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Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 (Dan-NICAD 2)

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ClinicalTrials.gov Identifier: NCT03481712
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : January 25, 2019
Sponsor:
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

In a cohort of symptomatic patients referred to coronary computed tomography angiography (CCTA), the investigators aim:

  1. To investigate and compare the diagnostic precision of Rubidium Positron Emission Tomography (Rb PET) and 3 Tesla Cardiac Magnetic Resonance imaging (3T CMRI) in patients where CCTA does not exclude significant coronary artery disease (CAD) using invasive coronary angiography with fractional flow reserve (ICA-FFR) as reference standard.
  2. To evaluate the diagnostic precision of quantitative flow ratio (QFR) and ICA-FFR in patients where CCTA does not exclude significant CAD using Rb PET and 3T CMRI as reference standard.
  3. To show superiority for the CADScor®System compared to the Diamond-Forrester score in detection of CAD with CCTA and ICA quantitative coronary angiography (ICA-QCA) as reference standard.
  4. To study the diagnostic accuracy of computed tomography fractional flow reserve (CT-FFR) in patients where CCTA does not exclude significant CAD with ICA-FFR as reference standard.
  5. To identify and characterize genetic risk variants´ and circulating biomarkers´ importance in developing CAD.
  6. To evaluate the bone mineral density in the hip and spine and correlate this to the degree of vascular calcification.

Condition or disease Intervention/treatment
Angina Pectoris Atherosclerosis Coronary Artery Disease Myocardial Ischemia Diagnostic Test: Diagnostic tests

Detailed Description:

CCTA has become the preferred diagnostic modality for symptomatic patients with low to intermediate risk of CAD. Of the patients examined, CCTA exclude cardiovascular disease in 70-80% with an excellent negative predictive value of more than 95%. Having a low positive predictive value, however, CCTA often overestimates the severity of CAD, especially in patients with moderate to severe coronary calcification. Following CCTA, patients are hence unnecessarily tested using golden standard ICA-FFR. These ICAs often show no obstructive coronary stenosis and are therefore not followed by revascularization. The issues outlined raises the question of whether it is possible (1) to make a more precise risk stratification and consequently better selection of patients prior to CCTA and (2) to reduce the number of patients referred for unnecessary ICAs following CCTA.

In patients with suspicion of coronary stenosis detected by CCTA, current guidelines recommend verification of myocardial ischemia. In Dan-NICAD 2, we intend to investigate the diagnostic accuracy of advanced non-invasive myocardial perfusion imaging tests; Rb PET and 3T CMRI. These examinations have shown a high diagnostic accuracy in symptomatic patients with high risk of ischemic heart disease. However, the diagnostic accuracy is not investigated in patients as follow-up after CCTA.

An alternative way to increase the diagnostic accuracy of CCTA and thus avoid unnecessary downstream testing using ICA is to utilize the ability to extract physiological information from the anatomical CCTA images. CT-FFR has in previous studies shown promising results. CT-FFR has not been head to head compared against Rb PET and 3T CMRI.

Obtained during ICA, QFR is a novel wire-free approach for fast computation of FFR with potential to increase the global use of physiological lesion assessment. QFR is superior to traditional assessment of intermediate coronary lesions (ICA-QCA diameter stenosis). However, disagreement between FFR and QFR has been identified in up to 20% of all measurements.

Acoustic detections of coronary stenosis from automatically recorded and analyzed heart sounds is a newly developed technology potentially useful for pre-test risk stratification before e.g. CCTA. One of these devices, the CADScor®System, has previously shown an area under the receiver operating characteristic curve (AUC of ROC) of 70-80% compared to conventional ICA-QCA. This indicates that the CADScor®System could potentially supplement clinical assessment of CAD and be used for risk stratification prior to CCTA.

The investigators aim to obtain blood samples for biobank purposes and record heart sounds with the CADScor®System in 2000 patients that by clinical evaluation undergo CCTA. In approximately 400 patients (20%), CCTA does not exclude significant CAD. These patients are all examined using Rb PET, 3T CMRI, and ICA with QCA. In patients with a coronary diameter stenosis of 30-90% determined during the ICA examination, FFR, coronary flow reserve (CFR) and QFR is performed.


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Study Type : Observational
Estimated Enrollment : 2000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2
Actual Study Start Date : January 24, 2018
Estimated Primary Completion Date : January 24, 2020
Estimated Study Completion Date : January 24, 2020

Resource links provided by the National Library of Medicine



Intervention Details:
  • Diagnostic Test: Diagnostic tests

    Head-to-head comparison between:

    • CADScor and Diamond-Foster score
    • Rb PET and 3T CMRI
    • QFR and ICA-FFR


Primary Outcome Measures :
  1. Diagnostic accuracy of 3T CMRI vs. Rb PET. [ Time Frame: 4 weeks after inclusion. ]
    Head-to-head comparison using ICA-FFR as reference standard. Diagnostic accuracy is measured using specificity, sensitivity, positive and negative predictive value and likelihood ratios.

  2. Diagnostic accuracy of QFR vs. ICA-FFR. [ Time Frame: 4 weeks after inclusion. ]

    Head-to-head comparison using myocardial perfusion examinations as reference standard.

    Diagnostic accuracy is measured using specificity, sensitivity, positive and negative predictive values, likelihood ratios and area under receiving operating curves (AUC-ROC).


  3. Diagnostic accuracy of CADScor vs. Diamond-Foster Score. [ Time Frame: 4 weeks after inclusion. ]
    AUC-ROC for CAD-score and Diamond-Forrester score in detection of CAD with CCTA and ICA-QCA as reference in patients ≥40 years.


Secondary Outcome Measures :
  1. Genome-wide Associations. [ Time Frame: 4 weeks after inclusion. ]
    The primary analysis will be a genome-wide association analysis, to determine candidate genes and markers underlying coronary artery disease and bone mineralization.

  2. Bone mineral density. [ Time Frame: 1 day after inclusion. ]
    To study the bone mineral density in this cohort and its relation to vascular calcification.

  3. Coronary flow measurement´s impact on diagnostic accuracy of myocardial perfusion imaging (MPI). [ Time Frame: 4 weeks after inclusion. ]
    Impact of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) on myocardial perfusion imaging (MPI) diagnostic accuracy using specificity, sensitivity, positive and negative predictive values.

  4. Diagnostic accuracy of quantitative CMRI analysis. [ Time Frame: 4 weeks after inclusion. ]
    Diagnostic accuracy of quantitative CMRI analysis compared to ICA with FFR-CFR.

  5. Absolute measurements of coronary flow with quantitative CMRI analysis. [ Time Frame: 4 weeks after inclusion. ]
    Correlation analysis between flow measurements estimated by quantitative CMRI vs. Rb PET.

  6. Diagnostic accuracy of CADScor vs. Diamond-Foster Score. [ Time Frame: 4 weeks after inclusion. ]
    AUC-ROCs for CAD-score and Diamond-Forrester score in detection of CAD with CCTA and ICA-QCA as reference in total population.

  7. Diagnostic accuracy of CADScor vs. Diamond-Forrester Score. [ Time Frame: 4 weeks after inclusion. ]
    Sensitivity, specificity, negative and positive predictive value of CAD-score and Diamond-Forrester score with CCTA and ICA-QCA as reference standard.

  8. CADScor. [ Time Frame: 4 weeks after inclusion. ]
    AUC-ROCs, sensitivity, specificity, negative and positive predictive value of CAD-score with ICA-FFR as reference standard.

  9. QFR FFR mismatch. [ Time Frame: 4 weeks after inclusion. ]
    A subgroup analysis is performed for patients with mismatch between QFR and FFR using CFR and IMR as reference standard.

  10. Diagnostic accuracy of CT-FFR. [ Time Frame: 4 weeks after inclusion. ]
    To evaluate the diagnostic accuracy of CT-FFR using ICA-FFR as reference standard.

  11. Effect of revascularisation on symptoms of angina pectoris. [ Time Frame: 3+12 months after ICA ]
    Evaluation of coronary revascularissation to reduce symptoms of angina pectoris 3 and 12 mdr. after ICA.

  12. Prognostic value of clinical, biomarker, and genetic information. [ Time Frame: 3+5+10 years after inclusion. ]
    To validate the 3, 5 and 10 yr. prognostic value of a pre-test probability score including clinical, biomarker and genitic information in patients with symptoms suggestive of CAD referred for coronary CTA.

  13. Prognostic value of heart sound analysis and CAD-score. [ Time Frame: 3+5+10 years after inclusion. ]
    To investigate the 3, 5 and 10 yr. prognostic value of pre-specified heart sound analysis and CAD-score in patients with symptoms suggestive of CAD referred for coronary CTA.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with an indication for CCTA.
Criteria

Inclusion Criteria:

  • Patients with an indication for CCTA.
  • Qualified patients who have signed a written informed consent form.

Exclusion Criteria:

CADScor specific

  • Fragile or compromised skin in the area for application of the CADScor®Patch.
  • Known allergy to polyacrylate adhesives.
  • Significant operation scars or abnormal body shape in left IC4 (4th Inter Costal region).
  • Use of vasodilating agents at the same day and prior to CAD-score measurements.

Demography and co-existing cardiac morbidity specific

  • Age below 30 years.
  • Patients having a donor heart, a mechanic heart, or mechanical heart pump.
  • Suspicion acute coronary syndrome Previous revascularization.

Scan specific

CCTA:

  • Pregnant women, including women who are potentially pregnant or lactating.
  • Reduced kidney function, with an estimated glomerular filtration rate (eGFR) < 40 mL/min.
  • Allergy to X-ray contrast medium.

CMRI and PET:

  • Contra-indication for adenosine (severe asthma, advanced AV block, or critical aorta stenosis).
  • Contra-indications for MRI (implanted medicinal pumps or nerve stimulators, magnetic foreign objects in sensitive areas, i.e. the eye).
  • Patients having an ICD or pacemaker, a cochlea implant, or metal clips evaluated by the including doctor.

General:

- Patients not able to breath-hold (COPD/asthma).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03481712


Contacts
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Contact: Morten Böttcher, MD, Ph.D 25775134 morboett@rm.dk

Locations
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Denmark
Aarhus University Hospital Recruiting
Aarhus, Region Midtjylland, Denmark, 8200
Contact: Hans E Bøtker, MD, Ph.D, Professor         
Regional Hospital of Herning Recruiting
Herning, Region Midtjylland, Denmark, 7400
Contact: Morten Böttcher, MD, Ph.D         
Regional Hospital of Silkeborg Recruiting
Silkeborg, Region Midtjylland, Denmark, 8600
Contact: Lars Frost, MD, Ph.D         
Sponsors and Collaborators
University of Aarhus
Investigators
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Principal Investigator: Morten Böttcher, MD, Ph.D Regional Hospital of Herning, department of cardiology

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Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT03481712     History of Changes
Other Study ID Numbers: 000-0001
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Ischemia
Atherosclerosis
Angina Pectoris
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms