Coronary Artery Disease
Conditions
Keywords
Coronary Artery Disease, Nuclear Stress Test, CT Angiography, Angiography, CADence
Brief summary
This is a multi-center, prospective, non-randomized, double-blinded trial to evaluate the sensitivity and specificity of the CADence device in detecting the existence of clinically significant coronary artery disease as determined by either standard or CT angiography.
Detailed description
This is a multi-center, prospective, non-randomized, double-blinded, trial to evaluate the performance of the CADence in detecting the existence of at least one major coronary artery with clinically significant stenosis in a subject is defined as the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex , proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries. Consented subjects will be evaluated with the CADence device and then undergo nuclear stress testing followed by either computed tomography or standard coronary angiography. The maximum expected timeframe between CADence and computed tomography Angiography or standard angiography is 6 weeks. This is a double-blinded study. All physicians and subjects will be masked to the diagnostic results of the CADence until completion of CADence, nuclear stress, computed tomography or standard coronary angiogram testing for the subjects. Patient care will not be based on the CADence results. Study participation will conclude after the computed tomography angiography or standard coronary angiography procedure. computed tomograph or standard coronary angiography are considered acceptable clinical reference standards in this study and are gold standards for detection of coronary artery disease. The experimental unit of this study is the subject. Existence of clinically significant coronary artery disease in a subject is defined as the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries. The study required sample size is 826 but may enroll up to 1,300 subjects. The sensitivity and specificity of the CADence are expected to be 80% and 73% respectively. Observed sensitivity and specificity will be compared to nuclear stress literature-based performance standards of 83% and 80% respectively using one sample non-inferiority binomial tests with a non-inferiority margin of 15 percentage points. Sample size requirements are 109 subjects with the presence of at least one lesion with ≥ ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left MAIN coronary arteries. to test the sensitivity hypothesis and 268 subjects without the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left MAIN coronary arteries. to test the specificity hypothesis. It was assumed that 15 percent of enrolled subjects would be found to have the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries. In order to accrue 109 subjects with significant Coronary Artery Disease as defined in the protocol, 826 subjects must be enrolled. Sample sizes provide 85% power with alpha of 0.05 for each statistical test.
Interventions
DIAGNOSTIC_TESTCADence
Patients with chest pain and two or more coronary risk factors and who were already indicated for nuclear stress test were enrolled in the study. The CADence was performed prior to nuclear stress test. Patients underwent standard angiogram based upon normal clinical judgement. In all other patients a CT angiogram followed. CADence is a handheld equipped with acoustic sensor technology, a patient booklet, remote algorithm and final report.
Sponsors
AUM Cardiovascular, Inc.
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects clinically indicated for nuclear stress test and who satisfy all the inclusion and
Exclusion criteria
are eligible for participation. Inclusion criteria: Age 22 years or older Willing and able to give informed consent Clinical indication for nuclear stress test evaluation Chest pain syndrome Two or more coronary artery disease risk factors as defined by: 1. Dyslipidemia: low-density lipoprotein (LDL) \>130 mm/dL or high-density lipoprotein (HDL) \<35 mm/dL or on treatment for dyslipidemia 2. Hypertension: blood pressure \>140 millimeter of mercury (mmHg) systolic, \>90 mmHg diastolic or on blood pressure altering treatment 3. Obesity: body mass index (BMI)\>28 4. Current cigarette smoking 5. Diabetes: Type 1 or 2 6. Family history: coronary disease in a first or second degree relative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity of CADence to Detect Stenosis Relative to SPECT Performance, Using Either CT or Standard Angiogram as the Gold Standard | No more than 3 weeks between CADence, SPECT and standard or CT angiogram | The CADence will be considered to have demonstrated effectiveness in detecting the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending (pLAD), mid Left anterior Descending (mLAD), proximal Left Circumflex (pLCx), mid Left Circumflex (mLCx), proximal Right Coronary Artery (pRCA), mid Right Coronary Artery (mRCA), distal Right Coronary Artery (dRCA) and Obtuse Margin 1 (OM1), Obtuse Margin 2 (OM2), and Ramus Intermedius (RI) if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries if sensitivity and specificity are non-inferior within 15 percentage points to a sensitivity of 83% and a specificity of 80%, which is the literature-based Objective Performance Criteria (OPC) for nuclear stress tests. |
Countries
United States
Participant flow
Recruitment details
Recruitment was held June 14, 2013 through February 10, 2016 at hospitals, clinics and research centers.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All patients enrolled in TURBULENCE study | 1,011 |
| Total | 1,011 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 66 |
| Overall Study | Physician Decision | 40 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 121 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 59.14 years STANDARD_DEVIATION 10.65 |
| Race/Ethnicity, Customized Race/Ethnicity Asian | 26 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black or African American | 116 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian | 728 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino | 116 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Native American | 7 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other | 18 Participants |
| Sex: Female, Male Female | 486 Participants |
| Sex: Female, Male Male | 525 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1,014 |
| other Total, other adverse events | 10 / 1,014 |
| serious Total, serious adverse events | 8 / 1,014 |
Outcome results
Primary
Sensitivity and Specificity of CADence to Detect Stenosis Relative to SPECT Performance, Using Either CT or Standard Angiogram as the Gold Standard
The CADence will be considered to have demonstrated effectiveness in detecting the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending (pLAD), mid Left anterior Descending (mLAD), proximal Left Circumflex (pLCx), mid Left Circumflex (mLCx), proximal Right Coronary Artery (pRCA), mid Right Coronary Artery (mRCA), distal Right Coronary Artery (dRCA) and Obtuse Margin 1 (OM1), Obtuse Margin 2 (OM2), and Ramus Intermedius (RI) if segment diameter \>2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries if sensitivity and specificity are non-inferior within 15 percentage points to a sensitivity of 83% and a specificity of 80%, which is the literature-based Objective Performance Criteria (OPC) for nuclear stress tests.
Time frame: No more than 3 weeks between CADence, SPECT and standard or CT angiogram
Population: Per protocol subjects who completed all required testing and had analyzable results. Both Sensitivity and Specificity were assessed in this study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Sensitivity and Specificity of CADence to Detect Stenosis Relative to SPECT Performance, Using Either CT or Standard Angiogram as the Gold Standard | Sensitivity | 78 percent |
| Overall Study | Sensitivity and Specificity of CADence to Detect Stenosis Relative to SPECT Performance, Using Either CT or Standard Angiogram as the Gold Standard | Specificity | 36 percent |
Comparison: The goal was to test the Sensitivity and specificity of CADence as compared to SPECT nuclear stress test OPC. Both were measured and reported in this study. The Sensitivity of CADence was 78% (95% CI 76.1-90.8%) while the specificity was 36% (95% CI 32-39%).p-value: 0.012Exact binomial test