Personalized Evaluation of Susptected Myocardial Ischemia

NCT06708000 | Enrolling By Invitation Phase 3

• 1 other identifier: 1-10-72-47-24
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to assess whether the use of clinical risk models, known as Clinical Likelihood (CL) models, can reduce the need for diagnostic examinations without negatively impacting quality of life or prognosis after 12 months in patients with stable new onset chest pain. Additionally, the project will evaluate a newly developed method called Laser Speckle Contrast Imaging for measuring function and oxygen content in the smallest blood vessels (microvasculature) of the hand, which may also reflect blood flow and oxygen content in the microvasculature of the heart.

Conditions

Arteriosclerosis; Coronary Artery Disease; Myocardial Ischemia; Chronic Coronary Syndrome; Angina Pectoris

Keywords

Chronic Coronary Syndrome; Angina Pectoris; Coronary Artery Disease; Clinical Likelihood; Myocardial Ischemia; PERMI

Outcome Measures

Primary Outcomes (1)

• Proportion of Asymptomatic Patients 6 Months After Inclusion

  Resolution 6 months after inclusion, as assessed by SAQ Angina Frequency score of 100%, indicating the absence of angina-related symptoms. This measure will assess the effectiveness of a diagnostic strategy based on Clinical Likelihood (CL) models compared to the standard approach for evaluating patients suspected of stable ischemic heart disease (IHD).

  From enrollment to 6 months after patient inclusion

Secondary Outcomes (6)

• Sensitivity and Specificity for Detecting Obstructive Coronary Artery Disease (CAD)

  From enrollment to 12 months after patient inclusion.

• Proportion of Patients Undergoing Cardiac CT Imaging

  From enrollment to 12 months after patient inclusion

• Seattle Angina Questionnaire (SAQ) Scores for Quality of Life

  3, 6, and 12 months after enrollment

• Dyspnea Assessment: Rose Dyspnea Score for Symptom Evaluation

  3, 6 and 12 months after enrollment

• Correlation Between Peripheral and Cardiac Microvascular Function via LSCI

  At baseline and 6 months after enrollement

Other Outcomes (14)

• Proportion of Patients with Very Low RF-CL and Very Low CACS-CL

  Baseline

• Further Diagnostic Testing for Angina Pectoris and Dyspnea

  3, 6, and 12 months after enrollment

• Proportion of Normal Cardiac CT Scans

  Baseline

Study Arms (2)

Clinical Likelihood-Based Diagnostic Strategy

EXPERIMENTAL

Patients in this arm will be assessed using the Clinical Likelihood (CL) models, including the Risk Factor-Weighted Clinical Likelihood (RF-CL) and Coronary Artery Calcium Score-Weighted Clinical Likelihood (CACS-CL) models.

Diagnostic Test: Clinical Likelihood (CL) Model-Based Diagnostic Strategy

Standard of Care

ACTIVE COMPARATOR

Patients in this arm will follow the standard diagnostic pathway.

Diagnostic Test: Standard of care treatment

Interventions

Clinical Likelihood (CL) Model-Based Diagnostic Strategy DIAGNOSTIC_TEST

The Clinical Likelihood (CL) model-based diagnostic strategy utilizes two models: the RF-CL model and the CACS-CL model. These models assess the pre-test probability of obstructive coronary artery disease (CAD) based on patient factors such as age, sex, symptoms, and traditional cardiovascular risk factors like smoking, diabetes, and hypertension. The CACS-CL model incorporates coronary artery calcium scoring to further refine the risk assessment. Patients identified with a low likelihood of CAD may avoid unnecessary diagnostic testing, such as cardiac CT, while maintaining diagnostic accuracy and safety. This approach aims to optimize resource use, reduce patient burden, and focus on other potential causes of symptoms when CAD is unlikely.

Clinical Likelihood-Based Diagnostic Strategy

Standard of care treatment DIAGNOSTIC_TEST

Patients will follow the standard diagnostic pathway, which includes the use of cardiac CT and other advanced diagnostic procedures based on clinical guidelines. This approach is the current standard of care for patients with suspected obstructive coronary artery disease (CAD). The control group allows for comparison of outcomes with those in the intervention arm, particularly in terms of resource utilization, patient safety, and diagnostic accuracy.

Standard of Care

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with de novo chest pain referred on suspicion of stable ischemic CAD
• Patients capable of providing written informed consent

You may not qualify if:

• Age \<30 years or \>75 years
• Known ischemic heart disease, including previous PCI (with or without stent) and bypass surgery
• Unstable angina pectoris at initial consultation
• Severe COPD or asthma
• Severe valvular disease
• Absolute or relative contraindications for Cardiac CT:
• allergy to iomeron
• pregnant women, including women who are potentially pregnant or lactating
• reduced kidney function with an estimated glomerular filtration rate \<40 ml/min
• LVEF \<45%

Sponsors & Collaborators

• Gødstrup Hospital: lead

Study Sites (1)

Regional Hospital of Godstrup

Herning, 7400, Denmark

Location

Related Publications (5)

• Winther S, Schmidt SE, Mayrhofer T, Botker HE, Hoffmann U, Douglas PS, Wijns W, Bax J, Nissen L, Lynggaard V, Christiansen JJ, Saraste A, Bottcher M, Knuuti J. Incorporating Coronary Calcification Into Pre-Test Assessment of the Likelihood of Coronary Artery Disease. J Am Coll Cardiol. 2020 Nov 24;76(21):2421-2432. doi: 10.1016/j.jacc.2020.09.585.

  PMID: 33213720 BACKGROUND

• Brix GS, Rasmussen LD, Rohde PD, Schmidt SE, Nyegaard M, Douglas PS, Newby DE, Williams MC, Foldyna B, Knuuti J, Bottcher M, Winther S. Calcium Scoring Improves Clinical Management in Patients With Low Clinical Likelihood of Coronary Artery Disease. JACC Cardiovasc Imaging. 2024 Jun;17(6):625-639. doi: 10.1016/j.jcmg.2023.11.008. Epub 2024 Jan 3.

  PMID: 38180413 BACKGROUND

• Rasmussen LD, Fordyce CB, Nissen L, Hill CL Jr, Alhanti B, Hoffmann U, Udelson J, Bottcher M, Douglas PS, Winther S. The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD. JACC Cardiovasc Imaging. 2022 Aug;15(8):1442-1454. doi: 10.1016/j.jcmg.2022.03.009. Epub 2022 May 11.

  PMID: 35926903 BACKGROUND

• Rasmussen LD, Williams MC, Newby DE, Dahl JN, Schmidt SE, Bottcher M, Winther S. External validation of novel clinical likelihood models to predict obstructive coronary artery disease and prognosis. Open Heart. 2023 Dec 6;10(2):e002457. doi: 10.1136/openhrt-2023-002457.

  PMID: 38056915 BACKGROUND

• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

  PMID: 39210710 BACKGROUND

MeSH Terms

Conditions

Angina Pectoris; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The randomization will be conducted in a 1:1 ratio using an internet-based randomization solution. Then, patients will be randomly assigned to either the control group or the intervention group, and regardless of study allocation and initial RF-CL assessement, all patients will then receive an initially blinded CCTA. The cardiologist conducting the CCTA is unaware of the patient's randomization status. Patients in the intervention group with a clinical likelihood of obstructive CAD (RF-CL) ≤5% will receive a blinded CCTA. Patients in the intervention group with RF-CL \>5% will undergo a CACS assessment to estimate a CACS-CL. Patients in the control group, and patients in the intervention group with a CL \>5%, will receive their test results, including unblinding of the results from the CCTA. Patients in the intervention group with CL≤5% will also receive their test results, except for the CCTA results which remain blinded. The interviewer at follow-up is unaware of the CCTA result.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The project is a randomized, multi-centre interventional study that includes patients without prior evaluation for obstructive CAD who are referred for cardiac CT based on clinically suspected stable ischemic heart disease. Participants are 1:1 randomized into either an intervention group where patient management relies on an initial CL evaluation, or a control group that adheres to current standard diagnostic procedures. This design allows for direct comparison of outcomes between the new and existing diagnostic strategies.

Study Record Dates

• First Submitted: November 13, 2024
• First Posted: November 27, 2024
• Study Start: November 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)