TURBULENCE: Clinical Evaluation of the CADence Device in Detection of Coronary Artery Diseases
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| CADence plus Standard Angiogram All patients who were indicated for angiogram due to results of SPECT nuclear stress test |
Diagnostic Test: CADence
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.
Other Names:
|
| CADence plus CT Angiogram All patients who were not indicated for angiogram due to results of SPECT nuclear stress test underwent CT angiogram |
Diagnostic Test: CADence
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
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:
-
Dyslipidemia: low-density lipoprotein (LDL) >130 mm/dL or high-density lipoprotein (HDL) <35 mm/dL or on treatment for dyslipidemia
-
Hypertension: blood pressure >140 millimeter of mercury (mmHg) systolic, >90 mmHg diastolic or on blood pressure altering treatment
-
Obesity: body mass index (BMI)>28
-
Current cigarette smoking
-
Diabetes: Type 1 or 2
-
Family history: coronary disease in a first or second degree relative
Exclusion criteria:
Body Mass Index (BMI)<18.5 or BMI >40
Known coronary disease as defined as:
Prior bypass surgery or coronary stenting Q-wave infarction on a past electrocardiogram (EKG) (>0.01 sec Q-wave duration in two adjacent leads)
Presence of pacemaker/defibrillator Presence of artificial valve Presence of obvious cyanotic or pre-diagnosed congenital heart defect and coarctation of the aorta Presence murmurs including valve lesions, ventricular septal defects, and arteriovenous (AV) fistulae.
Presence of moderate or severe valve disease as defined by >1/6 heart murmur on physical diagnosis Left Ventricular Assist Device (LVAD) Presence of scars on the site thorax areas Participation in trial within 30 days prior to collecting CADence data except participation in registry studies Asthma with wheezing Inability to lie flat in the supine position Acute coronary syndrome with elevated cardiac biomarkers (troponin (TP)>3x upper limit of normal (ULN) or creatine kinase MB (CKMB) >3x ULN) Heart Transplant Current cocaine use (within the past 24 hours, as reported by subject) Chronic Obstructive Pulmonary Disease (COPD) Contraindication to computed tomography (CT) angiography
-
Renal failure with glomerular filtration rate (GFR)<50 (angio risk)
-
Iodinated contrast allergy
-
Elevated heart rate which cannot be controlled sufficiently to achieve a good computed tomography angiogram
-
Body weight >350lbs.
-
Sinus rhythm rate greater than 100 beats per minute at screening.
-
Atrial fibrillation with average heart rate of greater than 70 beats per minute on resting screening electrocardiogram (ECG).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama | Birmingham | Alabama | United States | 35294 |
| 2 | Heart Center Research, LLC | Huntsville | Alabama | United States | 35801 |
| 3 | Cardiology Associates of Mobile | Mobile | Alabama | United States | 36608 |
| 4 | UCLA | Los Angeles | California | United States | 90502 |
| 5 | Hartford Hospital | Hartford | Connecticut | United States | 06102 |
| 6 | MedStar Washington Hospital Center | Washington | District of Columbia | United States | 20010 |
| 7 | Clearwater Cardiovascular | Clearwater | Florida | United States | 33756 |
| 8 | Iowa Heart Center | Des Moines | Iowa | United States | 50314 |
| 9 | MedStar Union Memorial Hospital | Baltimore | Maryland | United States | 21218 |
| 10 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 11 | Mercy Hospital | Coon Rapids | Minnesota | United States | 55433 |
| 12 | Abbott/Minneapolis Heart Institute | Minneapolis | Minnesota | United States | 55455 |
| 13 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 14 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 15 | CentraCare Heart & Vascular Center | Saint Cloud | Minnesota | United States | 56303 |
| 16 | HealthEast - St. Joseph's Hospital | Saint Paul | Minnesota | United States | 55102 |
| 17 | United Heart and Vascular Clinic | Saint Paul | Minnesota | United States | 55102 |
| 18 | Mercy Hospital St. Louis | Saint Louis | Missouri | United States | 63141 |
| 19 | Holy Name Medical Center | Teaneck | New Jersey | United States | 07666 |
| 20 | Columbia University | New York | New York | United States | 10032 |
| 21 | Mt. Sinai | New York | New York | United States | 10032 |
| 22 | North Ohio Research | Elyria | Ohio | United States | 44035 |
| 23 | Lancaster General | Lancaster | Pennsylvania | United States | 17602 |
| 24 | Jackson Clinic | Jackson | Tennessee | United States | 38301 |
Sponsors and Collaborators
- AUM Cardiovascular, Inc.
Investigators
- Study Chair: Jay Thomas, MD, University of California, Los Angeles
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1038-001
Study Results
Participant Flow
| Recruitment Details | Recruitment was held June 14, 2013 through February 10, 2016 at hospitals, clinics and research centers. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | All patients enrolled in TURBULENCE study |
| Period Title: Overall Study | |
| STARTED | 1014 |
| CADence Testing | 1013 |
| Nuclear Stress Test | 992 |
| CT and/or Standard Angiogram | 785 |
| COMPLETED | 785 |
| NOT COMPLETED | 229 |
Baseline Characteristics
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | All patients enrolled in TURBULENCE study |
| Overall Participants | 1011 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
59.14
(10.650)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
486
48.1%
|
| Male |
525
51.9%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| Caucasian |
728
72%
|
| Black or African American |
116
11.5%
|
| Hispanic or Latino |
116
11.5%
|
| Asian |
26
2.6%
|
| Native American |
7
0.7%
|
| Other |
18
1.8%
|
Outcome Measures
| Title | Sensitivity and Specificity of CADence to Detect Stenosis Relative to SPECT Performance, Using Either CT or Standard Angiogram as the Gold Standard |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol subjects who completed all required testing and had analyzable results. Both Sensitivity and Specificity were assessed in this study. |
| Arm/Group Title | Overall Study |
|---|---|
| Arm/Group Description | All patients enrolled in TURBULENCE study |
| Measure Participants | 763 |
| Sensitivity |
78
|
| Specificity |
36
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Overall Study |
|---|---|---|
| Comments | 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%). | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | 15% equivalency margin against performance of SPECT nuclear stress test OPC. Both sensitivity and specificity were measured and the equivalency margin was set the same for both parameters.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%). | |
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | Exact binomial test | |
| Comments | ||
Adverse Events
| Time Frame | Adverse events were collected from the time CADence data was collected through completion of either their standard or computed tomography (CT) angiogram. The maximum time between CADence and either standard or CT angiogram was 6 weeks. | |
|---|---|---|
| Adverse Event Reporting Description | An adverse event is considered serious if: 1) it results in death; 2) is life-threatening; 3) requires subject hospitalization or prolongation of existing hospitalization; 4) results in persistent or significant disability/incapacity; or 5) is an important medical event which may jeopardize the subject and may require medical or surgical intervention to prevent one of the previous outcomes. | |
| Arm/Group Title | Overall Study | |
| Arm/Group Description | All patients enrolled in TURBULENCE study | |
All Cause Mortality |
||
| Overall Study | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1014 (0.1%) | |
Serious Adverse Events |
||
| Overall Study | ||
| Affected / at Risk (%) | # Events | |
| Total | 8/1014 (0.8%) | |
| Cardiac disorders | ||
| Unstable Angina | 1/1014 (0.1%) | 1 |
| NSTEMI | 1/1014 (0.1%) | 1 |
| Congenital, familial and genetic disorders | ||
| Death | 1/1014 (0.1%) | 1 |
| Gastrointestinal disorders | ||
| Epigastric Pain | 1/1014 (0.1%) | 1 |
| Injury, poisoning and procedural complications | ||
| Calcaneal Fractures | 1/1014 (0.1%) | 1 |
| Surgical and medical procedures | ||
| Laryngoscopy | 1/1014 (0.1%) | 1 |
| Knee Replacement | 1/1014 (0.1%) | 1 |
| Vascular disorders | ||
| Pulmonary Embolism | 1/1014 (0.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Overall Study | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/1014 (1%) | |
| Cardiac disorders | ||
| CCTA-symptomatic bradycardia | 1/1014 (0.1%) | 1 |
| Pleurisy | 1/1014 (0.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| CCTA-respiratory | 1/1014 (0.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| CCTA-rash/hives | 2/1014 (0.2%) | 2 |
| Surgical and medical procedures | ||
| CCTA-IV contrast infiltration | 5/1014 (0.5%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Joseph Thomas, MD |
|---|---|
| Organization | UCLA Biomed |
| Phone | 310-222-2544 |
| jthomas@labiomed.org |
- 1038-001