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Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 3 (Dan-NICAD 3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04707859
Recruitment Status : Recruiting
First Posted : January 13, 2021
Last Update Posted : January 13, 2021
Sponsor:
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

Brief Summary:

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

  1. To investigate and compare the diagnostic precision of Rubidium Positron Emission Tomography (Rb PET) and 15O-water PET (15O-water PET) in patients where CCTA does not exclude obstructive coronary artery disease (CAD) using invasive coronary angiography with fractional flow reserve (ICA-FFR) as reference standard.
  2. To study the diagnostic accuracy and prognostic value of computed tomography fractional flow reserve (CT-FFR) in patients where CCTA does not exclude obstructive CAD with ICA-FFR as reference standard.
  3. To validated a pre-test probability model including genetic and circulating biomarkers.
  4. To identify and characterize genetic risk variants´ and circulating biomarkers importance in developing CAD.
  5. 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: Head to head comparison: Rubidium vs 15O-water PET

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 3, we intend to investigate the diagnostic accuracy of advanced non-invasive myocardial perfusion imaging tests; Rb PET and 15O-water PET. 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. In addition, microcirculation may impact the correlation between PET and FFR which this study will investigate further.

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. In addition, calculated estimation of microcirculation is under development and this study will validated these algorithm. Furthermore, to validated the prognostic value of CT-FFR in a pooled analysis including Dan-NICAD 1, 2 and 3.

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.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 3
Actual Study Start Date : January 5, 2021
Estimated Primary Completion Date : July 5, 2022
Estimated Study Completion Date : January 5, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Rubidium

Group/Cohort Intervention/treatment
Cohort

Participants consenting to the study will undergo:

a1) An interview a2) Blood samples withdrawals a3) ECG a4) Non-enhanced CT a5) Coronary CTA a6) Follow-up for > 10 years

Patients with suspicion of coronary stenosis detected by CCTA will after the coroanry CTA undergo:

b1) Rb PET b2) 15O-water PET b3) Invasive coronary angiography with 3 vessel measurement of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR)

Diagnostic Test: Head to head comparison: Rubidium vs 15O-water PET
Head to head comparison with invasive FFR as reference. Adjustment for abnormal microcirculation




Primary Outcome Measures :
  1. Diagnostic accuracy of Rb PET and 15-O PET [ Time Frame: ICA: 4 weeks after inclusion ]
    Head-to-head comparison using ICA-FFR as reference standard stratified for CFR


Secondary Outcome Measures :
  1. Diagnostic accuracy of QFR vs. ICA-FFR [ Time Frame: ICA: 4 weeks after inclusion ]
    Head-to-head comparison using ICA-FFR as reference standard

  2. Pre-test probability model of CAD [ Time Frame: ICA: 4 weeks after inclusion ]
    Advanced pre-test probability model of CAD included clinical information, genetic and circulating biomarkers

  3. Diagnostic accuracy of QFR [ Time Frame: ICA: 4 weeks after inclusion ]
    Head-to-head comparison using ICA-FFR as reference standard

  4. Diagnostic accuracy of CT-FFR [ Time Frame: ICA: 4 weeks after inclusion ]
    Head-to-head comparison with PET using ICA-FFR as reference standard

  5. Effect of reduced myocardial perfusion defect on symptoms of angina pectoris [ Time Frame: Re-PET: 12 months after inclusion ]
    12 months re-PET investigation will by used for estimation of reduction of myocardial perfusion defect size which will be correlated with symptoms of angina pectoris 3 and 12 mdr. after ICA

  6. Prognostic value of clinical, biomarker, genetic information [ Time Frame: Follow-up: 3+5+10 years after inclusion ]
  7. Prognostic value of coronary CTA, Rb PET, 15O-water PET, CT-FFR and QFR [ Time Frame: Follow-up: 3+5+10 years after inclusion ]

Biospecimen Retention:   Samples With DNA
From all participants consenting to the study, blood samples are drawn prior to coronary CTA contrast administration. Samples are centrifuged and processed into EDTA plasma, heparin plasma, and serum, which are aliquoted into individual matrix tubes and placed at -20°C. In addition, one blood samples are placed directly in the freezer for later extraction of genomic DNA.


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-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:

  • 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.

  • 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.

PET:

Contra-indication for adenosine (severe asthma, advanced AV block, or critical aorta stenosis).


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): NCT04707859


Contacts
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Contact: Simon Winther, MD, PhD 78430000 simwin@rm.dk

Locations
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Denmark
Gødstrup Hospital Recruiting
Herning, Denmark, 7400
Contact: Simon Winther, MD, PhD       simwin@rm.dk   
Sponsors and Collaborators
University of Aarhus
Investigators
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Principal Investigator: Simon Winther, MD, PhD Hospital Unit West, Herning, Denmark
Publications:
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Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT04707859    
Other Study ID Numbers: Dan-NICAD 3
First Posted: January 13, 2021    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
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
Keywords provided by University of Aarhus:
Positron Emission Tomography
Coronary Computed Tomography Angiography
Rubidium
15O water
Fractional flow reserve
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Atherosclerosis
Angina Pectoris
Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Chest Pain
Pain
Neurologic Manifestations