Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 3

NCT ID: NCT04707859

Last Updated: 2021-01-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-01-05

Study Completion Date

2023-01-05

Brief Summary

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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.

Detailed Description

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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. Dan-NICAD 3 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 ICA-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 microcirculatiory function is under development and this study will validated these algorithms. Furthermore, the prognostic value of CT-FFR is unknown and will be tested in the pooled cohort of Dan-NICAD 1, 2 and 3.

Obtained during ICA, quantitative flow ratio (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 based on quantitative coronary analysis of ICA. However, disagreement between ICA-FFR and QFR has been identified in up to 20% of all measurements. QFR will be validated compared to PET and ICA-FFR.

Conditions

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Angina Pectoris Atherosclerosis Coronary Artery Disease Myocardial Ischemia

Keywords

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Positron Emission Tomography Coronary Computed Tomography Angiography Rubidium 15O water Fractional flow reserve

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort

Participants consenting to the study will undergo:

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

Patients with suspicion of coronary stenosis detected by CCTA will after 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)

Head to head comparison: Rubidium vs 15O-water PET

Intervention Type DIAGNOSTIC_TEST

Head to head comparison with invasive FFR as reference. Adjustment for abnormal microcirculation

Interventions

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Head to head comparison: Rubidium vs 15O-water PET

Head to head comparison with invasive FFR as reference. Adjustment for abnormal microcirculation

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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 or 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 or allergy to X-ray contrast medium.

PET: contra-indication for adenosine (severe asthma, advanced atrioventricular block, or critical aorta stenosis).
Minimum Eligible Age

30 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Simon Winther, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Unit West, Herning, Denmark

Locations

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Gødstrup Hospital

Herning, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Simon Winther, MD, PhD

Role: CONTACT

Phone: 78430000

Email: [email protected]

Facility Contacts

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Simon Winther, MD, PhD

Role: primary

References

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Nissen L, Winther S, Isaksen C, Ejlersen JA, Brix L, Urbonaviciene G, Frost L, Madsen LH, Knudsen LL, Schmidt SE, Holm NR, Maeng M, Nyegaard M, Botker HE, Bottcher M. Danish study of Non-Invasive testing in Coronary Artery Disease (Dan-NICAD): study protocol for a randomised controlled trial. Trials. 2016 May 26;17(1):262. doi: 10.1186/s13063-016-1388-z.

Reference Type BACKGROUND
PMID: 27225018 (View on PubMed)

Rasmussen LD, Winther S, Westra J, Isaksen C, Ejlersen JA, Brix L, Kirk J, Urbonaviciene G, Sondergaard HM, Hammid O, Schmidt SE, Knudsen LL, Madsen LH, Frost L, Petersen SE, Gormsen LC, Christiansen EH, Eftekhari A, Holm NR, Nyegaard M, Chiribiri A, Botker HE, Bottcher M. Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): Study design for a controlled study of diagnostic accuracy. Am Heart J. 2019 Sep;215:114-128. doi: 10.1016/j.ahj.2019.03.016. Epub 2019 May 1.

Reference Type BACKGROUND
PMID: 31323454 (View on PubMed)

Westra J, Rasmussen LD, Karim SR, Jensen RV, Ejlersen JA, Gormsen LC, Bottcher M, Eftekhari A, Winther S, Christiansen EH. Coronary microvascular disease in patients referred to coronary angiography following coronary computed tomography angiography. EuroIntervention. 2025 Sep 1;21(17):e1005-e1014. doi: 10.4244/EIJ-D-24-01155.

Reference Type DERIVED
PMID: 40887988 (View on PubMed)

Rasmussen LD, Sikjaer M, Soby JH, Pedersen OB, Westra J, Efthekhari A, Christiansen EH, Foldyna B, Williams MC, Dweck MR, Newby DE, Douglas PS, Bottcher M, Winther S. Dual probability approach for risk adjustment in patients with a low clinical likelihood of coronary artery disease. Eur Heart J Cardiovasc Imaging. 2025 Aug 29;26(9):1507-1517. doi: 10.1093/ehjci/jeaf193.

Reference Type DERIVED
PMID: 40590244 (View on PubMed)

Winther S, Rasmussen LD, Karim SR, Westra J, Dahl JN, Soby JH, Nissen L, Lomstein FB, Wurtz M, Sundboll JM, Ejlersen JA, Mortensen J, Tolbod LP, Sondergaard HM, Hansson NCL, Nyegaard M, Jensen RV, Madsen MA, Christiansen EH, Gormsen LC, Bottcher M. Myocardial Perfusion Imaging With PET: A Head-to-Head Comparison of 82Rubidium Versus 15O-water Tracers Using Invasive Coronary Measurements as Reference. Circ Cardiovasc Imaging. 2025 Jun;18(6):e017479. doi: 10.1161/CIRCIMAGING.124.017479. Epub 2025 Apr 3.

Reference Type DERIVED
PMID: 40177753 (View on PubMed)

Brix GS, Rasmussen LD, Rohde PD, Nissen L, Nyegaard M, O'Donoghue ML, Bottcher M, Winther S. Elevated lipoprotein(a) levels are independently associated with the presence of significant coronary stenosis in de-novo patients with stable chest pain. Am Heart J. 2025 Apr;282:103-113. doi: 10.1016/j.ahj.2025.01.001. Epub 2025 Jan 7.

Reference Type DERIVED
PMID: 39788470 (View on PubMed)

Rasmussen LD, Westra J, Karim SR, Dahl JN, Soby JH, Ejlersen JA, Gormsen LC, Eftekhari A, Christiansen EH, Bottcher M, Winther S. Microvascular resistance reserve: impact on health status and myocardial perfusion after revascularization in chronic coronary syndrome. Eur Heart J. 2025 Feb 3;46(5):424-435. doi: 10.1093/eurheartj/ehae604.

Reference Type DERIVED
PMID: 39217607 (View on PubMed)

Rasmussen LD, Karim SR, Westra J, Nissen L, Dahl JN, Brix GS, Knuuti J, Schmidt SE, Holm NR, Christiansen EH, Eftekhari A, Bottcher M, Winther S. Clinical Likelihood Prediction of Hemodynamically Obstructive Coronary Artery Disease in Patients With Stable Chest Pain. JACC Cardiovasc Imaging. 2024 Oct;17(10):1199-1210. doi: 10.1016/j.jcmg.2024.04.015. Epub 2024 Jul 3.

Reference Type DERIVED
PMID: 38970593 (View on PubMed)

Winther S, Dupont Rasmussen L, Westra J, Abdulzahra SRK, Dahl JN, Gormsen LC, Christiansen EH, Brix GS, Mortensen J, Ejlersen JA, Sondergaard HM, Hansson NCL, Holm NR, Knudsen LL, Eftekhari A, Moller PL, Rohde PD, Nyegaard M, Bottcher M. Danish study of Non-Invasive Testing in Coronary Artery Disease 3 (Dan-NICAD 3): study design of a controlled study on optimal diagnostic strategy. Open Heart. 2023 Jul;10(2):e002328. doi: 10.1136/openhrt-2023-002328.

Reference Type DERIVED
PMID: 37487656 (View on PubMed)

Other Identifiers

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Dan-NICAD 3

Identifier Type: -

Identifier Source: org_study_id