Clinical Evaluation of the CADence Device in Detection of Coronary Artery Diseases (TURBULENCE)

Pivotal Study of the CADence Device in Detection of Coronary Artery Diseases

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: CADence

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 Type: Observational
• Enrollment (Actual): 1014

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC
    • Mobile, Alabama, United States, 36608
      • Cardiology Associates of Mobile
  • California
    • Los Angeles, California, United States, 90502
      • UCLA
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iowa Heart Center
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • MedStar Union Memorial Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Abbott/Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Heart & Vascular Center
    • Saint Paul, Minnesota, United States, 55102
      • United Heart and Vascular Clinic
    • Saint Paul, Minnesota, United States, 55102
      • HealthEast - St. Joseph's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital St. Louis
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10032
      • Mt. Sinai
  • Ohio
    • Elyria, Ohio, United States, 44035
      • North Ohio Research
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General
  • Tennessee
    • Jackson, Tennessee, United States, 38301
      • Jackson Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All enrolled subjects that received nuclear stress testing and either CT or standard coronary angiography after the CADence evaluation will be included in the analysis.

Description

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

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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: CT Angiogram; Angiogram; Nuclear Stress Test
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: CT Angiogram; Angiogram; Nuclear Stress Test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	No more than 3 weeks between CADence, SPECT and standard or CT angiogram

Collaborators and Investigators

• Sponsor: AUM Cardiovascular, Inc.
• Investigators: Study Chair: Jay Thomas, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2013
• Primary Completion (Actual): February 10, 2016
• Study Completion (Actual): February 10, 2016

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Actual): July 10, 2020
• Last Update Submitted That Met QC Criteria: July 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Angiography; CT Angiography; Nuclear Stress Test; CADence
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 1038-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No