Dan-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease

Coronary Artery Disease Clinical Trial

Official title:

Dan-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02264717
• Other study ID #: Dan-NICAD
• Status: Completed
• Phase: N/A
• First received: September 26, 2014
• Last updated: May 12, 2016
• Start date: September 2014
• Est. completion date: May 2016

Study information

• Verified date: May 2015
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial Summary

1. The primary purpose of this study is to determine the diagnostic accuracy of the CADscore System, a new danish technology that records sounds from turbulence of bloodflow in the coronary vessels.

And secondary:

1. To determine the accuracy of cardiac magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT), as secondary tests after detection of obstructive anatomic coronary artery stenosis by coronary computed tomographic angiography (CCTA).

2. To examine the patient population for bio-genetic markers related to development of arteriosclerosis.

3. To evaluate virtual fractional flow reserve (vFFR) computed from coronary angiograms.

Description:

Primary study CCTA is currently the first choice to rule out coronary artery disease (CAD) in patients with typical or atypical chest pain. 4500 patients are annually examined with CCTA, in the Central Jutland Region of Denmark, and approximately 80% are discharged after ruling out CAD. CCTA is a diagnostic scan that exposes the patients to radiation, therefore a better risk stratification prior to the test is desirable. The CADscore is a newly developed danish technology that has been tested so far in 1000 patients. An area under the curve of the receiver operating characteristic (AUC of ROC) of 75-80 has been determined compared to conventional coronary angiography using quantitative coronary angiography (CCA-QCA). This indicates that the CADscore could potentially be used to diagnose CAD as a supplement or risk stratification prior to CCTA.

We aim to evaluate the CADscore in a large clinical trial including 2000 patients that by clinical indication undergo cCTA. After cCTA approximately 20 % (400 patients) will need evaluation by CCA with FFR. CADscore results will be compared to CCTA and CCA-QCA. Secondary, the CADscore will be compared to the results of CCA-FFR and perfusion scans, Cardiac-MRI and SPECT.

Substudies

1. Perfusion scans

CCTA demonstrates good diagnostic performance for detection and exclusion of anatomic coronary artery stenosis, but several studies have previously shown that CCTA has a low positive predictive value for identification of hemodynamically significant CAD. This emphasizes the need for additional tests to evaluate the severity (or exclusion) of hemodynamically significant CAD. Measurement of FFR during CCA represents the "gold standard" for assessment of the hemodynamic significance of coronary artery stenosis. The disadvantage of CCA with FFR is that it is an invasive procedure.

After cCTA approximately 20 % (400 patients) will need further testing and that group of patients will be randomized to either Cardiac MRI or SPECT followed by CCA with FFR.

The substudy aims to evaluate the diagnostic accuracy of perfusion imaging (Cardiac MRI and SPECT) compared with CCA with FFR.

2. Virtual FFR

The accuracy and precision of virtual-FFR compared with conventional FFR will be determined. Virtual FFR is computed from the coronary angiogram using computational fluid dynamics. Subjects with diameter stenosis in the range of 30 to 90% by visual estimate in one or more vessel segments with reference diameter ≥2.0 mm will be included in the analysis. FFR is the reference standard to determine the presence or absence of hemodynamically significant obstruction with a cut-off value of 0.80. Computation of vFFR with and without hyperaemia will be compared.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1676
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Indication for Cardiac CT

• Signed

Exclusion Criteria:

• Age under 40

• Pregnant, potentially pregnant or breast feeding

• Contraindication for adenosine (severe asthma, clinical aortic stenosis)

• Reduced kidney function (eGFR < 40 ml/min)

• Contraindication for MRI

• Previous history of allergy to contrast

• Previous revascularisation procedure

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Angina Pectoris
• Arteriosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Procedure:
• SPECT
Patients are randomized to either SPECT or Cardiac MRI
• Cardiac MRI
Patients are randomized to either SPECT or Cardiac MR

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus	Region Midtjylland
Denmark	Regional Hospital of Herning	Herning	Region Midtjylland
Denmark	Regional Hospital of Silkeborg	Silkeborg	Region Midtjylland

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Feasibility of virtual FFR	Feasibility of vFFR compared to conventional FFR assessed as fraction of conventional FFR measurements where a vFFR values is computed by the core lab.	one day	No
Other	Diagnostic accuracy of virtual FFR	Diagnostic accuracy of vFFR as the area under the receiver operating characteristic curve (AUC by ROC). The performance of vFFR in predicting functionally significant stenosis is assessed with and without hyperaemia using sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy, together with their 95% confidence intervals.	one day	No
Other	The diagnostic accuracy of perfusion imaging (Cardiac MRI and SPECT)	Diagnostic performance will be evaluated as the AUC-ROC, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy.; CAD is defined as a CCA-FFR below 0,80. A Chi2 test will be used to compare SPECT and Cardiac-MRI.	Within 4 weeks after the CCTA	No
Primary	Diagnostic accuracy of the CADscore system compared to CCTA and CCA-QCA.	Diagnostic precision will be evaluated as the AUC-ROC. The CADscore will be dichotomized at cut off values of 20,25 and 30 and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. The CADscore system operates with 3 intervals of risk stratification: <20, 20-30, >30 (low, intermedia and high risk of cardio vascular disease, respectively) Obstructive CAD is defined as = 50% diameter stenosis as determined by quantitative analysis of CCA (QCA). Non-Obstructive CAD is defined as no detection of obstructive anatomic coronary artery stenosis by CCTA or stenosis detected by CCTA combined with a evaluation by CCA-QCA demonstrating a luminal stenosis diameter < 50 %.	Within one week before or after CCTA	No
Secondary	Safety of CADScore Safety of CADScore	Registration of adverse events related to the use of CADScore	One week after the use of CADScore	Yes
Secondary	Diagnostic accuracy of the CADScore system compared to CCA-FFR.	Diagnostic precision will be evaluated as the AUC-ROC and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy.; CAD is defined as CCA-FFR under 0.80.	Within four weeks after CADScore	No