NCT02264717

Brief Summary

1\. The primary purpose of this study is to determine the diagnostic accuracy of the CADscore System, a new danish technology that records sounds from turbulence of bloodflow in the coronary vessels. And secondary:

  1. 1.To determine the accuracy of cardiac magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT), as secondary tests after detection of obstructive anatomic coronary artery stenosis by coronary computed tomographic angiography (CCTA).
  2. 2.To examine the patient population for bio-genetic markers related to development of arteriosclerosis.
  3. 3.To evaluate virtual fractional flow reserve (vFFR) computed from coronary angiograms.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,676

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2014

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2014

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

September 26, 2014

Completed
19 days until next milestone

First Posted

Study publicly available on registry

October 15, 2014

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2016

Completed
Last Updated

May 13, 2016

Status Verified

May 1, 2015

Enrollment Period

1.7 years

First QC Date

September 26, 2014

Last Update Submit

May 12, 2016

Conditions

Angina PectorisArteriosclerosisCoronary Artery DiseaseMyocardial Ischemia

Outcome Measures

Primary Outcomes (1)

  • Diagnostic accuracy of the CADscore system compared to CCTA and CCA-QCA.

    Diagnostic precision will be evaluated as the AUC-ROC. The CADscore will be dichotomized at cut off values of 20,25 and 30 and performance reported with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. The CADscore system operates with 3 intervals of risk stratification: \<20, 20-30, \>30 (low, intermedia and high risk of cardio vascular disease, respectively) Obstructive CAD is defined as ≥ 50% diameter stenosis as determined by quantitative analysis of CCA (QCA). Non-Obstructive CAD is defined as no detection of obstructive anatomic coronary artery stenosis by CCTA or stenosis detected by CCTA combined with a evaluation by CCA-QCA demonstrating a luminal stenosis diameter \< 50 %.

    Within one week before or after CCTA

Secondary Outcomes (2)

  • Safety of CADScore Safety of CADScore

    One week after the use of CADScore

  • Diagnostic accuracy of the CADScore system compared to CCA-FFR.

    Within four weeks after CADScore

Other Outcomes (3)

  • Feasibility of virtual FFR

    one day

  • Diagnostic accuracy of virtual FFR

    one day

  • The diagnostic accuracy of perfusion imaging (Cardiac MRI and SPECT)

    Within 4 weeks after the CCTA

Study Arms (2)

Cardiac MRi

ACTIVE COMPARATOR

A minimum of 150 patients will be randomized to Cardiac MRI followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA)

Procedure: Cardiac MRI

SPECT

ACTIVE COMPARATOR

A minimum 150 patients will be randomized to SPECT followed by conventional angiography CCA-FFR, after detection of obstructive anatomic coronary artery stenoses on coronary Computed Tomography Angiography (cCTA).

Procedure: SPECT

Interventions

SPECTPROCEDURE

Patients are randomized to either SPECT or Cardiac MRI

SPECT
Cardiac MRIPROCEDURE

Patients are randomized to either SPECT or Cardiac MR

Cardiac MRi

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Indication for Cardiac CT
  • Signed

You may not qualify if:

  • Age under 40
  • Pregnant, potentially pregnant or breast feeding
  • Contraindication for adenosine (severe asthma, clinical aortic stenosis)
  • Reduced kidney function (eGFR \< 40 ml/min)
  • Contraindication for MRI
  • Previous history of allergy to contrast
  • Previous revascularisation procedure

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

Location

Regional Hospital of Herning

Herning, Central Jutland, 7400, Denmark

Location

Regional Hospital of Silkeborg

Silkeborg, Central Jutland, 8600, Denmark

Location

Related Publications (15)

  • 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: 40887988DERIVED

  • 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: 40590244DERIVED

  • 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: 39788470DERIVED

  • Pedersen G, Dahl JN, Rasmussen LD, Garm Blavnsfeldt AB, Bottcher SH, Bottcher MH, Nyegaard M, Nissen L, Winther S. Biomarkers for identification of high-risk coronary artery plaques in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2024 Sep-Oct;18(5):467-475. doi: 10.1016/j.jcct.2024.06.009. Epub 2024 Jul 2.

    PMID: 38955554DERIVED

  • Moller PL, Rohde PD, Dahl JN, Rasmussen LD, Nissen L, Schmidt SE, McGilligan V, Gudbjartsson DF, Stefansson K, Holm H, Bentzon JF, Bottcher M, Winther S, Nyegaard M. Predicting the presence of coronary plaques featuring high-risk characteristics using polygenic risk scores and targeted proteomics in patients with suspected coronary artery disease. Genome Med. 2024 Mar 20;16(1):40. doi: 10.1186/s13073-024-01313-8.

    PMID: 38509622DERIVED

  • Moller PL, Rohde PD, Dahl JN, Rasmussen LD, Schmidt SE, Nissen L, McGilligan V, Bentzon JF, Gudbjartsson DF, Stefansson K, Holm H, Winther S, Bottcher M, Nyegaard M. Combining Polygenic and Proteomic Risk Scores With Clinical Risk Factors to Improve Performance for Diagnosing Absence of Coronary Artery Disease in Patients With de novo Chest Pain. Circ Genom Precis Med. 2023 Oct;16(5):442-451. doi: 10.1161/CIRCGEN.123.004053. Epub 2023 Sep 27.

    PMID: 37753640DERIVED

  • Westra J, Rasmussen LD, Eftekhari A, Winther S, Karim SR, Johansen JK, Hammid O, Sondergaard HM, Ejlersen JA, Gormsen LC, Mogensen LJH, Bottcher M, Holm NR, Christiansen EH. Coronary Artery Stenosis Evaluation by Angiography-Derived FFR: Validation by Positron Emission Tomography and Invasive Thermodilution. JACC Cardiovasc Imaging. 2023 Oct;16(10):1321-1331. doi: 10.1016/j.jcmg.2023.02.008. Epub 2023 Apr 12.

    PMID: 37052562DERIVED

  • Winther S, Nissen L, Schmidt SE, Westra J, Andersen IT, Nyegaard M, Madsen LH, Knudsen LL, Urbonaviciene G, Larsen BS, Struijk JJ, Frost L, Holm NR, Christiansen EH, Botker HE, Bottcher M. Advanced heart sound analysis as a new prognostic marker in stable coronary artery disease. Eur Heart J Digit Health. 2021 Mar 19;2(2):279-289. doi: 10.1093/ehjdh/ztab031. eCollection 2021 Jun.

    PMID: 36712398DERIVED

  • Christiansen MK, Winther S, Nissen L, Vilhjalmsson BJ, Frost L, Johansen JK, Moller PL, Schmidt SE, Westra J, Holm NR, Jensen HK, Christiansen EH, Guethbjartsson DF, Holm H, Stefansson K, Botker HE, Bottcher M, Nyegaard M. Polygenic Risk Score-Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain. Circ Genom Precis Med. 2021 Jun;14(3):e003298. doi: 10.1161/CIRCGEN.120.003298. Epub 2021 May 25.

    PMID: 34032468DERIVED

  • Therkildsen J, Nissen L, Jorgensen HS, Thygesen J, Ivarsen P, Frost L, Isaksen C, Langdahl BL, Hauge EM, Boettcher M, Winther S. Thoracic Bone Mineral Density Derived from Cardiac CT Is Associated with Greater Fracture Rate. Radiology. 2020 Sep;296(3):499-508. doi: 10.1148/radiol.2020192706. Epub 2020 Jul 14.

    PMID: 32662758DERIVED

  • Christiansen MK, Nissen L, Winther S, Moller PL, Frost L, Johansen JK, Jensen HK, Guethbjartsson D, Holm H, Stefansson K, Botker HE, Bottcher M, Nyegaard M. Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden. J Am Heart Assoc. 2020 Feb 4;9(3):e014795. doi: 10.1161/JAHA.119.014795. Epub 2020 Jan 25.

    PMID: 31983321DERIVED

  • Winther S, Nissen L, Westra J, Schmidt SE, Bouteldja N, Knudsen LL, Madsen LH, Frost L, Urbonaviciene G, Holm NR, Christiansen EH, Botker HE, Bottcher M. Pre-test probability prediction in patients with a low to intermediate probability of coronary artery disease: a prospective study with a fractional flow reserve endpoint. Eur Heart J Cardiovasc Imaging. 2019 Nov 1;20(11):1208-1218. doi: 10.1093/ehjci/jez058.

    PMID: 31083725DERIVED

  • Westra J, Tu S, Winther S, Nissen L, Vestergaard MB, Andersen BK, Holck EN, Fox Maule C, Johansen JK, Andreasen LN, Simonsen JK, Zhang Y, Kristensen SD, Maeng M, Kaltoft A, Terkelsen CJ, Krusell LR, Jakobsen L, Reiber JHC, Lassen JF, Bottcher M, Botker HE, Christiansen EH, Holm NR. Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II). Circ Cardiovasc Imaging. 2018 Mar;11(3):e007107. doi: 10.1161/CIRCIMAGING.117.007107.

    PMID: 29555835DERIVED

  • Winther S, Nissen L, Schmidt SE, Westra JS, Rasmussen LD, Knudsen LL, Madsen LH, Kirk Johansen J, Larsen BS, Struijk JJ, Frost L, Holm NR, Christiansen EH, Botker HE, Bottcher M. Diagnostic performance of an acoustic-based system for coronary artery disease risk stratification. Heart. 2018 Jun;104(11):928-935. doi: 10.1136/heartjnl-2017-311944. Epub 2017 Nov 9.

    PMID: 29122932DERIVED

  • 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: 27225018DERIVED

MeSH Terms

Conditions

Angina PectorisArteriosclerosisCoronary Artery DiseaseMyocardial Ischemia

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesVascular DiseasesChest PainPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsArterial Occlusive DiseasesCoronary Disease

Study Officials

  • Morten Bøttcher, MD, Ph.D

    Regional Hospital of Herning, department of cardiology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2014

First Posted

October 15, 2014

Study Start

September 1, 2014

Primary Completion

May 1, 2016

Study Completion

May 1, 2016

Last Updated

May 13, 2016

Record last verified: 2015-05

Data Sharing

IPD Sharing
Will not share

Locations

DK(3)