cardiovascular (CV) Procedures | Time to this secondary endpoint as defined as a composite of major complications from cardiovascular procedures and testing (stroke, bleeding, anaphylaxis, renal failure). The Kaplan-Meier events rates (cumulative percentage of participants with an event) were estimated for the anatomic and functional diagnostic test groups. | 90 days, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months | 
| Time to Death, Myocardial Infarction (MI), Unstable Angina (UA), Complications, No Coronary Artery Disease (CAD) | Time to primary endpoint as defined as a composite of death, myocardial infarction (MI), major complications from cardiovascular (CV) procedures or testing, unstable angina hospitalization, and no coronary artery disease (CAD). The Kaplan-Meier events rates (cumulative percentage of participants with an event) were estimated for the anatomic and functional diagnostic test groups. | 90 days, 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 42 months | 
| Percentage of Invasive Cardiac Catheterization Events Without Obstructive Coronary Artery Disease Within 90 Days Following Participant Randomization | Percentage of Invasive Cardiac Catheterization Events Without Obstructive Coronary Artery Disease (CAD)Within 90 Days Following Participant Randomization | Up to 90 days following participant randomization | 
| Medical Cost | Assess and compare total medical cost for the two diagnostic testing arms by intention to treat at both 90 days and 3 years cumulative. | 90 days and 3 years cumulative | 
| Quality of Life (QOL) as Measured by Duke Activity Status Index | Participant score in Quality of Life as measured by Duke Activity Status Index (DASI). DASI measures a person's functional capacity based on a 12-item questionnaire that correlates with peak O2 uptake during exercise testing. The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity). | Baseline, 6 months, 12 months 24 months | 
| Quality of Life (QOL) as Measured by Seattle Angina Scale Anginal Frequency Subscale | Participant score Quality of Life measured by Seattle Angina Scale Anginal Frequency Subscale utilizing the Seattle Angina Questionnaire (SAQ). SAQ: 19-item, 5-6-point Likert, questionnaire measuring 5 dimensions of coronary artery disease: Anginal Stability: whether symptoms are changing. Anginal Frequency: how often patient having symptoms Physical Limitation: how much condition hampers ability to do what he wants.Treatment Satisfaction: how well patient understands care. Disease Perception: impact of condition on interpersonal relationships. Each dimension assigns response an value, beginning with 1 for response at the lowest level of functioning & summing across items within each of the 5 scales. Scale scores transformed to 0-100 range by subtracting the lowest scale. Higher score suggest symptoms more stable & less frequent, condition has less impact on activities, increased satisfaction with treatment, & perception of disease has less impact on interpersonal relationships. | Baseline, 6 month, 12 month, 24 month | 
| Quality of Life (QOL) as Measured by Seattle Anginal Quality of Life Subscale | Participant score Quality of Life measured by Seattle Angina Scale Anginal Frequency Subscale utilizing the Seattle Angina Questionnaire (SAQ). SAQ: 19-item, 5-6-point Likert, questionnaire measuring 5 dimensions of coronary artery disease: Anginal Stability: whether symptoms are changing. Anginal Frequency: how often patient having symptoms Physical Limitation: how much condition hampers ability to do what he wants.Treatment Satisfaction: how well patient understands care. Disease Perception: impact of condition on interpersonal relationships. Each dimension assigns response an value, beginning with 1 for response at the lowest level of functioning & summing across items within each of the 5 scales. Scale scores transformed to 0-100 range by subtracting the lowest scale. Higher score suggest symptoms more stable & less frequent, condition has less impact on activities, increased satisfaction with treatment, & perception of disease has less impact on interpersonal relationships. | Baseline, 6 months, 12 months, 24 months | 
| Quality of Life (QOL) as Measured by Complete Resolution of Symptoms That Led to the Initial Testing | Percentage of participants with improvement in Quality of Life as measured by complete resolution of the symptoms that led to initial testing | 6 month, 12 month 24 month | 
| Cumulative Radiation Exposure Within 90 Days | Cumulative radiation exposure from all cardiovascular diagnostic tests and procedures performed within 90 days after randomization. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chest pain, coronary artery disease, CAD