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

May 12, 2016 updated by: University of Aarhus

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

1676

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Region Midtjylland
      • Aarhus, Region Midtjylland, Denmark, 8200
        • Aarhus University Hospital
      • Herning, Region Midtjylland, Denmark, 7400
        • Regional Hospital of Herning
      • Silkeborg, Region Midtjylland, Denmark, 8600
        • Regional Hospital of Silkeborg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cardiac MRi
A minimum of 150 patients will be randomized to Cardiac MRI followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA)
Procedure: Cardiac MRI
Patients are randomized to either SPECT or Cardiac MR
Active Comparator: SPECT
A minimum 150 patients will be randomized to SPECT followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA).
Procedure: SPECT
Patients are randomized to either SPECT or Cardiac MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of the CADscore system compared to CCTA and CCA-QCA.
Time Frame: Within one week before or after CCTA
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of CADScore Safety of CADScore
Time Frame: One week after the use of CADScore
Registration of adverse events related to the use of CADScore
One week after the use of CADScore
Diagnostic accuracy of the CADScore system compared to CCA-FFR.
Time Frame: Within four weeks after CADScore

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of virtual FFR
Time Frame: one day
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
Diagnostic accuracy of virtual FFR
Time Frame: one day
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
The diagnostic accuracy of perfusion imaging (Cardiac MRI and SPECT)
Time Frame: Within 4 weeks after the CCTA

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Principal Investigator: Morten Bøttcher, MD, Ph.D, Regional Hospital of Herning, department of cardiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

September 26, 2014

First Submitted That Met QC Criteria

October 9, 2014

First Posted (Estimate)

October 15, 2014

Study Record Updates

Last Update Posted (Estimate)

May 13, 2016

Last Update Submitted That Met QC Criteria

May 12, 2016

Last Verified

May 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Dan-NICAD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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