Clinical trial NCT02178904: Dual Energy CT for Ischemia Determination Compared to "Gold Standard" Non-Invasive and Invasive Techniques
Official title: Dual Energy Computed Tomography for Ischemia Determination Compared to "Gold Standard" Non-Invasive and Invasive Techniques
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ischemia
Keywords: Ischemia
Dual Energy Computed Tomography
Computed Tomographic Perfusion
Fractional Flow Rate
Invasive Coronary Angiography
Coronary Artery Stenosis
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2014-07-01
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Hospitals in Argentina, Beijing, Seattle, Vancouver, New York

Brief summary: The purpose of this study is determine the diagnostic performance of dual energy computed tomography perfusion for non-invasive assessment of the hemodynamic significance of coronary stenosis, as compared to a direct measurement of fraction flow reserve during cardiac catheterization as a reference standard.

The overall objective of the present study is to determine the diagnostic performance of dual energy computed tomography perfusion for non-invasive assessment of the hemodynamic significance of coronary stenosis, as compared to direct measurement of fraction flow reserve during cardiac catheterization as a reference standard.

Detailed description: Coronary artery disease is the leading cause of morbidity and mortality in the United States. At present, professional guidelines endorse the use of an array of non-invasive tests for patients with suspected coronary artery disease, which are limited to one of two approaches: 1) physiologic demonstration of ischemia by functional stress testing or 2) anatomic visualization of stenosis by coronary computed tomographic angiography.

Stress test for physiologic assessment of coronary disease is performed most commonly with the prognostic value unsurpassed by other non-invasive tests, with risk of cardiac events escalating exponentially with increasing inducible hypoperfusion. However, despite its high reported performance, the "real world" accuracy of stress test is less sanguine and demonstrates generally poor discrimination of specific vessels that accommodate coronary lesions that cause ischemia. These findings have encouraged the adoption of other stress tests, such as positron emission tomography, which offers reliable attenuation correction, increased count sensitivity, lower radiation dose and enhanced diagnostic performance. Positron emission tomography also enables measures of absolute myocardial blood flow.

Coronary computed tomographic angiography is an alternative test that evaluates coronary disease by direct anatomic visualization of stenoses in a manner similar to cardiac catheterization. Similarly, when employing invasive fractional flow reserve to identify ischemia, high-grade stenoses observed by computed tomography are causal of ischemia less than half of the time.

Multicenter randomized trial data examining invasive methods have demonstrated that a combined anatomic-physiologic approach by catheterization with fractional flow reserve improves identification of patients who may benefit from revascularization, by restricting revascularization to those with high-grade stenoses that specifically cause ischemia. Nevertheless, the combination of catheterization with fractional flow reserve is invasive, is not widely adopted in clinical practice, and is costly.

Computed tomography perfusion is a novel non-invasive technique that can evaluate the physiologic significance of coronary disease, and is performed by adding a single image acquisition to computed tomography in the same setting. The combination of computed tomography perfusion to computed tomography may represent an ideal "one-stop shop" that may allow for both anatomic and physiologic evaluation of coronary disease, serve as a more effective gatekeeper to cardiac catheterization, and better identify patients that would benefit from revascularization.

The emergence of dual energy computed tomography techniques enables potentially improved perfusion assessment. In particular, projection-based dual energy computed tomography is a novel computed tomography method that incorporates energy-dependent models for basis material decomposition within tissue, and may allow for absolute quantification of myocardial blood \[iodine\] volume with high accuracy and allows for single energy monochromatic imaging that retains image stability while reducing common computed tomography artifacts. Both of these measures by projection-based dual energy computed tomography enable quantitative assessment of myocardial iodine uptake, but the diagnostic performance of dual energy computed tomography as compared to nuclear stress testing has not been tested systematically to date.

To date, an integrated anatomic-physiologic approach by non-invasive methods has been lacking, largely due to the lack of a test that is capable of providing both accurate anatomic and physiologic data in a single setting.

The DECIDE-Gold trial will be a prospective multicenter study to evaluate the diagnostic performance of the dual energy computed tomography perfusion for the detection and exclusion of hemodynamically significant coronary artery disease, as defined by fractional flow reserve, the reference standard. The targeted population is subjects with suspected coronary artery disease who are referred for non-emergent clinically-indicated invasive coronary angiography or rest-stress nuclear imaging. The study is considered non-significant risk as investigators will be blinded to the dual energy computed tomography perfusion analyses will in no part play a role in the subject's medical treatment or clinical course.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Patients provide written informed consent
* Patients scheduled to undergo clinically-indicated non-emergent invasive coronary angiography
* suspected coronary artery disease

Exclusion Criteria:

* Suspicion of acute coronary syndrome (acute myocardial infarction and unstable angina)
* Recent prior myocardial infarction within 40 days of ICA
* Known complex congenital heart disease
* Significant arrhythmia or tachycardia
* Impaired chronic renal function (serum creatinine \> 1.5 mg/dl or GFR \< 30 ml/min)
* Patients with known anaphylactic allergy to iodinated contrast
* Pregnancy or unknown pregnancy status
* Contraindication to adenosine, including 2nd or 3rd degree heart block; sick sinus syndrome; long QT syndrome; severe hypotension, severe asthma, severe COPD or bronchodilator-dependent COPD
* Patient requires an emergent procedure
* Evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure \<90 mmHg, and severe congestive heart failure (NYHA III or IV) or acute pulmonary edema

Primary outcomes:
measure: Diagnostic accuracy of dual energy CCTA plus perfusion (DECTP) to determine presence or absence of at least one hemodynamically (HD)-significant coronary artery stenosis* at the subject-level when compared to FFR.
timeFrame: Within 60 days between CT and cath
Secondary outcomes:
measure: Sensitivity, specificity, positive predictive value, and negative predictive value of coronary computed tomography angiography plus DECTP at the subject level using binary outcomes when compared to fractional flow reserve as the reference standard.
timeFrame: Within 60 days between tests
measure: Diagnostic performance (accuracy, sensitivity, specificity, PPV, and NPV) of CCTA plus DECTP for HD-significant stenosis* at the vessel-level when compared to FFR.
timeFrame: Within 60 days between tests
Other outcomes:
measure: Diagnostic accuracy of DECTP alone for HD-significant stenosis* at the subject-level and vessel-level when compared to FFR.
timeFrame: Within 60 days between tests
measure: Diagnostic accuracy of CCTA plus DECTP for HD-significant stenosis at the subject-level and vessel-level when compared to MPI.
timeFrame: Within 60 days between tests
measure: Diagnostic accuracy of DECTP alone for HD-significant stenosis at the subject-level and vessel-level when compared to MPI.
timeFrame: Within 60 days between tests
Locations:
city: Overland Park
country: United States
facility: Midwest Heart and Vascular Specialists
state: Kansas
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Columbus
country: United States
facility: Wexner Medical Center, The Ohio State University Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: NewYork-Presbyterian Hospital and the Weill Cornell Medical College
name: Leslee J Shaw, PhD
role: PRINCIPAL_INVESTIGATOR
References: