Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 3 (Dan-NICAD 3)
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|ClinicalTrials.gov Identifier: NCT04707859|
Recruitment Status : Recruiting
First Posted : January 13, 2021
Last Update Posted : January 13, 2021
In a cohort of symptomatic patients referred to coronary computed tomography angiography (CCTA), the investigators aim is:
- 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.
- 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.
- To validated a pre-test probability model including genetic and circulating biomarkers.
- To identify and characterize genetic risk variants´ and circulating biomarkers importance in developing CAD.
- 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|
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.
|Study Type :||Observational|
|Estimated Enrollment :||1000 participants|
|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|
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
- 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
- Diagnostic accuracy of QFR vs. ICA-FFR [ Time Frame: ICA: 4 weeks after inclusion ]Head-to-head comparison using ICA-FFR as reference standard
- 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
- Diagnostic accuracy of QFR [ Time Frame: ICA: 4 weeks after inclusion ]Head-to-head comparison using ICA-FFR as reference standard
- Diagnostic accuracy of CT-FFR [ Time Frame: ICA: 4 weeks after inclusion ]Head-to-head comparison with PET using ICA-FFR as reference standard
- 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
- Prognostic value of clinical, biomarker, genetic information [ Time Frame: Follow-up: 3+5+10 years after inclusion ]
- 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
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
|Contact: Simon Winther, MD, PhDemail@example.com|
|Herning, Denmark, 7400|
|Contact: Simon Winther, MD, PhD firstname.lastname@example.org|
|Principal Investigator:||Simon Winther, MD, PhD||Hospital Unit West, Herning, Denmark|