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

NCT04707859 | Unknown

• 1 other identifier: Dan-NICAD 3
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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

1. 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. 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. 3.To validated a pre-test probability model including genetic and circulating biomarkers.
4. 4.To identify and characterize genetic risk variants and circulating biomarkers importance in developing CAD.
5. 5.To evaluate the bone mineral density in the hip and spine and correlate this to the degree of vascular calcification.

Conditions

Angina Pectoris; Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Diagnostic accuracy of Rb PET and 15-O PET

  Head-to-head comparison using ICA-FFR as reference standard stratified for CFR

  ICA: 4 weeks after inclusion

Secondary Outcomes (8)

• Diagnostic accuracy of QFR vs. ICA-FFR

  ICA: 4 weeks after inclusion

• Pre-test probability model of CAD

  ICA: 4 weeks after inclusion

• Diagnostic accuracy of QFR

  ICA: 4 weeks after inclusion

• Diagnostic accuracy of CT-FFR

  ICA: 4 weeks after inclusion

• Effect of reduced myocardial perfusion defect on symptoms of angina pectoris

  Re-PET: 12 months after inclusion

Study Arms (1)

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)

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

Interventions

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

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

Cohort

Eligibility Criteria

• Age: 30 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with an indication for CCTA.

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Gødstrup Hospital

Herning, 7400, Denmark

RECRUITING

Related Publications (9)

• 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.

  PMID: 27225018 BACKGROUND

• 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.

  PMID: 31323454 BACKGROUND

• 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.

  PMID: 40887988 DERIVED

• 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.

  PMID: 40590244 DERIVED

• 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.

  PMID: 40177753 DERIVED

• 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.

  PMID: 39788470 DERIVED

• 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.

  PMID: 39217607 DERIVED

• 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.

  PMID: 38970593 DERIVED

• 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.

  PMID: 37487656 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

From all participants consenting to the study, blood samples are drawn prior to CCTA contrast administration. Samples are centrifuged and processed into etylen-diamin-tetra-eddikesyre (EDTA) and heparin treated 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.

MeSH Terms

Conditions

Angina Pectoris; Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease

Study Officials

• Simon Winther, MD, PhD

  Hospital Unit West, Herning, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simon Winther, MD, PhD

CONTACT

78430000; simwin@rm.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 13, 2021
• Study Start: January 5, 2021
• Primary Completion: July 5, 2022
• Study Completion: January 5, 2023
• Last Updated: January 29, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)